Welcome to our timely updates on all things SDS, Science, and Advocacy. We bring you a digest of recent scientific publications, conferences, and other newsworthy content - all relevant to SDS - with links to more details and learning opportunities. Are you interested in anything specific? Did we miss something? Let us know. Email genetics@SDSAlliance.org or message us on Facebook! This is all for you!

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SDS POPS 2024 covered a wide range to topics, from SDS patient stories, to the cosmos of research, to high impact research collaborations with the SDS Alliance

Here is a Quick recap

The meeting focused on Shwachman-Diamond Syndrome (SDS), covering patient stories, research developments, and advocacy efforts. Discussions included the importance of genetic testing, clinical trials, and drug development for SDS, as well as the challenges faced by patients and their families. The meeting also highlighted ongoing projects and collaborations aimed at improving understanding, diagnosis, and treatment of SDS, including a film project, patient surveys, and efforts to create mouse models for research.

We invite the community to help accelerate research by considering:

• participating in the SDS Patient LENS study. Indicate interest in the event feedback survey.

• filling out the event feedback survey to help improve future events (and potentially receive a signed copy of Dr. Feigenbaum's book, Chasing My Cure)

• joining the SDS-GPS program to contribute patient-reported data.

• participating in the "Million Steps Closer to Cure SDS" fundraiser starting October 25th.

• participating in the Global SDS Awareness Day and Action Week campaign from November 1-7

• FREE genetic testing for Shwachman-Diamond Syndrome. Visit our resource page or reach out to our team at genetics@sdsalliance.org for more resources and information.

  • Rare Genomes Project if they have no or inconclusive results.

• informing their healthcare providers about the new ICD-10 code for SDS (D61.02)

• sharing their genetic test results through the SDS GPS program for potential submission to ClinVar.

We shared updates on many topics, including

• SDS Alliance's continued work with Jackson Labs on developing viable humanized mouse models for SDS research.

• Dr. Dan Bauer's work towards therapeutic gene editing for SDS

• SDS Alliance to launch quality of life surveys as part of the SDS GPS program

• Our new qualitative research project: SDS Patient LENS study

• clinical trial opportunities, such as the X4 Pharma trial for chronic neutropenias

Summary

A thread throughout the meeting was our recent publication framing Shwachman-diamond Syndrome as Model Rare Disease

Session I: SDS Patient Voice and Stories

Dr. Eszter Hars, President and CEO of the Shwachman-Diamond Syndrome Alliance, led a session focused on patient voice and the importance of patient stories in understanding each other and driving research and therapy development.

• Joyce, a 16-year-old rare disease advocate, shared her personal journey with the syndrome, emphasizing the importance of advocacy and the need for governmental policy change.

• A new film project, aiming to shed light on the realities of living with SDS and to influence regulators and drug developers, was also discussed.

  • Two families, Erica and Cassie Thompson, and Amanda Jacobs, shared their experiences with SDS, highlighting the challenges of late diagnosis and the importance of genetic testing. The conversation ended with a discussion about the potential impact of the film project on the medical community and the SDS community.

  • The need for various types of research needed to develop treatments for diseases were also discussed, including clinical trials, drug repurposing efforts, therapeutic gene editing, and qualitative research.

Session II. The Cosmos of Research

• Julianne Mills (Worldwide Clinical Trials) explained the process of clinical trials, including the different phases, patient screening, and the role of regulatory agencies across countries. The presentation focused on the process of clinical trials, the importance of consent from patients and their legal representatives, and the goal of drug repurposing to save time and money while maintaining patient safety.

• Dr. Eszter Hars highlighted ClinicalTrials.gov as a resource for finding relevant clinical trials for Shwachman-Diamond Syndrome and associated symptoms.

• Drug Repurposing and AI. Dr. Feigenbaum shared his personal story of battling Castleman's disease and his subsequent discovery of an MTOR inhibitor that has kept his disease in remission for over 10 years. He co-founded EveryCure, a company aiming to unlock the full potential of FDA-approved drugs to treat various diseases and patients. He discussed the development of next-generation artificial intelligence technologies that have enabled the scaling of drug and disease analysis.

• Dr. Bauer, a principal investigator and staff physician at Dana-Farber and Boston Children's Cancer and Blood Disorder Center, discussed his work on gene therapy for Schwachman-Diamond Syndrome and the potential of genome editing technologies, specifically focusing on the use of engineered CRISPR systems.

• Dr. Vanessa Merker, a qualitative research expert, discussed the importance of qualitative research in understanding human experiences and behaviors, particularly in complex or new subjects. She emphasized the role of the FDA's Patient Focused Drug Development program in learning from this approach.

• Understanding Cancer and Rare Diseases through Natural History Studies. Dr. Sharon Savage from the Clinical Genetics branch at the National Cancer Institute discussed the importance of understanding the causes of cancer, particularly in the context of rare diseases. She explained the concept of a natural history study and its application to rare cancer-prone disorders. She also discussed the inherited bone marrow failure syndrome study, which aims to understand the spectrum of complications associated with these syndromes. She highlighted the history and evolution of understanding Dyskeratosis Congenita, a genetic disorder, and the importance of long-term follow-up studies in understanding the risks of cancer in patients with TBDS.

Session III: SDS Alliance Collaborations for Impact

Shwachman-Diamond Syndrome Developments and Research. Eszter discussed recent developments related to Shwachman-Diamond Syndrome (SDS), including a new collaboration with a tech company, the implementation of an ICD-10 code for SDS in the US, and efforts for newborn screening programs. Representatives from the Broad Institute presented on the Rare Genomes Project for genetic testing and the Genetic Prevalence Study to estimate SDS prevalence. The SDS Alliance team introduced the SDS Patient Lens Study to understand patient experiences and the SDS GPS Program (Global Patient Survey and Collaboration Program) for data collection. She also mentioned the Genome Connect patient registry, the SDS GPS program results, and upcoming events like SDS Action Week and a video on sibling research.

• Dr. Eszter Hars discussed the challenges in developing a humanized mouse model for SDS, a genetic disorder, and the ongoing strategies to overcome these challenges. She also provided a refresher on molecular biology, focusing on DNA, RNA, and the process of splicing.

• Dr. Steve Murray discussed the Jackson Laboratory's efforts to engineer a mouse model for Shwachman-Diamond syndrome (SDS) that accurately reflects the disease's key features. He highlighted the lab's expertise in creating sophisticated mouse models and their capabilities for systematic phenotypic characterization. He provided an update on the ongoing work and future plans.

• Dr. Eszter Hars introduced a second mouse model collaboration with a new technology based on iPSCs.

• Next, she focused on the SDS Alliance's strategy to contribute towards data and data infrastructure, and the importance of identifying and diagnosing patients accurately, particularly in the context of newborn screening. She also highlighted the organization's efforts to make genetic testing more accessible for patients and introduced the topic of variants of unknown significance (VUS) in genetic testing.

• Melanie O'Leary, a principal clinical genomics specialist at the Broad Institute at MIT and Harvard, then explained the Rare Genomes Project, a free and remote research-based program that performs whole genome sequencing to identify the genetic cause of rare diseases, including SDS.

• Genetic Prevalence of EFL1. Katie Russell of the Broad Institute of MIT and Harvard discussed a genetic prevalence study on the EFL1 gene related to SDS, detailing the methodology and introducing a tool called Genie for estimating prevalence. She also mentioned a project identifying pathogenic variants and returning results to the SDS Alliance.

• Ashley Thompson (Genetics Project Manager, SDS Alliance) and Grace Lynch (genetic counseling student at MGH) introduced the SDS Patient LENS Study, a collaboration with Harvard/MGH to explore SDS patients' experiences and needs, involving interviews with affected individuals or caregivers.

Some more details about the topics discussed:

• Eszter discussed the potential of Shwachman-Diamond Syndrome (SDS) as a model rare disease for drug development and the need to de-risk drug development.

• She announced plans to host an externally led patient-focused drug development meeting (EL-PFDD meeting) to help the FDA and product developers to gather patient perspectives on their condition and available therapies.

• Joyce, a 16-year-old rare disease advocate, shared her personal journey with SDS and her advocacy work, emphasizing the importance of advocacy in raising awareness about the lives of rare disease patients. Joyce also discussed her efforts to create a governmental official awareness day for SDS and her work on three bills aimed at improving access to care and streamlining insurance processes.

Raising Awareness for SDS Through Film

Eszter introduced a film project aimed at raising awareness about Shwachman-Diamond Syndrome (SDS) and its impact on families. The film, directed by Levi Gershkovich, features families sharing their personal stories.

The trailer was premiered at the meeting! Followed by a discussion with two participating families.

• Erica Thompson and Cassie Thompson shared their son Elijah's late SDS diagnosis, highlighting the need for earlier genetic testing.

• Amanda Jacobs discussed her daughter Addison's SDS diagnosis at nine months old, her severe symptoms, and the treatment she received at Children's Hospital of Philadelphia. Amanda shared her daughter Addison's medical journey, including successful treatment for a p53 mutation through a clinical trial using the chemotherapy drug Treosulfan.

• Erika, Kassi, and Amanda discussed the challenges of living with undiagnosed Shwachman-Diamond syndrome (SDS), emphasizing the need for early detection and better support. Kassi highlighted the importance of raising awareness and finding new treatments for SDS.

Do you enjoy the SDS & Science Snapshots? You can Sign up by using the button on the top right of this post:

Welcome to our timely updates on all things SDS, Science, and Advocacy. We bring you a digest of recent scientific publications, conferences, and other newsworthy content - all relevant to SDS - with links to more details and learning opportunities. Are you interested in anything specific? Did we miss something? Let us know. Email genetics@SDSAlliance.org or message us on Facebook! This is all for you!

ESH-EBMT-EHA-IPIG 3rd Translational Research Conference BONE MARROW FAILURE AND LEUKAEMIA PREDISPOSITION SYNDROMES

This month, international bone marrow failure and leukemia predisposition syndrome experts gathered in Paris for the biannual ESH-EBMT-EHA-IPIG 3rd Translational Research Conference BONE MARROW FAILURE AND LEUKAEMIA PREDISPOSITION SYNDROMES to discuss advances in the field and opportunities for progress. Dr. Hars from the SDS Alliance had the opportunity to catch up on the latest science and leading experts, many on the SDS Alliance Scientific and Medical Advisory Board.

Presentation Highlights Relevant to Shwachman-Diamond Syndrome

• Dr. Coleman Lindsley (Boston) shared an overview of the role of CHIP in allogeneic stem cell transplant and bone marrow failure, along with other international researchers covering other aspects of stem cell biology and leading to a insightful discussion.

• Dr. Lisa McReynolds (NCI, Bethesda, MD, USA) highlighted genome first approaches to uncovering leukemia etiology, complementing insights into inherited predisposition to leukemia.

• Dr. Alan Warren (Cambridge, UK) provided an overview of his work on Shwachman-Diamond Syndrome and the molecular interplay of clonal evolution in ribosomal disorders and inspired a lively discussion on the session topic.

The full program is available here.

Connecting with Shwachman-Diamond Syndrome Key Opinion Leaders

We had the opportunity to catch up with the wonderful SDS experts and key opinion leaders above, as well as with Dr. Kas Myers (Cincinnati, OH, US) regarding the North American SDS Registry's work and plans for the coming year, new opportunities to collaborate with St. Jude under Dr. Marcin Wlodarski (St. Jude, Memphis, TN, US) leadership, the work of the Inherited Bone Marrow Failure Study at the NCI (NIH) under the leadership of Dr. Sharon Savage (Bethesda, MD, US), and an exciting new startup company looking to develop new treatment options for p53 driven AML (leukemia, blood cancer).

SDS Alliance shares abstract to highlight resources

The Shwachman-Diamond Alliance submitted an abstract to this conference which was accepted and published in the conference book, titled:

FROM CHALLENGE TO OPPORTUNITY: HOW SHWACHMAN-DIAMOND SYNDROME BECAME READY FOR TRANSLATION AND A PROMISING TARGET FOR THERAPY DEVELOPMENT, AND THE ROLE OF PATIENT ADVOCACY

The objectives of this landscape analysis and strategic plan are to determine what the

challenges are to advance therapy development for Shwachman Diamond Syndrome, and how to overcome them to create new opportunities to improve patient lives.

Shwachman-Diamond Syndrome Alliance is a nonprofit research-focused patient advocacy organization that drives and accelerates therapy development focused on eliminating the leukemia risk posed by SDS. As part of this work, we surveyed the SDS research and community landscape to identify roadblocks to therapy development and developed tools and strategies to overcome them. This has led to the creation of several strategic programs.

Our work can be categorized into four categories: model system development, regulatory engagement, patient community development, and data generation and access. Specifically, in our abstract we shared updates on:

• Mouse Model System Development: We have successfully launched multiple projects to develop a functioning mouse model for SDS. The first type of model humanized the SBDS gene. Surprisingly, this turned out to be embryonic lethal. Currently, we are working with Jackson Laboratory to test multiple strategies to overcome the embryonic lethality. We are also working on iPSCs engraftment murine models with a collaborator. More details coming soon.

• US ICD-10 code for Shwachman-Diamond Syndrome. We have successfully advocated for the code, and continue its promotion. The code has now been applied to over 515 patients in the US since its implementation a year ago.

• We have created a global patient survey platform (global patient registry) to capture the lived experience of patients and caregivers as reported by them, amplify their voice and inform translational and therapy development work, and serve to connect patients with relevant clinical research and trials (recruitment support). It is IRB approved, GDPR compliant, with proper consenting workflows in place. Our pilot cohort demonstrated feasibility and it is now fully launched in 5 languages. We look forward to creating new collaborations with the translational research community.

The other wonderful meeting we had the great pleasure to attend was the:

5th National Neutropenia Day: Sharing the experience and providing better care

This is a meeting conducted by the French Neutropenia Registry by Dr. Jean Donadieu and Blandine Beaupain, every year or two, with a day for physicians and researchers, and a day for patients and all interested parties.

Part 1 focused on an overview and update from the French Neutropenia Registry

by B. Beaupain (Reference Center - APHP Trousseau, Paris).

Part 2 focused on clinical / therapeutic trials in neutropenia: alternatives to GCSF and bone marrow transplantation

• Mavorixafor in WHIM syndrome and chronic neutropenia J. Donadieu (Reference Center - APHP Trousseau, Paris)

• HPV viromes and plerixafor C. Deback, (Université Paris Saclay)

• iSGLT2: for G6PC3 and GSDIb neutropenia: French cohort and literature data J. Donadieu (Reference Center - APHP Trousseau, Paris)

• Elamipretide in Barth syndrome E. Panaioli (APHP Necker, Paris)

• Biological news on LGL leukemia C. Pastoret (Hôpital Pontchaillou, Rennes)

Part 3 focused on the genetic and functional aspects

• Contribution of exome and genome sequencing in the diagnosis of neutropenia S. Marti (APHP Pitié Salpêtrière, Paris)

• ADA2: clinical aspect, functional aspect I. Meyts (Leuven University Center)

• WHIM: Role of inflammaging in anti-infectious and vaccine responses C. Moulin (APHP Saint Louis, Paris)

• GATA2 deficiency: from somatic mutations to the indication of transplantation M. Pasquet, L. Largeaud, (Toulouse CHU and Oncopole), F. Sicre de Fontbrune (APHP St Louis, Paris)

• Functional aspects of Signal Recognition Protein anomalies L. Durix (Institut Gustave Roussy, Villejuif)

  
  

Day 2, morning session focused on questions and answers, and a short introduction and discussion with the audience

• Generalities: the Reference Center, the registry and the PNDS: a structure for 30 diseases: what's new? J. Donadieu & B. Beaupain (Reference Center - APHP Trousseau, Paris)

• Organization of diagnostic opinions in France: Multidisciplinary Consultation Meetings or how to offer relevant opinions for diagnosis and care J. Donadieu & B. Beaupain (Reference Center - APHP Trousseau, Paris)

• Organization of myeloid monitoring: common use of myeloid NGS for monitoring leukemia risk P. Hirsch (APHP Pitié-Salpêtrière, Paris)

• Improving oral dental care M. Biosse-Duplan (APHP Bretonneau)

• Alternative to GCSF: example of G6PC3 neutropenia and Glycogenosis Ib J. Donadieu (Reference Center - APHP Trousseau, Paris)

The afternoon was dedicated to breakout/ DISCUSSION GROUPS: feedback and questions

• Shwachman syndrome: various questions A. Trognon (CLINICOG, Nancy)

• Chronic neutropenia: managing daily life in adults and children: treatment, transplant and follow-up / Various questions F. Sicre (APHP St Louis), N. Aladjidi (CHU Bordeaux)

• Barth syndrome: Elamipretide: interest, perspective of care and management in the daily life of patients

The discussions in the SDS breakout room were heavily focused on the challenges adult SDS patients face when pursuing an education and career. In France, it can be very difficult to advocate for flexible schedules and other accommodations. Dr. Hars contributed an US perspective. Dr. Donadieu emphasized how very important family support is for SDS patient's success at all stages of life.

Dr. Hars prepared a presentation about the SDS-GPS program (in French!) but decided to share the recording after the meeting as to not interrupt the lively discussions.

After the meeting, Dr. Donadieu and Blandine Beaupain offered a tour through the registry. They have an impressive amount of well organized records. The French Neutropenia registry is a role model in consistent, high quality data, along with a high enrollment rate. Blandine travels to various hospitals around France to collect the records and enter them into the system. Genetic and other testing are performed in a central lab, ensuring high quality and consistency.

Do you enjoy the SDS & Science Snapshots? You can Sign up by using the button on the top right of this post:

Welcome to our timely updates on all things SDS, Science, and Advocacy. We bring you a digest of recent scientific publications, conferences, and other newsworthy content - all relevant to SDS - with links to more details and learning opportunities. Are you interested in anything specific? Did we miss something? Let us know. Email genetics@SDSAlliance.org or message us on Facebook! This is all for you!

DIY Fundraising for Shwachman-Diamond Syndrome: How You Can Fuel Research and Hope for the SDS Community!

For rare diseases like Shwachman-Diamond Syndrome (SDS), the funding landscape is often difficult. While grants and corporate donations support some research, they are rarely enough to address the breadth of medical questions researchers have. Patient-led fundraising is often a lifeline for progress, directly enabling more research, clinical trials, and potential breakthroughs.

With Giving Tuesday a little less than one month away on December 3, 2024, our team at SDS Alliance invites you to participate in DIY fundraising, so our community can help bridge the funding gap, fueling the search for new treatments and bringing hope to families affected by SDS.

Here's how you can start your own fundraising journey, get your community involved, and make a lasting impact for everyone affected by SDS.

You don’t have to be a professional fundraiser to make a big impact! Here are some simple, community-centered ways to raise funds for the SDS Alliance:

1. Host a Neighborhood Yard Sale

Gather items you no longer need and invite neighbors to join. Yard sales are great ways to declutter and raise money while involving the entire community. Have informational signs available that explain what SDS is and the importance of your fundraising efforts.

2. Cook-Off or Bake Sale

Food brings people together! A cook-off or bake sale can be a fun way to get the community involved. Ask local bakeries or restaurants to donate goods, or have friends and family contribute their best recipes. Use this opportunity to set up an information booth where people can learn about SDS and your fundraising goals.

3. Birthday Fundraisers on Social Media

Instead of traditional gifts, request donations to your fundraising page in honor of your birthday. Platforms like Facebook allow you to easily set up a fundraiser, which makes it simple for friends and family to contribute directly to the cause. This also offers a great platform to share why SDS research is so close to your heart.

4. Host an Online Auction or Raffle

An online auction or raffle allows people near and far to support your fundraising efforts. Reach out to local businesses or artisans who may be willing to donate products or services for the cause. Not only does this raise funds, but it also raises awareness among those who may not yet know about SDS.

5. Create Your Own Fundraiser

Have your own fundraising idea? Let your creativity shine and host a DIY fundraiser that is most fun for you and shows off your passion and skill sets. Whether you decide to host a game night or wine-tasting event, the sky is the limit when it comes to hosting your own DIY fundraiser. 

Sharing Your Story: The Heart of Fundraising

The most powerful aspect of DIY fundraising is the ability to share your personal connection to SDS. Whether you're a patient, a family member, or a friend of someone with SDS, sharing your unique story helps people understand why supporting the SDS Alliance is so vital and important to you. When people see the faces and hear the stories of those affected by SDS, they’re more likely to connect with the cause on a personal level.

The reality of living with SDS is not widely understood, so every story shared brings us one step closer to building a supportive and informed community that cares about rare disease research. By sharing your journey, you not only inspire others to donate but also help raise awareness for Shwachman-Diamond Syndrome on a larger scale. 

Your Impact

Every dollar raised by DIY fundraisers goes directly toward initiatives like:

• Accelerating Research: More funds mean more projects dedicated to understanding SDS and developing tools for research, which is crucial for developing new treatments and, someday, a cure.

• Clinical Trials: Funding enables developing ideas into clinical trials, giving patients the opportunity to participate in potential new treatments.

• Support for Families: The SDS Alliance provides resources and guidance for families navigating this challenging condition. Your support helps them extend these services.

  
  

Together, through DIY fundraising, sharing your story, and involving your community, you are paving the way toward a brighter future for everyone affected by SDS.

Ready to make a difference? Start your DIY fundraising journey today! Every effort counts, and together, we can create a lasting impact in the fight for a cure for SDS.

For more information, visit: https://www.sdsalliance.org/fundraise. 

Do you enjoy the SDS & Science Snapshots? You can Sign up by using the button on the top right of this post:

Welcome to our timely updates on all things SDS, Science, and Advocacy. We bring you a digest of recent scientific publications, conferences, and other newsworthy content - all relevant to SDS - with links to more details and learning opportunities. Are you interested in anything specific? Did we miss something? Let us know. Email genetics@SDSAlliance.org or message us on Facebook! This is all for you!

Understanding the Link Between Shwachman-Diamond Syndrome and Diabetes During National Diabetes Awareness Month

November is National Diabetes Awareness Month in the United States and November 14th is World Diabetes Awareness day - a time dedicated to increasing awareness about diabetes and supporting those affected by it. Incidentally, November is also Pancreatic Disease Awareness Month. This is not a co-incidence, as the cells that regulate blood sugar levels reside in the pancreas.

Diabetes is one of the most common chronic diseases in the United States. According to the CDC, approximately 38 million Americans have been diagnosed with diabetes.

While most people with SDS experience exocrine pancreatic insufficiency, which affects digestion, some also develop diabetes. Visit the SDS Alliance website for more information about symptoms of SDS.

Types of diabetes and pancreatogenic diabetes

There are several types of "diabetes". The best known include type 1 and type 2.

Different types of diabetes have different causes and mechanisms, including:

• Type 1 diabetes

  The body's immune system destroys the cells that produce insulin, resulting in little or no insulin production. This is a lifelong condition that requires constant management. 

• Type 2 diabetes

  The body may produce insulin, but the cells don't respond properly. This is the most common type of diabetes, affecting 90–95% of people with diabetes. Risk factors include genetics, being overweight, and a lack of physical activity. 

• Panreatogenic diabetes

Chronic pancreatitis, pancreatic cancer, and genetic disorders that affect the pancreas - such as Cystic Fibrosis - can also cause diabetes. This type of diabetes is called pancreatogenic diabetes. Pancreatogenic diabetes, also known as type 3c diabetes, is a type of diabetes that occurs when the pancreas is damaged, affecting its digestive and exocrine functions. It is often mistaken for type 2, which could lead to suboptimal treatment.

Diabetes and Shwachman-diamond Syndrome (SDS)

Shwachman-Diamond Syndrome (SDS) is a distinct genetic condition that often affects the pancreas, too. SDS patients may be at risk for this type of diabetes due to the pancreas having structural issues. How big this risk is is subject to current research. Other types of diabetes, including type 1, have been reported in Shwachman-Diamond Syndrome as well, and seem to occur at higher frequency in SDS patients than the general population. If you have concerns, please reach out to a qualified endocrinologist.

Our friends at Mission:Cure - a nonprofit focused on chronic pancreatitis - put together a comprehensive overview of pancreatogenic diabetes and hosted a webinar Dr. Belllin, an expert in the field. Watch it here:

Other types of diabetes, including type 1, have been reported in Shwachman-Diamond Syndrome as well, and seem to occur at higher frequency in SDS patients than the general population. Type 1 diabetes occurs when the body's immune system mistakenly destroys the insulin-producing cells in the pancreas. In SDS patients, this condition can occur at an early age, sometimes starting in infancy or early childhood. Interestingly, researchers suggest diabetes in SDS patients may have a milder course compared to typical cases of type 1 diabetes, and some may experience hypoglycemia (low blood sugar) rather than high blood sugar in the early stages. Scientists believe that the unique genetic changes in SDS might make these individuals more vulnerable to developing diabetes, either through problems with immune function or reduced insulin production. If you have concerns, please reach out to a qualified endocrinologist.

Symptoms of diabetes to watch for

According to the CDC, there are early signs of diabetes to watch for. If you have any of the following diabetes symptoms, see your doctor about getting your blood sugar tested:

• Urinate (pee) a lot, often at night

• Are very thirsty

• Lose weight without trying

• Are very hungry

• Have blurry vision

• Have numb or tingling hands or feet

• Feel very tired

• Have very dry skin

• Have sores that heal slowly

• Have more infections than usual

Be proactive when it comes to diabetes

If you or a family member has SDS, it’s essential to be proactive about blood sugar health, even if diabetes hasn’t been diagnosed. Regular check-ups with your doctor can help monitor blood sugar levels and catch any early signs of diabetes. Early detection is important, as it can lead to better management strategies, including lifestyle adjustments and, if needed, medications or insulin. Your healthcare provider may recommend regular blood sugar testing, particularly if any symptoms like increased thirst, frequent urination, or unexplained weight loss appear.

Staying healthy with SDS and managing any potential diabetes risk involves more than just monitoring blood sugar levels. Research recommends following a balanced diet with a focus on low-glycemic foods (foods that don’t cause rapid spikes in blood sugar) that can support steady blood sugar levels. For those who have already been diagnosed with diabetes, insulin therapy may be necessary, and some patients have found that insulin pumps help manage their blood sugar more effectively. Exercise and hydration can also make a big difference in maintaining health.

National Diabetes Awareness Month is a reminder to the SDS community that early action and a proactive approach to health can make a significant difference. If you’re part of the SDS community, talk to your healthcare provider about how you can keep your blood sugar levels in a healthy range and what steps are most helpful for managing or preventing diabetes. Together, we can spread awareness and support each other in staying as healthy as possible.

Talk with your doctor about making a diabetes care plan this National Diabetes Month. Managing diabetes as soon as possible after diagnosis can help prevent serious health problems. Learn more from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)!

For more information and resources about living with type 1 diabetes, visit the website of Breakthrough T1D (formerly JDRF). This website is also available in Spanish!

Disclaimer: This blog post is intended for informational purposes only and is not a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of a qualified healthcare provider with any questions you may have regarding a medical condition or treatment. Never disregard professional medical advice or delay seeking it because of something you have read in this post.

Do you enjoy the SDS & Science Snapshots? You can Sign up by using the button on the top right of this post:

Welcome to our timely updates on all things SDS, Science, and Advocacy. We bring you a digest of recent scientific publications, conferences, and other newsworthy content - all relevant to SDS - with links to more details and learning opportunities. Are you interested in anything specific? Did we miss something? Let us know. Email genetics@SDSAlliance.org or message us on Facebook! This is all for you!

SDS Alliance is Energized by the Annual CZI Science in Society Meeting

With yesterday’s launch of Global Shwachman-Diamond Syndrome (SDS) Awareness Day and Action Week (1-7 November), our team at SDS Alliance is reflecting on our recent experience at the invitation-only Annual Science in Society (SiS) Meeting hosted by the Chan Zuckerberg Initiative (CZI) which brought together the CZI Rare As One (RAO) network, a passionate community of rare disease patients and caregivers, patient advocacy group leaders, scientists, clinicians, and policymakers, committed to advancing rare disease research and improving patient outcomes. The SDS Alliance was Awarded a transformational Chan Zuckerberg Initiative “Rare As One” Grant in 2021, as part of cycle 2.

The first full meeting day (16 October 2024) themed, “Accelerating Rare Disease Diagnosis,” was focused on shortening the diagnostic journey that many families face. Currently, it can take six years or more for patients with rare diseases to receive an accurate diagnosis. Experts and leaders from across the rare disease community challenged each other to envision cutting this time to just six weeks within the next six years. Discussions included emerging tools like artificial intelligence (AI) that could support real-time diagnostics, ways to better understand variants of uncertain significance, and policies to make diagnostic resources widely accessible. For the SDS Alliance team, attending this meeting was energizing, reaffirming the importance of equitable diagnostic access and showing promise for a future where SDS patients may face fewer hurdles on their diagnostic journeys.

The second meeting day (17 October 2024), centered on “Data Integration for Disease Characterization” and “Impact,” brought attention to the incredible potential of patient data to propel rare disease research forward. Speakers presented innovative registries and platforms for collecting data that can characterize diseases in greater detail and support the development of new treatments. A big focus was also on making data gathering accessible and patient-centered, envisioning technologies like wearables to track health in real-time. This session was particularly insightful for the SDS Alliance team in light of our recent launch of the SDS Global Patient Survey and Collaboration Program: SDS-GPS (learn more about the GPS Program and how to make your voice count here!).

Finally, leaders from patient-driven organizations shared successes and discussed novel funding models to advance research, offering a roadmap for how patient communities, like those affected by SDS, can contribute to and benefit from advancements in rare disease research and treatment development. 

Not only did the CZI SiS meeting provide the opportunity for SDS Alliance team members Ashley Ferreira (pictured on the right below) and myself (Ashley Thompson, as seen on the left) to meet in person for the first time, but it also underscored that meaningful progress for advancing diagnostics and therapeutics for the SDS community is within reach, giving SDS Alliance new ideas and a renewed sense of purpose in our advocacy and research efforts.

This was the first CZI SiS meeting Ashley Ferreira had the opportunity to attend in-person. She was kind enough to write up and share her thoughts and reflections about attending this meeting and engaging with the RAO network below.

Attending the 2024 CZI SiS Meeting was an inspiring opportunity that deepened my understanding of the intersection of AI, healthcare, and research. The atmosphere was electric, filled with innovators and thought leaders passionate about harnessing technology for the benefit of our rare disease communities. There were various sessions that offered valuable insights into how AI is transforming the landscape of healthcare, from pre-clinical research to personalized patient care.

One of the highlights was the discussion on AI-driven predictive analytics in patient care. Experts shared case studies demonstrating how machine learning models can analyze vast datasets to identify at-risk patients before issues arise, ultimately leading to better health outcomes. The emphasis on collaboration between data scientists and medical professionals underscored the importance of interdisciplinary approaches in developing effective AI tools. 

Panelists also engaged in meaningful dialogue about ensuring that systems are equitable and transparent, highlighting the need for diverse datasets to advance research in rare disease communities effectively. By leveraging advanced algorithms and machine learning, researchers can now analyze vast amounts of genetic, clinical, and demographic data more efficiently than ever before. This capability allows for the identification of patterns and potential biomarkers that were previously difficult to discern, accelerating the discovery of effective treatments. Additionally, AI-powered tools facilitate the management of patient registries, enabling more accurate tracking of patient outcomes and experiences. This holistic approach not only fosters collaboration among researchers but also empowers patients and advocates to contribute to the knowledge base, ultimately driving progress in understanding and treating rare diseases.

Do you enjoy the SDS & Science Snapshots? You can Sign up by using the button on the top right of this post:

Welcome to our timely updates on all things SDS, Science, and Advocacy. We bring you a digest of recent scientific publications, conferences, and other newsworthy content - all relevant to SDS - with links to more details and learning opportunities. Are you interested in anything specific? Did we miss something? Let us know. Email genetics@SDSAlliance.org or message us on Facebook! This is all for you!

Shwachman-Diamond Syndrome community and impact with the 2024 Million Steps Closer to #CureSDS fundraiser

The Event for You, Your Friends, Family, and Colleagues to Have Fun and Support Research.

The Million Steps Closer to #CureSDS annual fundraiser took place October 25-31, 2024.

Anywhere (Virtual or Local if You Choose). Shwachman-Diamond Syndrome is global.

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This year, we hosted the 5th annual "Million Steps Closer" fun-run challenge fundraiser, a virtual event every October. Participants turned hope into action and took steps to #CureSDS - we could walk, run, crawl, roll, swim, or lean back and support those who do by making a donation. The steps (and fitness) counting challenges were managed through a free app and are optional.

The Purpose: To Support Research!​​​

This fundraiser is a fun and uplifting way to join us and make a difference. As always, 100% of funds raised from the community go to SDS research and infrastructure to accelerate therapy development, following our roadmap. By participating in this event, you are playing an integral part in driving progress!

Roadmap

Teams Amplify Impact!

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Participants invite family, friends, neighbors, colleagues, or classmates to participate! Registration is free! It's easily invite others to join in your fundraising efforts! Get in the spirit for next year!

Overall community goal: A million steps or more!

This year, once again, we had a small but committed and dedicates community step up to the challenge.

• 4 teams and

• 17 participants took

• an impressive total of 1,004,878 steps together

Thank you everyone who stepped up and had fun with us, while meeting critical fundraising goals for research! See you again next year!

And the 2024 Challenge Winners are:

• Laszlo H: Most Steps taken as an individual: 94,709 steps

• Team Joyce: Most Steps taken as a team: 353,933 steps

• Team Declan: Most Funds Raised as a team: $13,864 with this fundraiser and a charity hockey game in the spring.

Community and Fundraising

This event is impactful for both coming together as a community that can support each other, and also as a powerful driving force for research funding. The SDS Alliance is proud to host this event every year.

These themes are also carried forward in the inaugural

Global SDS Awareness Day is November 7th

and leading up to it,

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Global SDS ACTION Week is November 1-7th

campaigns.

Take Action to Make an Impact!

Here is a list of simple actions you can take, one or two a day during Global SDS Action Week - or anytime throughout the year. Click on the list to download a PDF with clickable links. How will you take action this year?

The Role of SDS Alliance

We at the SDS Alliance are not only passionate to raise awareness about SDS, patient's unmet needs, and our drive for progress, but we are equally if not more passionate about creating opportunities for YOU to make a difference.

Conclusion

Shwachman-Diamond Syndrome is a complex genetic disorder that requires coordinate care, caring community support, and strategic investment into research and research infrastructure to de-risk therapy development. Organizations like Shwachman-Diamond Syndrome Alliance (SDS Alliance) play a crucial role in providing support and resources for those affected and the SDS community at large. Join us and raise awareness to help others learn about this important condition.

For more information, visit SDS Alliance and join a community dedicated to improving the lives of those impacted by Shwachman-Diamond Syndrome.

Do you enjoy the SDS & Science Snapshots? You can Sign up by using the button on the top right of this post:

Welcome to our timely updates on all things SDS, Science, and Advocacy. We bring you a digest of recent scientific publications, conferences, and other newsworthy content - all relevant to SDS - with links to more details and learning opportunities. Are you interested in anything specific? Did we miss something? Let us know. Email genetics@SDSAlliance.org or message us on Facebook! This is all for you!

What is Shwachman-Diamond Syndrome Global SDS Awareness Day and Action Week?

Global SDS Awareness Day and Action Week is about coming together and raising awareness as a united global patient community.

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In 2020, the SDS Alliance reached out to all the international SDS patient organizations to discuss the idea of creating an annual Global SDS Awareness event, proposing a time in spring or fall to avoid the busy winter holiday and summer vacation seasons. Our colleagues at SDS UK proposed late April as the time to coincide with Dr. Shwachman's birthday. All organizations that responded - including SDS UK, SDS Netherlands, and SDS Foundation (US) - supported this concept and timing, and so Global SDS Awareness Week was born.​​

​Over the years, the event has not reached its full potential, so we set out to reconsider the date. We polled the international patient community for a new date/frame preference. You voted and we listened!

​Based on your feedback, the new date(s) are:

Global SDS Awareness Day is November 7th

and leading up to it,

​

Global SDS ACTION Week is November 1-7th

Take Action to Make an Impact!

Here is a list of simple actions you can take, one or two a day during Global SDS Action Week - or anytime throughout the year. Click on the list to download a PDF with clickable links. How will you take action this year?

New!

Share a vocal video!

We partnered with Vocal Video to bring you a super easy way to share your voice by answering a few simple questions. See an example (Eszter's video) on the SDS Alliance webpage for Awareness Week.

Click here or below to share your voice, today!

We will use your videos to raise awareness about SDS and to inform our programs to best support your needs!

Why was November chosen for SDS Awareness?

Dr. Shwachman was a prominent gastroenterologist in Boston in the 1960s and developed deep expertise in caring for Cystic Fibrosis (CF) patients and "atypical" CF patients. This was before SDS was recognized as a distinct disorder, and many patients were categorized as "atypical CF." Drs. Shwachman and Diamond, as well as Dr. Bodian, were instrumental in defining Shwachman-Diamond Syndrome. A landmark publication in the journal Pediatrics in 1964, entitled "The Syndrome of Pancreatic Insufficiency and Bone Marrow Dysfunction" was published by Drs. Shwachman and Diamond in November 1964. It is due to this publication that the disease received its name, "Shwachman-Diamond Syndrome". About 40 years later, Dr. Johanna Rommens and her team at SickKids in Toronto, Canada, identified the main gene responsible for SDS. The gene (and corresponding protein) was named SBDS for Shwachman-Bodian-Diamond Syndrome to acknowledge Dr. Bodian's contribution to the field. Coincidentally, the SBDS gene happens to be located on section 11 or Chromosome 7, giving a nod to the date of 11.7 or November 7.

​New SDS Awareness T-shirt Designs Now Live!

Click on the design to order. 

• Multiple colors and styles are available, including t-shirts, hoodies, and tank tops.

• International shipping is available.

• If you would like to have them printed locally in your country or community, email us at connect@sdsalliance.org and we will be happy to share the design file!

  
  

  

  

  
  

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Why participate in SDS Awareness Day and Action Week?

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It is our hope that more and more organizations and families will participate over time so that this campaign can grow and reach more families, medical providers, and researchers. We have reached out to all international SDS patient groups to invite them.

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Raising awareness can save lives. Any diagnosis made sooner lessens the burden and suffering of the diagnostic odyssey, and life-saving interventions can begin sooner. The SDS community can grow to support more targeted research, accelerating the pace toward therapies and cures.

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SDS Story Series

Huge thanks to all the SDS families from around the world for sharing their stories!

The stories are available on the SDS Alliance social media channels:

• SDS Alliance Website blog (Patient Stories)

• SDS Alliance Facebook page

The Role of SDS Alliance

We at the SDS Alliance are not only passionate to raise awareness about SDS, patient's unmet needs, and our drive for progress, but we are equally if not more passionate about creating opportunities for YOU to make a difference.

The Action Checklist on top of this post is an easy way for you to get started and take action that matters. Together, we can move mountains.

We created many resources to set you up for success. Check out the media section of our website for free downloads.

Why Community Matters

Being part of a community provides emotional support and access to the latest research and treatment options. SDS Alliance advocates for awareness, research funding, and educational resources that can greatly enhance the quality of life for those affected by SDS.

Conclusion

Shwachman-Diamond Syndrome is a complex genetic disorder that requires coordinate care, caring community support, and strategic investment into research and research infrastructure to de-risk therapy development. Organizations like Shwachman-Diamond Syndrome Alliance (SDS Alliance) play a crucial role in providing support and resources for those affected and the SDS community at large. Join us and raise awareness to help others learn about this important condition.

For more information, visit SDS Alliance and join a community dedicated to improving the lives of those impacted by Shwachman-Diamond Syndrome.

Do you enjoy the SDS & Science Snapshots? You can Sign up by using the button on the top right of this post:

Welcome to our timely updates on all things SDS, Science, and Advocacy. We bring you a digest of recent scientific publications, conferences, and other newsworthy content - all relevant to SDS - with links to more details and learning opportunities. Are you interested in anything specific? Did we miss something? Let us know. Email genetics@SDSAlliance.org or message us on Facebook! This is all for you!

Shwachman-Diamond Syndrome Alliance (SDS Alliance) shares ideas at new FDA Rare Disease Innovation Hub kick-off Meeting. FDA leaders launch rare disease hub to increase cross-center collaboration.

It was an incredible opportunity for the SDS Alliance to represent the SDS community at the FDA for the public kick-off meeting of the new Rare Disease Innovation Hub!  Advocacy with Impact. Thank you to the Reagan-Udall Foundation for the FDA for organizing the meeting and making it possible for many rare disease organizations and advocates to be heard. The day was filled with insights from passionate stakeholders, advocates, and members of the rare disease community. FDA officials, including the directors of CBER and CDER, launched a rare disease innovation hub at a public meeting on October 16, 2024, aiming to enhance collaboration and communication across the two centers and externally, to serve as a single point of entry to engage with FDA, and to streamline and accelerate therapy development for rare diseases.

The meeting was organized by the Reagan-Udall Foundation for the FDA.

The Reagan-Udall Foundation for the FDA, in collaboration with FDA’s Rare Disease Innovation Hub, hosted a public meeting on October 16, 2024. The meeting brought together rare disease patient advocates, academic researchers, regulated industry, and other key stakeholders to discuss how the recently announced Rare Disease Innovation Hub can best engage with members of the rare disease community and prioritize its work.

During this public meeting, FDA sought to gather public comment in the following areas:

• Cross-cutting rare disease-related, scientific, regulatory, or policy issues (those not related to a particular disease or condition) that should be prioritized for consideration by the Rare Disease Innovation Hub

• Rare disease-specific (but not application-specific) scientific, regulatory, or policy issues that should be prioritized for consideration by the Rare Disease Innovation Hub

• Rare disease-related activities or initiatives currently being undertaken independently by CDER or CBER that you believe would benefit from being undertaken by the Rare Disease Innovation Hub as a joint activity

• Approaches that the Rare Disease Innovation Hub should follow for engagement with patients and caregiver groups, industry organizations, and scientific/academic organizations

  
  

In addition to the presentations during the hybrid meeting, comments can be submitted to the docket by October 31st as described in the Federal Register Notice.

The full meeting recording is now available on the meeting page and on YouTube, here:

Endpoints News summarizes the event in their recent article:

The hub will work across different rare diseases, the vast majority of which do not have any treatment. The FDA said it will “particularly focus on products intended for smaller populations” or for diseases in which the natural history is not well understood. The hub “will bring us the coordination between the centers that I think will really make sure that things like biomarkers are coordinated,” Marks said in his introductory remarks. He added that CDER and CBER reporting structures won’t be disrupted but there will be more collaboration. CDER Director Patrizia Cavazzoni highlighted that this meeting already demonstrates how the hub “will turbo-charge our activities across centers. We really want to listen.” At the same time, they emphasized that they are in startup mode. Dynamic, strategic, AND still looking for a director to lead the effort.

“There will be differences between gene therapies and protein therapeutics and small molecules,” Marks said. “That may mean that sometimes an endpoint or policy may have to be different, but again, we’re committed to being transparent about this.”

The remainder of the meeting included 41 speakers — from patient groups to industry — including Shwachman-Diamond Syndrome Alliance's President and CEO Dr. Eszter Hars, discussing everything from the rare diseases of their children to ways that the FDA can be more nimble. The agency said it received more than 200 requests to participate in the meeting.

Some speakers sought improved consistencies across the FDA drug and biologic centers, citing the need to establish regular and transparent lines of communication with sponsors. Others requested a roadmap for the hub’s short and long-term goals. Comments on the docket are still open, according to the FDA. Dr. Hars highlighted the need of the SDS and many other rare disease communities to collaborate with the FDA, researchers, and other stakeholders to support the development of biomarkers and outcome measures, which could support the development of new therapies using different modalities and could accelerate the work and impact across multiple agencies.

More about the Rare Disease Innovation Hub from the meeting organizers and its impact on SDS Alliance's mission

"An estimated 10,000+ rare diseases affect more than 30 million people – approximately one out of every 10 people – in the United States, and about half of these people are children. While there have been important advances in treatments for rare diseases, more needs to be done. Many rare diseases lack treatment options and therefore many patients have high unmet medical needs. This requires new approaches to expedite development and approval of safe and effective drugs and biologics. The FDA sees huge potential in establishing a new model, within the FDA, to leverage cross-agency expertise and greatly enhance our inter-center connectivity to spur the development of treatments for rare diseases.

To that end, the Center for Biologics Evaluation and Research (CBER) and the Center for Drug Evaluation and Research (CDER) are launching a Rare Disease Innovation Hub to advance rare disease therapy development through greater communication, collaboration, and coordination across CBER and CDER, in coordination with other Centers and Offices across FDA. Helmed by senior leadership from CBER and CDER, the Hub will work to develop and implement a comprehensive cross-center rare disease strategic agenda that takes full advantage of our current clinical and scientific expertise across both centers and is based on a shared vision and comprehensive approach to 1) align methods and approaches to rare disease programs, both during IND development, and in application review; 2) identify and enable innovative approaches in the areas of novel endpoints, biomarker development, and innovative trial designs; and 3) streamline communications with the rare disease community. The Hub will work across rare diseases but will especially focus on products intended for smaller populations or for diseases where the natural history is variable and not fully understood, as we recognize that development of therapies for these conditions can be particularly challenging."

This gives us at the SDS Alliance reasons for hope and momentum to implement our strategies to no only make therapy development possible, but fast and likely.

The Role of SDS Alliance

Organizations like SDS Alliance provide vital support for individuals and families affected by Shwachman-Diamond Syndrome, in particular offering access to information on the latest research and foundational understanding of the basics of research participation. They offer resources, connect patients with medical experts and researcher, and foster a community where individuals can share experiences and information and turn hope into action, together.

Why Community Matters

Being part of a community provides emotional support and access to the latest research and treatment options. SDS Alliance advocates for awareness, research funding, and educational resources that can greatly enhance the quality of life for those affected by SDS.

Conclusion

Shwachman-Diamond Syndrome is a complex genetic disorder that requires coordinate care, caring community support, and strategic investment into research and research infrastructure to de-risk therapy development. Organizations like Shwachman-Diamond Syndrome Alliance (SDS Alliance) play a crucial role in providing support and resources for those affected and the SDS community at large. Join us and raise awareness to help others learn about this important condition.

For more information, visit SDS Alliance and join a community dedicated to improving the lives of those impacted by Shwachman-Diamond Syndrome.

Do you enjoy the SDS & Science Snapshots? You can Sign up by using the button on the top right of this post:

Welcome to our timely updates on all things SDS, Science, and Advocacy. We bring you a digest of recent scientific publications, conferences, and other newsworthy content - all relevant to SDS - with links to more details and learning opportunities. Are you interested in anything specific? Did we miss something? Let us know. Email genetics@SDSAlliance.org or message us on Facebook! This is all for you!

Embracing Diversity in SDS: Reflecting on Hispanic Heritage Month

Every year, from September 15 to October 15, we celebrate Hispanic Heritage Month in the United States. It’s a time to recognize the histories, cultures, and contributions of Hispanic and Latino Americans. But beyond the celebration, it’s also a chance to reflect on how important it is for everyone, no matter their background, to be included in healthcare and research. At SDS Alliance, we recognize that our community is diverse, and we are committed to engaging with our global community to accelerate progress towards improved treatments and outcomes with SDS across the world.

That is why we made the investment to offer the SDS-GPS program in five languages, including Spanish. Join today!

Rare diseases, like Shwachman-Diamond Syndrome (SDS), affect a small number of people, which means that global efforts to involve individuals from diverse backgrounds in research and awareness are critical. Cases of SDS have been reported in individuals with Hispanic heritage, including one 14-year-old female and a 3-year-old male. Many families from diverse backgrounds who are affected by rare diseases like SDS may not have the same access to healthcare or opportunities to participate in research as others. Language barriers, lack of resources, and cultural differences can create challenges. That’s why Hispanic Heritage Month is a perfect time to focus on ensuring that the Hispanic community is included and supported in rare disease research. 

For families dealing with SDS, participating in research can help improve the understanding of this condition and lead to better treatments and care. It’s important to know that research studies need input from all backgrounds to get a complete picture of how rare diseases affect people differently. A perfect example of the importance of including individuals from diverse backgrounds in clinical research includes this case series, which is one of the first to describe the EFL1 gene, a rare gene known to cause an SDS-like condition, in multiple individuals from various diverse backgrounds including two siblings with Mexican ancestry. This is why it’s crucial to raise awareness about the importance of diversity in rare disease research, so that everyone—no matter their ethnicity—can benefit from advances in medical care.

At Shwachman-Diamond Syndrome Alliance, we recognize that our community is diverse, encompassing individuals of various racial, ethnic, and cultural backgrounds from around the world, and we believe that everyone's voice deserves to be heard. Hispanic Heritage Month reminds us that every culture and community brings value to the conversation, and by actively working together and engaging with our diverse global community, SDS Alliance aims to accelerate progress toward improved treatments and outcomes for individuals with SDS across the world. Together, let's continue to champion diversity and inclusivity in clinical research, ensuring that everyone has access to equitable and effective healthcare.

The website for the National Organization for Rare Diseases (NORD) is available in Spanish and so are many of their resources!

Check out the EveryLife Foundation for Rare Diseases Rare Diversity Hub for information about current efforts to increase diversity in clinical research and learn how you can get involved!

En este número: ¿Por qué es importante la diversidad en la investigación de enfermedades raras?

Abrazando la diversidad en SDS: Reflexionando sobre el Mes de la Herencia Hispana

Cada año, del 15 de septiembre al 15 de octubre, celebramos el Mes de la Herencia Hispana en Estados Unidos. Es un momento para reconocer las historias, culturas y contribuciones de los hispanos y latinoamericanos. Pero más allá de la celebración, también es una oportunidad para reflexionar sobre lo importante que es para todos, sin importar su origen, estar incluidos en la atención sanitaria y la investigación. En SDS Alliance, reconocemos que nuestra comunidad es diversa y estamos comprometidos a colaborar con nuestra comunidad global para acelerar el progreso hacia mejores tratamientos y resultados con SDS en todo el mundo.

Por eso hicimos la inversión para ofrecer el programa SDS-GPS en cinco idiomas, incluido el español. ¡Únete hoy!

Las enfermedades raras, como el síndrome de Shwachman-Diamond (SDS), afectan a un pequeño número de personas, lo que significa que los esfuerzos globales para involucrar a personas de diversos orígenes en la investigación y la concientización son fundamentales. Se han informado casos de SDS en personas de ascendencia hispana, incluida una niña de 14 años y un niño de 3 años. Es posible que muchas familias de diversos orígenes que se ven afectadas por enfermedades raras como el SDS no tengan el mismo acceso a la atención médica ni las mismas oportunidades para participar en investigaciones que otras. Las barreras lingüísticas, la falta de recursos y las diferencias culturales pueden crear desafíos. Es por eso que el Mes de la Herencia Hispana es un momento perfecto para centrarse en garantizar que la comunidad hispana sea incluida y apoyada en la investigación de enfermedades raras.

Para las familias que padecen SDS, participar en la investigación puede ayudar a mejorar la comprensión de esta afección y conducir a mejores tratamientos y atención. Es importante saber que los estudios de investigación necesitan aportaciones de todos los orígenes para obtener una imagen completa de cómo las enfermedades raras afectan a las personas de manera diferente. Un ejemplo perfecto de la importancia de incluir personas de diversos orígenes en la investigación clínica incluye esta serie de casos, que es una de las primeras en describir el gen EFL1, un gen raro que se sabe que causa una afección similar al SDS, en múltiples personas de diversas procedencias. orígenes que incluyen dos hermanos con ascendencia mexicana. Por eso es crucial crear conciencia sobre la importancia de la diversidad en la investigación de enfermedades raras, para que todos, sin importar su origen étnico, puedan beneficiarse de los avances en la atención médica. 

En la Alianza del Síndrome de Shwachman-Diamond, reconocemos que nuestra comunidad es diversa y abarca personas de diversos orígenes raciales, étnicos y culturales de todo el mundo, y creemos que la voz de todos merece ser escuchada. El Mes de la Herencia Hispana nos recuerda que cada cultura y comunidad aporta valor a la conversación y, al trabajar juntos e interactuar activamente con nuestra diversa comunidad global, la SDS Alliance tiene como objetivo acelerar el progreso hacia mejores tratamientos y resultados para las personas con SDS en todo el mundo. Juntos, sigamos defendiendo la diversidad y la inclusión en la investigación clínica, garantizando que todos tengan acceso a una atención sanitaria equitativa y eficaz.

¡El sitio web de la Organización Nacional de Enfermedades Raras (NORD) está disponible en español y también lo están muchos de sus recursos!

Consulte el Centro de Diversidad Rara de la Fundación EveryLife para Enfermedades Raras para obtener información sobre los esfuerzos actuales para aumentar la diversidad en la investigación clínica y aprenda cómo puede participar.

Do you enjoy the SDS & Science Snapshots? You can Sign up by using the button on the top right of this post:

Welcome to our timely updates on all things SDS, Science, and Advocacy. We bring you a digest of recent scientific publications, conferences, and other newsworthy content - all relevant to SDS - with links to more details and learning opportunities. Are you interested in anything specific? Did we miss something? Let us know. Email genetics@SDSAlliance.org or message us on Facebook! This is all for you!

How To Interpret Genetic Variants and Their Role in Health

In this week’s SDS & Science Snapshot, we are highlight some of the important work of GenomeConnect. GenomeConnect is part of the Clinical Genome Resource (ClinGen), an NIH funded research project. GenomeConnect is a registry that helps you share your genetic and health information. Sharing this information will help increase our understanding of how genes affect health. A team member from GenomeConnect will be presenting at the upcoming SDS Alliance Global Patient Advocacy and Partnering Summit (POPS) hosted virtually on Sunday, October 20 at 1 PM EDT. Register and see the details on the SDS-POPS event page, here!

In GenomeConnect’s recent newsletter, they published an infographic summarizing the process of detecting a genetic change (or “variant”) with genetic testing and then determining if the detected variant(s) impact health and disease-risk through a process known as “variant classification.” We have discussed the role of inherited (or germline) genetic variants in previous SDS & Science Snapshots. The infographic and discussion below provides additional information about the variant classification process.

During the variant interpretation process, experts ask important questions like:

• Have scientists studied this variant in a lab to see what it does?

• Was the variant inherited from a parent?

• Are there similar variants that have been studied before?

• Is this variant common in the general population?

• Has it been found in anyone who shows symptoms?

• And finally, what does the variant do to the protein it affects?

Everyone has variants in their genome – some impact health, while others do not. These genetic variants are part of the differences that make us all unique and there are different levels of classification for variants detected with genetic testing: 

• Benign and likely benign (B/LB) variants are not (or are likely not) related to disease and are not expected to cause health problems. Some genetic testing laboratories report B/LB variants, while others do not since they are genetic changes that are not anticipated to impact your health. 

• A genetic change classified as a variant of uncertain significance (VUS) is more of gray area — experts aren’t sure yet if it’s related to disease or not.

• Pathogenic and likely pathogenic (P/LP) variants are definitively (or likely) related to disease and health. Genetic testing results are often considered “positive” if one or more P/LP variants are detected.

Over time, as scientists do more research and more people undergo genetic testing, variants, especially VUSs, may be reclassified if new information becomes available. If you have had genetic testing, GenomeConnect encourages you to periodically check-in with the healthcare provider who ordered your genetic testing (or the genetic testing laboratory directly) to see if there have been any updates to the classification of a variant (or variants) previously detected that may impact your care. Plus, when you participate in the SDS-GPS program, you can opt-in to receive updates if we learn about changes to classifications.

Watch the YouTube video below published by GenomeConnect to learn more about the variant classification process and explore GenomeConnect’s YouTube playlist for more videos about genetics, genetic testing, how to read a genetic report, and more!

For more information regarding the genetics of SDS specifically, you can watch this video published by SDS Alliance.

Do you enjoy the SDS & Science Snapshots? You can Sign up by using the button on the top right of this post:

Welcome to our timely updates on all things SDS, Science, and Advocacy. We bring you a digest of recent scientific publications, conferences, and other newsworthy content - all relevant to SDS - with links to more details and learning opportunities. Are you interested in anything specific? Did we miss something? Let us know. Email genetics@SDSAlliance.org or message us on Facebook! This is all for you!

Honoring Childhood Cancer Awareness Month: A Message to the SDS Community

As September comes to a close, we at the Shwachman-Diamond Syndrome Alliance want to take a moment to acknowledge Childhood Cancer Awareness Month. This month serves as a crucial time to honor the children and families affected by pediatric cancer, including those in our own Shwachman-Diamond Syndrome (SDS) community. It’s a time to remember that behind every statistic, there is a child, a family, and a network of supporters facing unimaginable challenges. Together, we raise awareness, advocate for research funding, and educate others about the importance of early detection.

SDS brings with it unique risks, including a higher likelihood of developing certain cancers, such as myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), as well as possibly solid tumors. These cancers can develop at younger ages in people with SDS compared to the general population, making vigilance and proactive healthcare essential. This is why individuals with SDS follow special healthcare guidelines, including regular bone marrow surveillance and other screenings, to detect cancer early and take swift action when needed. By following these guidelines, we can help protect our children and provide the best possible care.

Our team at SDS Alliance also wants to take this time to express our gratitude to the medical providers, researchers, and caregivers dedicated to supporting our SDS community. The ongoing research into SDS and its relationship to childhood cancer is vital in our fight to improve treatments and work towards prevention. Awareness months like this one play an important role in highlighting the need for continued research funding and support for families navigating these complex health challenges.

While September may be coming to an end, the commitment of SDS Alliance to advocating for those with SDS and cancer risk does not stop. Let’s continue to support each other, raise our voices, and spread awareness about the impact of childhood cancer on our community. Every effort brings us one step closer to better outcomes, and with the strength of the SDS community, we can keep pushing forward for a brighter future.

Download our graphic or share from our original Facebook post by visiting our Media resource page at www.SDSAlliance.org/media.

Visit the SDS Alliance website for more information about the signs and symptoms of SDS and SDS Diagnosis and Treatment Guidelines.

Do you enjoy the SDS & Science Snapshots? You can Sign up by using the button on the top right of this post:

Welcome to our timely updates on all things SDS, Science, and Advocacy. We bring you a digest of recent scientific publications, conferences, and other newsworthy content - all relevant to SDS - with links to more details and learning opportunities. Are you interested in anything specific? Did we miss something? Let us know. Email genetics@SDSAlliance.org or message us on Facebook! This is all for you!

New Case Report: Managing Solid Tumors in SDS - Challenges and Treatment Strategies

As frequently discussed in the Shwachman-Diamond Syndrome (SDS) community, some individuals with SDS develop serious blood cancers, like leukemia, during their lifetime. Solid tumors, like breast cancer, are less common in individuals with SDS but can still happen. In this week’s SDS & Science Snapshot, we are highlighting a recently published article which shares the story of an adult woman with SDS who was successfully treated for stage IV breast cancer using a combination of chemotherapy and supportive care.

The patient, a 41-year-old woman, had SDS and developed a type of breast cancer that was hormone receptor-positive and HER2-positive. This means that the cancer was driven by specific hormones and proteins, which made it treatable with targeted therapies. Because of her SDS and underlying bone marrow issues, her doctors had to carefully adjust her treatment plan to avoid making her bone marrow problems worse. She was treated with chemotherapy drugs along with granulocyte colony-stimulating factor (G-CSF) to help her body make more white blood cells and reduce the risk of infections. After nine cycles of treatment, she achieved a complete response, meaning no cancer was detected.

Treating solid tumors like breast cancer in patients with SDS can be particularly challenging because of their underlying bone marrow problems and increased sensitivity to chemotherapy. Many SDS patients have low levels of important blood cells (i.e. neutrophils), which makes it difficult to handle standard chemotherapy. Chemotherapy can further lower these blood cell counts, increasing the risk of severe infections and other complications. The use of G-CSF, which helps the bone marrow produce more white blood cells, can be helpful but comes with its own risks. In some cases, G-CSF might increase the chance of developing leukemia in patients with SDS, especially those with certain acquired (or somatic) genetic mutations. This risk in not well established and subject to controversy in the medical community. In any case, careful monitoring is needed to balance the benefits of cancer treatment with the potential risks.

In this case, the patient was able to tolerate chemotherapy with the help of G-CSF, and her cancer responded well to treatment. However, she will need to be closely watched for any signs of blood cancers in the future, as the long-term effects of G-CSF use in SDS patients are not fully understood. For patients with SDS who develop solid tumors, it’s important to have a personalized treatment plan that takes into account these unique health challenges. Collaboration with SDS experts ins highly encouraged.

Overall, this case highlights the possibility of successfully treating solid tumors in patients with SDS, but it also emphasizes the need for careful management of their underlying blood disorders. While this patient had a positive outcome, ongoing research and close follow-up are essential for understanding the best ways to treat cancer in this rare group of patients.

We have reached out to the authors to offer our resources and support to the patient.

Morecroft R, Logothetics CN, Tarnawsky SP, Davis AA. Chemotherapy-induced neutropenia management in a patient with metastatic breast cancer and Shwachman-Diamond syndrome (SDS): a case report. Transl Breast Cancer Res. 2024 Jul 22;5:26. PMID: 39184925.

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Welcome to our timely updates on all things SDS, Science, and Advocacy. We bring you a digest of recent scientific publications, conferences, and other newsworthy content - all relevant to SDS - with links to more details and learning opportunities. Are you interested in anything specific? Did we miss something? Let us know. Email genetics@SDSAlliance.org or message us on Facebook! This is all for you!

Understanding Shwachman-Diamond Syndrome Through Zebrafish Research

Shwachman-Diamond syndrome (SDS) is usually caused by mutations in the SBDS gene, but some patients have mutations in another gene called DNAJC21. Because SDS is so rare, and mutations in DNAJC21 are even more rare, researchers often use animals, known as model organisms, like fish, mice, fruit flies, or other animals to study it. Using model organisms to study SDS and other rare diseases helps scientists better understand the disease and develop potential treatments. This is why SDS Alliance, in collaboration with the Jackson Laboratory, is committed to generating a mouse model with mutations in the SBDS gene that scientists can use to understand SDS and ask important questions that will advance treatment development for SDS.

In the SDS & Science Snapshot this week, we are highlighting a new study published by scientists at the CHEO Research Institute (Ottowa, Canada) and colleagues which used zebrafish, a different model organism than mice, to investigate the impact of germline mutations in DNAJC21 on the development of SDS-related symptoms and identify potential treatment opportunities.

Why Zebrafish Are Important for SDS Research

Zebrafish are tiny fish that are often used in research because they share many genetic similarities with humans. Their fast growth and transparent embryos make them ideal for studying how genes work, particularly in conditions which affect the blood and bone marrow (like SDS). The use of zebrafish as a model organism for SDS and SDS-associated conditions is not new – zebrafish have been used as a model organism for SDS in previous research studies as well (here is a link to one example).

In this study, scientists used zebrafish to model SDS caused by mutations in the DNAJC21 gene. By creating zebrafish with similar mutations, researchers can observe the effects of these mutations in a living organism, which provides valuable insights into how the disease affects humans. For more information about the importance of zebrafish and other model organisms in research, you can watch the video below.

Key Findings and Potential New Treatment Opportunities

The researchers found that zebrafish with mutations in the dnajc21 gene (the zebrafish equivalent of DNAJC21) showed symptoms similar to those seen in SDS patients. These fish had lower numbers of certain types of blood cells, grew more slowly, and had other health problems. This shows that the dnajc21 gene in zebrafish is important for normal blood cell production and overall growth, just like the DNAJC21 gene in humans.

One of the exciting findings from this study is that the researchers identified a new role for the zebrafish dnajc21 gene in controlling the production of nucleotides, which are the building blocks of DNA and RNA. When nucleotide levels were low (as a result of mutations in the dnajc21 zebrafish gene), the zebrafish developed problems with blood cell production. However, when the researchers gave the fish extra nucleotides, their blood cell counts improved. This suggests that treatments aimed at increasing nucleotide levels might help manage SDS symptoms in humans.

The Role of p53 and its Impact on SDS

The study also explored the role of another gene shared between zebrafish and humans, TP53, which is known to be involved in cancer and cell death. When the researchers introduced a somatic tp53 mutation into the dnajc21-mutant zebrafish, they observed some improvement in blood cell counts. However, this also led to other problems, like the development of myelodysplastic syndrome (MDS), a condition where blood cells don’t mature properly and can lead to leukemia. This finding highlights the complex relationship between different genes in SDS and how they can influence the disease’s progression. For more information, you can review this previous SDS & Science Snapshot which discusses another study investigating the role of acquired (or somatic) TP53 mutations in individuals with SDS.

What This Research Means for SDS Patients and Families

Although this research is still in the early stages, it provides a valuable foundation for future research studies and potential new treatments development. Research using zebrafish and other model organisms help scientists understand SDS better and offers hope for new treatments. By uncovering how different genes contribute to SDS and SDS-associated conditions, researchers can develop more targeted therapies. For patients and families living with SDS, these findings are a step forward in finding ways to navigate life with SDS and improve treatments.

Ketharnathan S, Pokharel S, Prykhozhij SV, Cordeiro-Santanach A, Ban K, Dogan S, Hoang HD, Liebman MF, Leung E, Alain T, Alecu I, Bennett SAL, Čuperlović-Culf M, Dror Y, Berman JN. Loss of Dnajc21 leads to cytopenia and altered nucleotide metabolism in zebrafish. Leukemia. 2024 Aug 13. Epub ahead of print. PMID: 39138265.

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Welcome to our timely updates on all things SDS, Science, and Advocacy. We bring you a digest of recent scientific publications, conferences, and other newsworthy content - all relevant to SDS - with links to more details and learning opportunities. Are you interested in anything specific? Did we miss something? Let us know. Email genetics@SDSAlliance.org or message us on Facebook! This is all for you!

New Publication by the SDS Alliance: From Challenge to Opportunity: How Shwachman-Diamond Syndrome Became a Promising Target for Therapy Development

The efforts of the SDS Alliance are bringing new hope to the SDS community. SDS Alliance’s very own President and CEO, Eszter Hars, Ph.D. and Dr. Lisa McReynolds, Assistant Clinical Investigator at the National Cancer Institute and member of the SDS Alliance Medical and Scientific Advisory Board published an article in the peer-reviewed Journal of Clinical Pharmacology and Therapeutics. In this article, they described how the efforts of SDS Alliance and other investigators in the SDS community have positioned SDS as a promising target for new therapies.

Eszter shares: "The three major goals of this publication are to: ● Alert physicians about the new ICD-10 code for SDS ● Attract industry interest to the SDS field for therapy development ● Share our work with the SDS community and demonstrate how we, the patient community, can shape the future for our loved-ones by a driving and accelerating research"

This figure from the article summarizes why SDS is a model rare disease and ready for therapy development. De-risking means removing barriers in research, in order to give therapy developers confidence that their investment is worth while and that therapy development will be financially viable for SDS.

Below, we’ll explore how publishing these perspectives and advancements in a peer-reviewed journal pave the way for more research, better care, and the potential for life-changing treatments for the SDS community.

The Importance of Publishing in a Scientific Peer-Reviewed Journal

Publishing in these high quality journals allows high quality work to reach doctors and researchers who can use this information to further advance research. Researchers of a wide range of life-science disciplines rely on special search engines to keep up to date on the latest research and scientific insights. Instead of Google, they use PubMed, which is focused on scientific journals and other publications and organizes the basic information about the articles in a way that allows users to find relevant articles quickly, easily, reliably, and FREE. Learn more about PubMed below, and explore additional videos to dive deeper. Or just try it yourself!

By publishing this article in a high-quality scientific journal - indexed by PubMed - the SDS Alliance is now able to reach doctors and researchers who are not yet engaged in the SDS community, in addition to existing experts. Here is the link to our article on PubMed. PubMed users can set up alerts based on their research interest and keywords, to receive emails if a new article is published that match those search criteria. For example, Shwachman-Diamond Syndrome, or inherited bone marrow failure, or congenital neutropenia. Now all doctors/researchers who use alerts or who search PubMed regularly will have received an alert about our publication, and have the opportunity to learn about a new angle to see the SDS patient community and our work.

Below, you can see how our article appears on PubMed. We circled the button that leads to the full text of our article on the journal publisher's website (Wiley). There, you can read the full article - both the web version (easier to read on a screen) and a PDF version that looks like the printed version that will be distributed to libraries and subscribers later this year.

When research is published in a peer-reviewed journal, it means that other experts in the field have reviewed and validated the work. This process ensures that the information is accurate, reliable, and valuable to the scientific community. For the SDS community (and many other rare disease communities), being published in such journals is important because it increases credibility and visibility. It helps attract attention from researchers, companies, and healthcare providers who might not be aware of SDS. This recognition can lead to more research, funding, and eventually, new treatments that could make a big difference in the lives of SDS patients and their families.

Understanding ICD-10 Codes and Their Importance in Rare Disease

ICD-10 codes are special codes used by doctors and hospitals to identify and track diseases. For rare diseases like Shwachman–Diamond Syndrome (SDS), having a unique ICD-10 code is a big deal. It helps doctors and researchers track the condition and learn more about how it affects the SDS patient community over time, what treatments work better than others, what complications to watch for, and other invaluable data. This data can be used to understand the disease better and to develop new treatments. In 2023, SDS received its own ICD-10 code, D61.02, which marks a significant step forward for the SDS community. This new code makes SDS more visible in the medical world, leading to better care for patients and more research opportunities. If you haven’t already, we encourage you to share the ICD-10 code for SDS, D61.02, with your care team! 

Why The Work of SDS Alliance Matters for Developing New Treatments

This article highlights why it's crucial to bring SDS to the attention of biopharmaceutical companies—those who develop new medicines. SDS is an exceptionally good candidate for therapy development because its genetic causes are well understood, and there is strong support from the patient community and researchers. At SDS Alliance, we are dedicated to supporting SDS research and patients, and continue to work hard to establish and foster relationships with companies who support the goals and mission of SDS Alliance, including therapy development.

With the new ICD-10 code, there’s now a new path for gathering data and understanding the disease better, which can aid in the development of effective treatments. This makes it more likely that companies will see the potential in developing therapies for SDS, which could change the lives of those affected by this rare condition.

The Promise of SDS Alliance to Support the SDS Community

With this publication, SDS Alliance highlights and summarizes our work dedicated to the SDS community to improve the lives of those with SDS and to positively contribute to the development of new therapies. Securing the ICD-10 code for SDS is one of the impactful contributions toward making SDS visible and accessing relevant data for therapy development strategies.

By supporting research, providing important tools and data, and fostering a strong patient community, SDS Alliance is not only helping to bring attention to SDS but also paving the way for new and better therapies. Together, our work ensures that SDS patients are heard and that our needs are at the center of therapy development in the future.

Hars ES, McReynolds LJ. From Challenge to Opportunity: How Shwachman-Diamond Syndrome Became a Promising Target for Therapy Development. Clin Pharmacol Ther. 2024 Jul 22. Epub ahead of print. PMID: 39039619.

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Welcome to our timely updates on all things SDS, Science, and Advocacy. We bring you a digest of recent scientific publications, conferences, and other newsworthy content - all relevant to SDS - with links to more details and learning opportunities. Are you interested in anything specific? Did we miss something? Let us know. Email genetics@SDSAlliance.org or message us on Facebook! This is all for you!

Understanding the Role of Blood and Bone Marrow Stem Cell Mutations and Their Impact on SDS Progression and Treatment

Shwachman-Diamond Syndrome (SDS) is a rare genetic disorder that affects the bone marrow, pancreas, and skeletal system. Recently, researchers have made significant strides in understanding how somatic (or acquired) genetic mutations play a role in the bone marrow failure of patients with SDS. Dr. Alan Warren and his team recently published a review of these advancements in Blood, the official journal of the American Society of Hematology. 

One study highlighted in this review used advanced techniques to map relationships between the blood and bone marrow stem cells in patients with SDS, shedding light on the mutations that may influence the development and progression of MDS and AML. This was done by analyzing individual stem cells from the blood and bone marrow of ten SDS patients aged 4 to 33 years. Researchers discovered that most of these patients had large groups of bone marrow stem cells with a lot of somatic (or acquired) genetic mutations, such as mutations in the TP53 gene, a pattern usually seen in much older individuals. This suggests that blood and bone marrow stem cells in SDS patients are affected early in life, contributing to the development of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) at younger ages. 

Another recent finding highlighted by this review, was the role of acquired (somatic) mutations and how the different somatic mutations interact. While acquired (somatic) mutations were common in the blood and bone marrow stem cells of patients with SDS, not all somatic mutations led to severe consequences. Interestingly, some somatic mutations seemed to help cells survive better despite the SDS-related defects. These "rescue" mutations potentially lower the risk of disease progression to MDS or AML. However, when acquired TP53 mutations occur in both copies of the gene, it can lead to severe conditions like MDS or AML. For more information regarding the development of clones and the difference between somatic and germline variants, watch the video below or review these previously published SDS & Science Snapshots (Somatic and Germline Variants or The Difference between Germline and Somatic Genetic Testing).

The review published by Dr. Warren and his team shared that multiple recent studies have had similar findings, reporting that up to 72% of SDS patients often develop clonal hematopoiesis (CH). CH happens when some blood and bone marrow stem cells with specific “signatures” of acquired (or somatic) mutations start to dominate, but other features of MDS and AML are not present in the bone marrow. The acquired CH mutations observed in SDS patients were usually different from those seen in older adults without SDS. By tracking these mutations over time, researchers hope to better understand how they affect disease progression from CH to MDS and AML. For more information about clones, how they develop, and how to monitor the development of them, watch the video below.

Dr. Warren and his team emphasized the timing of when these somatic mutations occur is also crucial. By building a "family tree" of stem cell mutations, researchers can estimate when specific mutations happened. Some mutations in SDS patients can occur very early, even before birth. Following the “family tree” of somatic mutations and how they relate to early somatic mutations highlights the importance of monitoring SDS patients from a young age.

Dr. Warren presented part of this work and background virtually as part of the 2024 Expert Webinar Series, hosted by our Australian partner organization, Maddie Riewoldt's Vision, focused on funding research to discover cures for Bone Marrow Failure Syndromes.

For families and patients with SDS, these findings emphasize the importance of regular bone marrow biopsies and somatic genomic testing (also known as NGS) on these bone marrow biopsy samples and/or on peripheral blood samples. Understanding which somatic mutations are present in the blood and bone marrow of SDS patients can help doctors predict the risk of disease progression and make informed decisions about treatments, including the potential of bone marrow transplant. As research advances, it may also lead to new therapies that target specific somatic mutations or pathways, offering hope for better outcomes in the future.

Cull AH, Kent DG, Warren AJ. Emerging genetic technologies informing personalized medicine in SDS and other inherited bone marrow failure disorders. Blood. 2024 Jun 21:blood.2023019986. Epub ahead of print. PMID: 38905596.

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Welcome to our timely updates on all things SDS, Science, and Advocacy. We bring you a digest of recent scientific publications, conferences, and other newsworthy content - all relevant to SDS - with links to more details and learning opportunities. Are you interested in anything specific? Did we miss something? Let us know. Email genetics@SDSAlliance.org or message us on Facebook! This is all for you!

Unlocking the Secrets of Early Development in SDS with Induced Pluripotent Stem Cells

Shwachman-Diamond syndrome (SDS) is a rare genetic disorder that affects the bone marrow, leading to a shortage of blood cells. It can also cause other problems in the body and increase the risk of leukemia, a type of cancer. The disorder is mainly caused by mutations in the SBDS gene, which is important for making ribosomes, the cell’s protein factories. Without proper SBDS function, not enough ribosomes can form, leading to many of the issues seen in SDS.

In the SDS & Science Snapshot this week, we are highlighting a recent study led and published by Dr. Yigal Dror, a leading physician-researcher on inherited bone marrow failure syndromes from The Hospital for Sick Children (SickKids in Toronto). In this study, Dr. Dror and his research team wanted to find out exactly when the blood cell problems of individuals with SDS begin during development with the hopes of guiding future research in therapy development.

To do this, Dr. Dror and his research team created a special type of cell called induced pluripotent stem cells (iPSCs) using cells from bone marrow samples from SDS patients and healthy controls, which can turn into any cell type in the body. This ability to “shape shift” makes iPSCs a powerful tool for studying early embryonic development, as they can be used to observe how diseases or genetic conditions affect the formation of different cell types from the very beginning. Additionally, iPSCs can be used to model diseases in the lab, allowing scientists to explore new treatments and understand the underlying mechanisms of various disorders without the need for embryonic stem cells. For more information about the important use of iPSCs in research, you can watch the video below.

Key Findings from this Study:

1. Lower Efficiency in Cell Reprogramming: The researchers found that it was much harder to create iPSCs from SDS patients compared to heathy donors, suggesting that cells from SDS patients are either less fit or have a reduced ability to be reprogrammed into stem cells.

2. Defects in Blood Cell Formation: When the iPSCs from SDS patients were encouraged to become blood cells, they formed far fewer blood cells than the healthy iPSCs. This means that the blood cells in SDS patients have trouble developing properly, which can explain the issues with healthy blood cell development (like neutropenia) seen in SDS patients.

3. Early Developmental Issues: The study also showed that the problems start at a specific stage of blood cell development, known as the early emerging hematopoietic progenitors (EHPs) stage. This is an early step in the process where stem cells start to become specialized blood cells. SDS cells had fewer EHPs, and these cells were less able to grow and multiply.

4. Potential for New Treatments: One exciting aspect of this study is that the researchers found that adding back the SBDS gene to the SDS iPSCs improved their ability to form blood cells. This suggests that gene therapy, which aims to correct the defective gene, might be a promising treatment for SDS. Additionally, understanding the specific stages and processes affected by SDS helps in designing drugs that can target these problems more precisely, and provides a rationale to apply treatments as early in life as possible.

5. Mapping Gene Pathways in SDS: Lastly, the researchers in this study investigated the gene expression during early development of these iPSCs from SDS patients. By analyzing these iPSCs, they identified important genes and cellular pathways that are activated or repressed at various stages of cell development. This detailed mapping of gene activity may help in understanding the differences between healthy and SDS iPSCs, providing valuable information for developing targeted therapies for SDS.

Understanding exactly when and how blood cell problems start in those with SDS can help scientists develop better, more effective treatments. By knowing that the defect begins at the EHP stage, researchers can target this stage to find ways to prevent or correct these defects. These findings could help lay the groundwork for new therapies that can improve blood cell production in SDS patients, reducing the need for frequent treatments and improving quality of life. This also underscores the critical importance of early and accurate diagnosis of SDS, so that any treatment can be started as early in life as possible, when the benefits may be the biggest. With continued research, there is potential for significant improvements in managing and treating SDS!

Lagos-Monzon A, Ng S, Luca AM, Li H, Sabanayagam M, Benicio M, Moshiri H, Armstrong R, Tailor C, Kennedy M, Grunebaum E, Keller G, Dror Y.

Aberrant early hematopoietic progenitor formation marks the onset of hematopoietic defects in Shwachman-Diamond syndrome. Eur J Haematol. 2024 Jul 5. PMID: 38967591.

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Welcome to our timely updates on all things SDS, Science, and Advocacy. We bring you a digest of recent scientific publications, conferences, and other newsworthy content - all relevant to SDS - with links to more details and learning opportunities. Are you interested in anything specific? Did we miss something? Let us know. Email genetics@SDSAlliance.org or message us on Facebook! This is all for you!

SDS Alliance Announces Collaboration with Rare Genomes Project

Timely and accurate diagnosis of Shwachman-Diamond Syndrome (SDS) is critical for patients to access optimal care, education, and community support. We are excited to announce our new collaboration with the Rare Genomes Project (RGP) at the Broad Institute of MIT and Harvard. The RGP is a free and remote research program using genomic sequencing to look for the genetic cause of rare diseases, such as SDS. Eligible families will be asked to provide a blood sample and medical information. If a result is found, the RGP team will work with your doctor to confirm the result.

What is the purpose of this study?

The Rare Genomes Project is a research study focused on patients and families with rare and genetically undiagnosed conditions, now including those suspected to have SDS. The RGP uses genomic sequencing to search for the cause of rare disease in these families and hopes to accelerate the rate of rare disease diagnosis in the process. 

How is the genetic sequencing done?

What is particularly exciting about this project is that it uses Whole Genome Sequencing (WGS), sequencing the entire genome, not "just" the coding sequences called as genes (as in Whole Exome Sequencing (WES)) but also everything in between. Are you curious how WGS is done? Check out this short video overview, below. For more details about the difference between WGS and WES, check out this video.

Who is eligible to participate in our new collaboration?

• Those who have a clinical suspicion for SDS, including a history of two or more of the symptoms listed below. (“A history of'' means that these symptoms may have happened in the past and resolved by the time participation in the RGP is considered.)

Exocrine pancreatic insufficiency (EPI): Decreased pancreatic enzymes (serum trypsinogen or pancreatic isoamylase), decreased fecal elastase, malabsorption, or steatorrhea

Hematologic abnormalities: Cytopenias including neutropenia, hypocellular bone marrow, bone marrow failure, or MDS/AML

Skeletal dysplasia: Rib cage/thoracic abnormality, metaphyseal dysostosis, extremity abnormalities, scoliosis, or abnormal bone density

• Individuals with a suspected genetic cause that has not been identified due to prior testing being negative or inconclusive OR a lack of access to genetic testing. (This means that patients who have received genetic testing previously ARE eligible to participate, as long as prior testing has not yielded a diagnosis.)

• Applicants for the RGP must live in the United States.

How do I get involved?

Participation is initiated by eligible patients and families by completing an online application which asks questions about personal and family medical history. The RGP research team will review your application to determine eligibility - this application review process may include a request for additional medical records. Eligible families will also be invited to participate in a virtual introductory meeting to meet the RGP team and discuss participation details such as submitting a blood sample. For more information, you can watch the video below or visit this webpage on the RGP website.

Will I receive genetic testing results?

The goal of the RGP-SDSA collaboration is to find the genetic explanation for SDS in each family who enrolls, but the RGP cannot guarantee that they will have a result for each family. Because this is research-based genetic testing, the process is expected to take longer than routine genetic testing. If the RGP finds a genetic variant(s) that may explain SDS in the family member with the condition, the RGP team will work with affected individuals to clinically confirm and return the results. The RGP does not return results to unaffected family members.

How will I receive genetic testing results?

If the RGP finds results that they believe explains the underlying cause of SDS present in your family, they will contact you and ask if you would like to have the findings clinically confirmed in a CLIA-certified laboratory. A genetic counselor on the RGP staff will work with a doctor of your choice to order testing through the CLIA-certified lab. The doctor who orders the clinical test will be the one who shares the results with you.

If this project sounds like it could benefit you or a loved one, we encourage you to fill out an application on the RGP website.

More resources

• The SDS Alliance team is available for guidance at connect@SDSAlliance.org. 

• At SDS Alliance, we have assembled resources for possible patients and their healthcare providers to access no-cost testing options, wherever you are.

• This page is dedicated to the SDSA partnership with the Rare Genomes Project to provide access to whole-genome sequencing on a research basis to US residents.

• If this program doesn't work for you, please check out our other resources or email us at connect@SDSAlliance.org. 

• Download a printable flyer here, available in English and Spanish:

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At the beginning of 2023 we found out with great joy that we will be expecting our second child and we could not be happier knowing that our family will grow.

The pregnancy was monitored carefully each trimester and for the first two, it seemed to be all ok, the baby was growing as expected, everything was within normal parameters. That was until one of our check-ups during the 3rd trimester, where after an ultrasound examination, the doctors informed us that it seems that the baby's limbs are not growing in accordance with his gestational age and the doctors were starting to suspect a possible genetic condition (achondroplasia).

Of course, we were devastated to even consider that our yet unborn baby boy could be in any way sick, and went through all the possible stages - crying, denial, anger, - you name it... Regardless, there was nothing we could do but wait and see...

Finally, October arrived and Octavian was born at the maternity hospital in our city in Romania. His APGAR score was 9, as for the first hours outside the womb, he had some breathing related issues, but thank God, afterwards his breathing got better and did not need to undergo any more oxygen therapy. He was quite small, 46 cm and 2.6 kg but was from the start, very very beautiful.

The genetics department from the maternity hospital suggested we should test him for achondroplasia, but as my parents are pediatricians, they both suggested that it makes no sense, because from their experience it was clearly not the case of achondroplasia. They were the ones that encouraged us to go for the Whole Exome Testing and did so in November.

For the first 3 months, Octavian was doing quite well, he was eating well (breastfed + extra formula) and was gaining steadily weight at a normal rate. We were very proud of our little man because even when he had the misfortune of contracting pneumonia from his older brother, he still did not lose weight, and was still eating with pleasure.

Close to Christmas time, he started eating smaller and smaller portions, and showing signs of abdominal distress, so we tried to switch to any possible formula for the coming period and giving him any possible supplements to help with digestion. Now we entered the stage where he simply stopped gaining weight and was somehow blocked at 3.9 kg for almost 2 months...

In the meantime, we got the results back from the Whole Exome Genetic Testing and we celebrated because it clearly stated he has NO achondroplasia. For about 2-3 days we just couldn’t realize that there was something else highlighted in the results:

• The patient is heterozygous for EFL1 [...], which is a variant of uncertain significance (VUS).

• The patient is heterozygous for EFL1 [...], which is a variant of uncertain significance (VUS).

Biallelic pathogenic variants in EFL1 have been associated with Shwachman-Diamond syndrome 2 (SDS; MIM #617941; GeneReviews NBK1756), an autosomal recessive disorder characterized by exocrine pancreatic insufficiency, bone marrow dysfunction, skeletal abnormalities, and short stature.

At some point, again my parents suggested to test his elastase levels from his stool and we got back two consecutive results for exocrine pancreatic insufficiency….Now it started to become clear to us that it could be the case that our son has SDS….It came as a shock to us to find out that at our centers for Cystic Fibrosis, the doctors have never seen SDS…We felt pretty much on our own, until one day we went online and found the SDS support group and got in touch with multiple people and patients and were all of the sudden surrounded by information and encouragement from the group.

Eszter Hars of the SDS Alliance was one of the people that helped us the most from the community, she helped us get in contact with specialist in Europe that have experience with SDS and in April we were lucky to be accepted for a visit at Dr. Cipolli Marco in Verona Italy. We were happy to be in the hands of specialists that know how to handle Octavian’s condition.

A holistic approach of his condition was undertaken in Verona and after careful evaluation, Octavian was confirmed clinically with SDS. 

[Editorial comment: due to the mutations being classified as VUS, the patient received his diagnosis by an SDS expert based on clinical (symptom) findings, which is known as a clinical diagnosis as opposed to genetic confirmation. About 10% of SDS patients are diagnosed clinically].

This condition was classified as being mild, showing skeletal abnormalities in the form of a narrow chest and pancreatic insufficiency. His bloodwork is ok, showing no signs of neutropenia or anemia.

We came back to Romania with a plan and clear indications on how to administer enzymes to help him digest food and we have scheduled a follow up visit in the coming year.

Octavian is now 8 months old. He is still small for his age and is still struggling to reach the milestones that most kids reach by the age of 8 months because of his hypotonia. He is now 60cm tall and weighing 4.6 kg.

Despite his condition he is a very happy little man. He smiles all the time, he is very happy to spend time with his older brother and is musically inclined – his face lights up when we put music on. 

We have come a long way in just 8 months, 8 months ago we never heard of SDS and never even considered the chance of our child to suffer from a rare disease… We learned in this short period that we are strong together, and that there is a community that we can rely on when in need.

We went from being completely lost, to having a plan, and for the first time in our SDS journey I think we have reached as a family the stage of acceptance and trying to live life the fullest despite SDS.

[Written and submitted from Octavian's dad, Raul]

Welcome to our timely updates on all things SDS, Science, and Advocacy. We bring you a digest of recent scientific publications, conferences, and other newsworthy content - all relevant to SDS - with links to more details and learning opportunities. Are you interested in anything specific? Did we miss something? Let us know. Email genetics@SDSAlliance.org or message us on Facebook! This is all for you!

New Insights into Lung Microbiomes and Bone Marrow Transplant Outcomes

When children undergo bone marrow transplant (BMT), such as those with Shwachman-Diamond Syndrome (SDS), even small infections, such as respiratory infections, can become very dangerous. A team of scientists around the world recently published a new method to quickly identify all the microscopic organisms in the lungs of these children after BMT with the hopes of improving transplant outcomes. 

This collection of microscopic organisms, referred to as the microbiome, includes bacteria, viruses, fungi, and other microbes, that live all over our bodies, including inside the lungs. Just like the gut microbiome, the lung microbiome plays a crucial role in maintaining health and protecting against infections. A balanced lung microbiome helps the immune system function properly, whereas an imbalance can make individuals more susceptible to diseases and infections. The researchers of this study discovered that certain groups of microbes in the lungs can predict which patients after BMT are at higher risk of dying from lung infections.

The video below explores the origin, purpose, and importance of the human microbiome.

Researchers in this new study used a technique called metagenomic next-generation sequencing (mNGS) to examine the microbiome of lung fluid from many pediatric patients after BMT. This method allowed the researchers to find and categorize all the microbes in the samples. Importantly, these researchers identified four different groups of patients based on the types and amounts of microbes in their lungs, helping them predict which children were more likely to suffer severe lung injuries, including lung infections.

Bone marrow transplants can be life-saving interventions for children with leukemia, bone marrow failure, and genetic disorders like SDS. However, the process of BMT involves strong chemotherapy that weakens the immune system and makes these individuals highly susceptible to infections. Unfortunately, these infections can be deadly, especially when patients need ventilators. Traditional tests may miss some pathogens (like bacteria and viruses) that cause these infections after BMT, but mNGS can identify a wide range of microscopic organisms, including rare ones, enabling more accurate treatments and improve outcomes.

By analyzing the mNGS data of these microscopic organisms in the lung microbiome of bone marrow transplant patients, the researchers discovered that patients in the group with the highest risk of death after bone marrow transplant not only had fewer types of microbes in their microbiome, but also had more Staphylococcus bacteria and viruses. This research suggests that a balanced lung microbiome is crucial for better bone marrow transplant outcomes.

For children with Shwachman-Diamond Syndrome (SDS), who are prone to infections and often need bone marrow transplants, these findings are especially important. Understanding the lung microbiome could help doctors better predict and treat infections in these patients. Using mNGS could lead to more precise treatments, improving survival rates for SDS patients undergoing transplants by allowing doctors to quickly identify and address the specific microbes causing infections after bone marrow transplant.

The SDS & Science Snapshot this week contains content modified from materials in this blog post, Lung Microbiomes Predict Mortality in Children Following Bone Marrow Transplant, published the Chan Zuckerburg Biohub Network.

Zinter MS, Dvorak CC, Mayday MY, Reyes G, Simon MR, Pearce EM, Kim H, Shaw PJ, Rowan CM, Auletta JJ, Martin PL, Godder K, Duncan CN, Lalefar NR, Kreml EM, Hume JR, Abdel-Azim H, Hurley C, Cuvelier GDE, Keating AK, Qayed M, Killinger JS, Fitzgerald JC, Hanna R, Mahadeo KM, Quigg TC, Satwani P, Castillo P, Gertz SJ, Moore TB, Hanisch B, Abdel-Mageed A, Phelan R, Davis DB, Hudspeth MP, Yanik GA, Pulsipher MA, Sulaiman I, Segal LN, Versluys BA, Lindemans CA, Boelens JJ, DeRisi JL.

Pediatric Transplantation and Cell Therapy Consortium. Pathobiological signatures of dysbiotic lung injury in pediatric patients undergoing stem cell transplantation. Nat Med. 2024 May 23. PMID: 38783139.  

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Welcome to our timely updates on all things SDS, Science, and Advocacy. We bring you a digest of recent scientific publications, conferences, and other newsworthy content - all relevant to SDS - with links to more details and learning opportunities. Are you interested in anything specific? Did we miss something? Let us know. Email genetics@SDSAlliance.org or message us on Facebook! This is all for you!

Ask an Expert Recap: The Difference between Germline and Somatic Genetic Testing

At the most recent Ask an Expert webinar in May (see below), we heard from Dr. Lisa J. McReynolds, one of the newest members of the SDS Alliance Medical and Scientific Advisory Board (you can read her biography and more about her work here and welcome to the SDS Alliance community, Dr. McReynolds!). In this meeting, one of the topics discussed was the importance of diagnostic genetic testing for individuals with SDS and how hereditary (germline) variants (or mutations) are different from somatic mutations detected in cancerous (or pre-cancerous) cells, also known as clones. In our SDS & Science Snapshot this week, we will discuss the difference between these two mutation types (and how they are tested for) in more detail.

In the world of cancer, there are two main types of genetic tests that are used to inform care: germline genetic testing and somatic tumor (genomic) testing. Understanding the difference between these two types of mutations can be helpful in navigating the complexities of SDS. In a previous SDS & Science Snapshot, we discussed the difference between germline and somatic variants (or mutations). 

The figure below compares germline genetic testing and somatic genomic tumor testing. Sometimes in the clinic, somatic genomic tumor testing is also referred to as “NGS” (which stands for “next-generation sequencing”) and is frequently performed on the bone marrow biopsy samples from patients with SDS as discussed below.

While the results of these two types of genetic testing often look similar, there are a few key differences in the somatic genomic tumor testing to look out for:

• Variant allele frequency (VAF): This is how often the variant (or variants) were seen in the tested sample of cancerous (or pre-cancerous) cells. VAF provides insights to how predominant the variant (or variants) may be in the tumor sample. Knowing the VAF of somatic variants detected in a bone marrow biopsy sample can help your care team monitor for the development of MDS or AML or give insight into how someone with MDS or AML is responding to treatment.

  • Key difference: Sometimes germline variants can be identified on somatic genomic testing, but the VAF of germline genetic variants is typically around 50% and, if detected, are generally expected to remain constant across multiple somatic genomic tests. This is in comparison to the VAFs of somatic mutations, which change over time as the clones of cancerous cells develop and evolve over time. 

• Genes: Some genes are more commonly altered in pre-cancerous or cancerous cells than others. For example, TP53 variants are frequently seen in the bone marrow samples of individuals with MDS or AML, but most of those individuals do not have a germline TP53 variant, or Li Fraumeni Syndrome. Other examples of genes commonly mutated in the bone marrow samples of individuals with MDS or AML include DNMT3A, TET2, CSF3R, SF3B1, IDH1/2, RUNX1, and GATA2.

• Report Comments: Somatic genomic tumor testing (or NGS) are not meant to detect germline variants. If there is concern for the accidental detection of a germline variant that may play a role in a patient’s care plan, there will often be a comment about this in the NGS report. 

For more information regarding the development of clones and the difference between somatic and germline variants, you can watch this educational video on the genetics of SDS. We cover the concept of germline versus somatic variants (around minute 5), and how they relate to leukemia. You might also find it helpful to watch the recording of the Ask an Expert webinar with Dr. Lisa J. McReynolds above.

We encourage you to ask your healthcare provider about any questions you have about any genetic testing results, germline or somatic, and how these are used to manage care.

For more information regarding the difference between somatic and germline variants, you can visit the Cleveland Clinic’s website.

The SDS & Science Snapshot this week contains content modified from materials in this blog post, Tumor Genetics: Somatic vs Hereditary, published by Quest Diagnostics.

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