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 Study Publishes Custom Growth Charts for Individuals with SDS from Childhood to Adulthood

You've probably seen growth charts at the doctor's office or in a medical record — they track how kids grow over time, comparing their height and weight to others their age. But for some, like those with Shwachman-Diamond Syndrome (SDS), those charts might not tell the whole story.

As we know, SDS is a complex disorder affecting many systems. The majority of individuals with SDS have some degree of exocrine pancreatic insufficiency. This can lead to problems with digesting food and getting the right nutrients, which can cause them not to grow as much as other kids. Other common symptoms of SDS include failure to thrive and skeletal abnormalities, which also impact an individual’s growth and development compared to someone without SDS. So, using regular growth charts can be misleading for someone with SDS because their growth might not match what's expected for their age group.

That's why custom (or disease/population specific) growth charts are so important for people with SDS. These growth charts are made just for them, considering their unique needs and challenges. Unlike regular growth charts, which might suggest they're not growing well, personalized growth charts give a clearer picture of how they're doing. Until recently, custom growth charts were only available to individuals with SDS from 0 to 8 years of age. earlier this month, researchers in Italy published custom growth charts created for individuals with SDS from 0 to 18 years of age! These growth charts (pictured below) for height (a-b), weight (c-d), and BMI (e-f) were created from a large cohort of 121 individuals with SDS and over 700 growth measurements for both males (left panel) and females (right panel).

Growth charts for males (left) and females (right) with SDS for height (a-b), weight (c-d),

and body mass index (BMI; e-f) of patients with SDS from ages 0 to 18 years.

These researchers found that the 50th and 3rd percentiles of weight and height of the pediatric general population corresponds to the 97th and 50th percentiles of patients with SDS aged 0-18 years, respectively. In other words, if a child with SDS weighs in at about the 3rd percentile on the generic growth chart, that would correspond to the 50th percentile on the SDS growth chart. This could then be interpreted as the child doing well, right on target/average in terms of their weight compared to other children who also have SDS. Of course, families are encouraged to discuss such interpretations and all treatments with their health care team. This finding is an example of how using regular growth charts can be misleading for someone with SDS because their growth might not match what's expected for their age group.

Personalized growth charts for SDS not only help you to understand how individuals with SDS are growing, but it can also help doctors track how well treatments are working. For example, if someone with SDS tries a new medicine or therapy, this growth chart for individuals with SDS can show if it's helping them grow stronger and healthier.

These growth charts also help families understand their child's growth better, from 0 to 18 years. Instead of feeling confused by the numbers, you can see how your loved one is doing compared to others with SDS. This can help you feel more confident in managing your loved one’s health and making decisions about their care.

We encourage you to share this publication and these growth charts with your healthcare team to see how they can help you in your journey with SDS!

Pegoraro A, Bezzerri V, Tridello G, Brignole C, Lucca F, Pintani E, Danesino C, Cesaro S, Fioredda F, Cipolli M. Growth Charts for Shwachman-Diamond Syndrome at Ages 0 to 18 Years. Cancers (Basel). 2024 Apr 5;16(7):1420. doi: 10.3390/cancers16071420. PMID: 38611098.

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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!

What is EuNet-INNOCHRON?

EuNet-INNOCHRON is an ACTION OF EUROPEAN COOPERATION IN SCIENCE AND TECHNOLOGY, and is an abbreviation for European Network for Innovative Diagnosis and Treatment of Chronic Neutropenias.

Chronic neutropenias (CNP) represent a wide spectrum of disorders ranging from mild to life-threatening, acquired or congenital diseases. Shwachman-Diamond Syndrome is part of this category, specifically part of the congenital neutropenia subtype.

The pathophysiological mechanisms underlying CNPs are diverse and vary from haemopoietic stem cell and bone marrow microenvironment defects resulting in impaired neutrophil production, to immune disturbances leading to accelerated apoptosis of neutrophil progenitors and/or the circulating mature neutrophils. The prognosis of patients with CNP is related to the underlying pathogenesis, the degree of neutropenia and the propensity for leukaemic transformation.

Accurate diagnosis is mandatory for risk stratification and treatment choice.

The principal challenge of the Action is to establish a wide network of researchers with special interest in CNPs and facilitate interactions and collaborations among top-level European experts and young investigators from different scientific areas i.e. Clinical and Laboratory Haematology, Immunology, Genetics, Molecular Biology and Regenerative Medicine.

The main aims of the Action are:

1. to promote science, training and education on advanced biochemical, immunological, genetic and molecular biology techniques for the accurate diagnosis and treatment of patients with different types of CNP, early recognition of Myelodysplastic Syndromes/Acute Myeloid Lekaemia evolution and appropriate intervention,

2. to link and further expand existing neutropenia networks for a more multidisciplinary approach of CNP that will result in a better characterization of the underlying diseases and development of individualized and precision medicine therapeutic approaches for selected patients,

3. to organize and expand CNP patient Registries and Biobanks using homogenized protocols in line with the ethical standards of the European Legal Framework and the relevant national regulations.

How did the SDS Alliance highlight the patient voice?

The SDS Alliance was invited to present the patient perspective and our advocacy efforts, and the organizers were very accommodating by providing virtual access to this impactful in-person meeting. Dr. Hars focused her talk on two areas. First, she shared patient stories and the impact SDS has on patients and their families. Second, she highlighted the SDS Alliance's programs to accelerate research toward therapies and cures. These focus areas and their progress are also highlighted on our website on our Strategy & Roadmap page.

What was the Final Conference and Working group meeting about?

The Final Conference of EuNET-INNOCHRON (European Network for the Innovative Diagnosis and Treatment of Chronic Neutropenias) Research Newtork - a COST Action - focusing on research in the field of chronic neutropenias, took place April 4-6, 2024 at the KAM Center of Mediterranean Architecture in Chania, with limited virtual access to selected speakers.

The chair of the COST Action CA18233 EuNet-INNOCHRON, Helen Papadaki, Professor of

Hematology School of Medicine, University of Crete and Director of the Hematology Department of the University Hospital of Heraklion UHH (PAGNI), organized the conference, with the participation of researchers from 32 countries as well as the European Hematology Association (EHA). Ninenty (90) researchers from 22 countries participated onsite at the final conference.

The goal of the conference was to discuss and present the results of the research of the four-year Action in the field of neutropenias - in children and adults alike - the prevention of its progression into acute leukemia, to highlight the recent focus areas which have emerged and the prospects of continuing the existing collaborations and research between partners of the Action.

During the conference, young investigators had the opportunity to present their recent results on their work in the field of neutropenias, discuss with experts in the field, expand their scientific network and promote further collaborations between research Institutions and hospitals across Europe.

Particularly important is the Common EU Guidelines on the diagnosis and Management of

Neutropenia jointly published by EUNET-INNOCHRON and the European Hematology Association, for the benefit of patients, their families and caretakers and practicing clinicians.

This publication focuses on neutropenia overall, and only touches on SDS superficially. However, it encourages genetic testing to include SDS and other genetic causes of neutropenia and references other important articles.

Patient representatives were also present and provided their perspectives, helping redefine therapeutic goals while providing insights on their expectations.

On behalf of the SDS patient and advocacy community, the SDS Alliance would like to express our sincere gratitude for the opportunity to participate in this important action, community, and meeting.

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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!

An exploration of the experiences of siblings of people with a diagnosis of Shwachman-Diamond Syndrome

Living with a sibling who has a rare disease like Shwachman-Diamond Syndrome (SDS) can be a complex experience for the unaffected sibling(s). While they may not have the same physical symptoms or medical needs, the emotional impact can be significant and often introduce unique challenges to the family dynamic. Despite not having SDS themselves, the unaffected sibling's life is inevitably shaped by its presence, leading to a complex mix of emotions that require understanding and support from those around them. Other studies investigating the experience of siblings to individuals with inherited bone marrow failure syndromes such as Fanconi anemia have been published, but the experience of unaffected siblings to those with SDS have not been specifically explored… until now! 

In our SDS & Science Snapshot this week, we are happy to share a new research opportunity exploring the experiences of siblings to individuals with SDS. This study is being led by Amy Doyle, a family therapy trainee at the University of Exeter in England, United Kingdom.

Here is what Amy, the lead researcher, shared about the importance of this study and how to get involved:

What is the purpose of this study?

The aim for this study is to learn more about the experiences of siblings to individuals with SDS from childhood to adulthood and to highlight the potential value in and usefulness of additional support such as therapy for families of people experiencing SDS.

What is your inspiration for leading this study?

I have an interest in and awareness of SDS due to a personal, family connection. In reviewing the current research and learning more about other chronic illnesses, I have recognized that the majority of support that is currently available is for affected individuals. I recognize and am learning that conditions like SDS have an impact on the whole family system and hope that this study can provide insight on this experience.

Who is eligible to participate?

Individuals who meet the following criteria are eligible to participate:

• Siblings to individuals with a diagnosis of SDS

• Adult participants at least 18 years of age

• Must be able to speak English

• Access to a computer, internet, and video-conferencing 

How is this study being conducted?

Participants will be asked to answer a brief demographic survey online with questions about age, gender, ethnicity, geographical location, and education level. Following this survey, the lead researcher will conduct individual interviews online via Microsoft Teams. It is anticipated that the interviews will take no longer than one hour. These interviews will be recorded and transcribed by the lead researcher. The interview transcripts will be anonymised and analyzed.

What kind of questions will be asked?

Questions asked of participants will be particularly centered around individuals’ experiences as siblings, and to explore the impact that SDS has had on their lives as individuals and as a family. Questions will also consider the support that has been offered and is available, as well as what may or may not have been helpful for them and their families.

What will happen to the results of this research study?

The results of this research study will be analyzed and written up as part of the lead researcher’s final dissertation project. The lead researcher hopes to present the results of this study to the trustees of the Shwachman-Diamond Syndrome UK charity and potentially publish the results in a relevant journal.

Who is overseeing this research?

This research is being conducted as part of the lead researcher’s final dissertation at the University of Exeter. The researcher’s tutor Kate Campbell is overseeing the research.

The Data Controller for this research is the University of Exeter. Ethical approval for this research has been granted by the University of Exeter’s CEDAR psychology ethics committee.

How do I get involved?

If you are eligible or know someone who is, please don't hesitate to get in touch with me by emailing me at ad903@exeter.ac.uk. I can share my participant information sheet with you and answer any questions that you have.

Resources for Siblings to Individuals with a Rare Disease:

• The Sibling Support Project: https://siblingsupport.org/

• Sibling Leadership Network: https://siblingleadership.org/

• Rare Sibling Stories: https://linktr.ee/raresiblingstories

Stay tuned to our SDS & Science Snapshot series next week to learn more about a new study which published growth charts specific for individuals with SDS!

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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!

The Importance of Germline Genetic Testing for Patients with Bone Marrow Failure and Related Disorders

Between March 21-22, 2024, the Aplastic Anemia and Myelodysplastic Syndrome International Foundation (AAMDSIF) hosted the 9th International Bone Marrow Failure Disease Scientific Symposium in Bethesda, MD, USA. This meeting brought together experts from around the world to discuss the latest advances in both the science and patient care for these disorders. The first session at the Scientific Symposium highlighted the role of genetic testing for persons with bone marrow failure, and led to a lively discussion on when, whom, and what genetic testing should be offered.

We reached out to Dr. Lisa J. McReynolds, a leading physician-scientist studying inherited bone marrow failure syndromes (including Shwachman-Diamond Syndrome!) and the first speaker at this Scientific Symposium, to bring you an exclusive summary of their thoughts on the importance of genetic testing for individuals with bone marrow failure.

Here is what they shared:

Shwachman-Diamond Syndrome (SDS) is part of a group of disorders that are often collectively called “inherited bone marrow failure syndromes (IBMFS).” This is because what unites all IBMFS is that they can be genetic (or inherited, passed from parent to child in the genes) and can cause a person’s bone marrow to “fail”, stop working, or malfunction. It can be very difficult to sort out which form of bone marrow failure a person has. This problem is made worse by the fact that other disorders that are not genetic can look a lot like an IBMFS. Two of these disorders are aplastic anemia (AA) and myelodysplastic syndrome (MDS). AA is caused by an immune attack on the person’s bone marrow leading to it to not function. MDS is a form of blood cancer that under the microscope can look like an IBMFS.

There are some laboratory tests that can help sort out IBMFS (and which specific type) versus AA versus MDS, but they can be insufficient to get a final diagnosis. One of the best tools healthcare providers have to reach an accurate diagnosis is genetic testing.

This SDS & Science Snapshot published last fall helps explain the role of genes in developing diseases such as AA or MDS and the difference between somatic and germline mutations. Additionally, the SDS Science Spotlight YouTube video below also explains how individuals with SDS are at-risk of developing bone marrow failure or leukemia and how this relates to the genetics of SDS.

So, why should people with bone marrow failure, such as individuals with SDS, have genetic testing? 

1. The signs of a genetic disorder can be subtle or absent when a person comes to the attention of a healthcare provider, and there is often no family history of a genetic disease. 

2. About 5% of all patients with bone marrow failure have a genetic reason for their disease. This number is critical since many professional societies recommend genetic testing for diseases with a greater than 5% chance of being genetic.

3. Uncovering a genetic cause for the person with bone marrow failure can lead to changes in treatment planning and screening recommendations moving forward.

4. Genetic testing results may also change who is chosen as a donor if the person plans to have a bone marrow transplant. 

5. Genetic testing results can also help guide potential genetic testing of other family members. 

There are several different types of genetic testing that can be done for SDS and other bone marrow failure diseases, such as panel testing or exome sequencing (this SDS & Science Snapshot published a few weeks ago reviews genetic testing for SDS in more detail). The choice of testing is best determined by your genetic counselor and physician. However, getting genetic testing can be challenging for some patients. One of the biggest challenges many patients face is insurance coverage. Many insurance companies do not cover the testing and if it is covered it can be insufficient or come with large out-of-pocket costs. This has unfortunately led to inequities across our bone marrow failure community with some patients being able to access genetic testing and others not. Healthcare providers need to advocate for all bone marrow failure patients to receive genetic testing as recommended.

To help address these inequities, Shwachman-Diamond Syndrome Alliance is committed to increasing access to no-cost clinical genetic testing for individuals suspected of having SDS and providing opportunities to participate in research for those with previous negative or uninformative genetic testing results. 

Stay tuned to our SDS & Science Snapshot series this Spring to learn more about genetic testing resources that may be helpful for your family! Or, reach out to us directly via email at genetics@SDSAlliance.org. We are here to help!

The team at SDS Alliance would like to extend a warm message of appreciation to Dr. Lisa J. McReynolds for their contributions to this SDS & Science Snapshot and, more importantly, for leading critical research efforts for individuals with IBMFS such as SDS!

AAMDSIF Resources: 

The AAMDSIF has published several Patient Guides and Fact Sheets (available in multiple languages including Italian, French, German, Spanish, and Portuguese!) for understanding acute myeloid leukemia (AML), MDS, and AA on their website!

These toolkits published by AAMDSIF answer some of your most important questions about Aplastic Anemia and Myelodysplastic Syndrome!

AAMDSIF also hosts Patient and Family Conferences for individuals who have been diagnosed with and/or survived AA, MDS, AML - visit their website for a list of these events happening this year across the United States in Los Angeles, Seattle, Philadelphia, Chicago, and Tampa.

Disclaimer: The views and opinions expressed in this SDS & Science Snapshot only reflect those of Lisa J. McReynolds, MD, PhD.

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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!

BeginNGS: Newborn Genomic Sequencing to End the Diagnostic Odyssey

Two weeks ago, a new podcast episode of Once Upon a Gene was released highlighting BeginNGS, a ground-breaking initiative at Rady Children’s Institute for Genomic Medicine (RCIGM) that is helping to rewrite the story for infants with rare diseases (including Shwachman-Diamond Syndrome!).

We reached out to Dr. Jennifer Schleit, Laboratory Director at RCIGM, to bring you an exclusive summary on how advances in genetic testing technology are changing newborn screening methods and the course of the diagnostic odyssey in rare disease.

Here is what they shared:

Newborn screening (NBS) is a public health program aimed at testing babies for genetic conditions that are treatable, but may not be apparent at birth. Through early diagnosis, affected children can receive appropriate monitoring and treatments to reduce the negative impacts of these disorders and improve survival rates. (For more information about the economic impact of a delayed diagnosis, you can read this recent SDS & Science Snapshot). Currently, NBS programs are active in all 50 states and it is estimated that approximately 98% of babies born in the United States will be tested in the first two days of life. An interactive timeline showing the evolution of newborn screening methods is published on the BeginNGS website.

For more information about traditional newborn screening and what conditions are screened for across the United States, you can visit this website, Baby’s First Test.

How are advances in genetic testing technology changing newborn screening?

Current NBS programs primarily use laboratory methods such as mass spectrometry or enzyme activity to perform the screening in babies These methods have been successful, however they limit the number of disorders that can be tested, as only those disorders that can be detected with these testing methods can be included in current screening programs. Recent advances in genome sequencing, including reduced sequencing costs and faster sequencing time, have led to this technology being considered as a new testing method in NBS. Genome sequencing allows for more disorders to be tested simultaneously.

The SDS & Science Snapshot published a few weeks ago helps explain why genetic testing for SDS is important and how you can access it.

What is BeginNGS?

BeginNGS is a pilot project based out of Rady Children’s Institute for Genomic Medicine (RCIGM) to use genome sequencing to screen newborns for over 400 early onset, actionable disorders (including Shwachman-Diamond Syndrome!). RCIGM is a world leader in ultra-rapid and rapid genome testing, making it uniquely positioned to deliver NBS results in a timely manner. This project is currently based at Rady’s Children’s Hospital in San Diego, California. The BeginNGS team is actively planning to expand this trial to include additional health systems to enable participation from more geographic areas.

How are disorders selected or BeginNGS?

Candidate disorders were identified by reviewing clinical diagnostic testing of over 4000 critically ill newborns and children at RCIGM, by reviewing lists of expanded NBS disorder lists developed by other groups, and by evaluating publications which reported interventions for these disorders. Selected disorders were then evaluated by a team of medical and genetics professionals. Disorders included in BeginNGS met the following criteria:

• They had acute, childhood admission that were likely to lead to hospital admission

• A treatment was available for the disorder

• It is a single-locus genetic disorder, inherited defects in a single gene can cause disease

• There is a high likelihood of rapid disease progression without treatment

• The disorder can be diagnosed by genome sequencing

Additional disorders could be added to BeginNGS as they are discovered and/or new treatments become available.

The team at SDS Alliance would like to extend a warm message of appreciation to Dr. Jennifer Schleit and the BeginNGS team for blazing trails in the newborn genomic sequencing space, shortening the diagnostic odyssey for individuals and families in the SDS community.

SDS Alliance looks forward to sharing the results of the BeginNGS initiative with the SDS community in future SDS & Science Snapshots.

For more detailed information about how Rady Children’s Institute for Genomic Medicine plans to change the landscape of newborn screening with whole genome sequencing, you can read their manuscript published in the American Journal of Medical Genetics.

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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!

The last few weeks have brought us three different case reports published in the biomedical literature, each highlighting a different aspect of the disease.

A case report of a young patient with SDS whose diagnosis was nearly missed

This case report shares the story of a young patient with SDS whose diagnosis was nearly missed due to inconsistent genetic test results and liver issues not always recognized as typical for SDS.

Initially, the patient was thought to have a rare, genetic liver disease or mitochondrial disease. The authors describe in great detail their findings regarding the liver of the patient, such as electron microscopy imaging of the inside structure of liver cells, including mitochondria. Note, that the ribosomes in the mitochondria (a.k.a. mitoribosomes) are structurally different and responsible for translating genetic information encoded in mitochondrial DNA. These ribosomes are NOT involved in SDS, but can cause mitochondrial diseases if there is a defect. Mitochondria are organelles responsible for converting energy from food into ATP, the chemical energy our cells need to live and thrive. Check out our blog post on ribosomes and mitochondria, here. The authors report:

As we all know, SDS is a rare genetic syndrome characterized by multiorgan dysfunction with typical presenting features that include exocrine pancreatic, hematologic, and skeletal abnormalities. It is now also established that the liver is often affected. However, the long-term implications are not known, and there is no treatment available for the frequently reported highly elevated liver enzymes (transaminases) in young children. We know from the SDS patient community that many patients undergo liver biopsy before being diagnosed with SDS, with no clinically actionable outcomes. For most patients, the liver enzyme levels go back down into (or close to) normal levels within the first 5 years of life. The authors report:

We believe that this assumption warrants further investigation, as there is very little data available about adult SDS patients' overall health. Despite the high prevalence of highly elevated liver enzymes in early childhood, very little is known about the condition. There is a high need for research in this area.

The genetic workup of the child has not been straightforward, either. Whole exome sequencing (WES) initially missed the diagnosis. The authors looked into why. They think that it is either because not all the relevant symptoms were listed in the WES test request, and therefore the SDS genes may not have received the proper attention at the data interpretation step by the testing company, or perhaps there was a problem with the test analytics due to the SBDS pseudogene SBDSP1. Check out our blog post on pseudogenes to learn more. The authors report:

The full article is available here:

A success story of treating an SDS patient with AML in China

One of the biggest concerns we face as SDS patients and caregivers is the risk of developing leukemia, specifically acute myeloid leukemia, or AML for short. The risk is estimated to be around 30% by age 30, which keeps on going up after that. AML develops when the blood-forming stem cells in the bone marrow accumulate new mutations (also known as somatic mutations) that allow them to grow out of control. We have covered the mechanism of this in an educational video, here.

To make matters worse, AML in SDS patients often contains p53 mutations, which makes its treatment even harder than it already is. Combined with the increased sensitivity to chemotherapy that would be needed to get rid of AML, there are very few success stories of a positive outcome.

The medical and scientific community is hard at work trying to find better treatment options for AML, for both the general population and for SDS patients, as highlighted at many scientific conferences, including the AA-MDS Symposium which our team attended just last week. More about that soon.

Today, we want to highlight a brand new case report from Beijing, China, in which the authors report success in treating one SDS patient who developed AML. The approach was to treat the AML first to reduce the number of AML cells, in order to increase the likelihood of success for hematopoietic stem cell transplant. This is not a new approach, and many groups are looking for a good combination of chemotherapeutic drugs that can work for SDS. It seems that for this particular patient, they found something that worked. The authors report:

At the time of this article, the patient has been 6 months post-transplant and well. We wish the 15 year-old-patient continued health and recovery.

We have reached out to the authors to learn more and will update this blog post if new information becomes available.

Azacitidine combined with venetoclax alleviates AML-MR with TP53 mutation in SDS: a case report and literature review.

Ma C, Lang H, Chen Y, Yang L, Wang C, Han L, Chen X, Ma W.Anticancer Drugs. 2024 Mar 15. doi: 10.1097/CAD.0000000000001594. Online ahead of print.PMID: 38502829

A case of a severe, zoonic infection of a 17-year-old patient with SDS

In this recent case report, the authors share the case of a 17-year-old patient who was diagnosed with SDS as a child and treated with GCSF and PERT but lost to follow-up for several years. She came to the emergency room very ill with an acute infection, which developed into sepsis. The primary infection was identified as rat-bite fever (RBF), an important bacterial zoonosis primarily caused by Streptobacillus moniliformis in North America, but the pathogenesis is understudied.

From the information available to us about the article, it is unclear whether the patient made a full recovery or not. We have reached out to the authors to request more information and will update this blog post as we learn more.

If you or your child has SDS, please discuss with your healthcare team whether pets are safe for your household, and/or what special precautions should be taken around them. Frequent recommendations from the SDS community include being extra careful around cat litter and avoiding handing cat litter to SDS patients and any people who may be immune-compromised (such as pregnant people) to reduce the risks of toxoplasmosis.

Warning: there are disturbing images included in the original article. Viewer discretion is advised.

Oh rats! Intracellular rod-like inclusions in an adolescent with Shwachman-Diamond syndrome.

Mayhew J, Luttrell H, Barros K, Blazin L, Nichols C, Avashia-Khemka N, Lavik JP, Relich RF, Skinner D, Zhou J, Saraf A, Khaitan A.Pediatr Blood Cancer. 2024 May;71(5):e30918. doi: 10.1002/pbc.30918. Epub 2024 Feb 23.PMID: 38391125 No abstract available.

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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!

Spring into Action: Genes and Genetic Testing for SDS

On Rare Disease Day two weeks ago, we launched our "Spring into Action" campaign, with which we amplify the patient voice in SDS in order to improve patients' lives, be it through more focused, impactful research, community support, or advocacy.

Over the next few weeks and months, we will highlight multiple efforts, resources, and learning opportunities. Today, we bring you a summary of genes, genetic testing, and the importance of both in SDS.

What are genes?

Our bodies are composed of trillions of cells that have many different roles – to help us grow, digest food, protect us against infections, and more. These different tasks are controlled by a set of instructions known as genes. (We even have genes whose purpose is to protect us against cancer!) Genes are made up of DNA, which you inherit from your parents, and they determine things like your eye color, height, and even your risk for certain health conditions.

What are genetic mutations (i.e., variants)?

Sometimes there are mistakes in our genes, like a typo or error in an instruction manual or recipe book. These genetic mistakes are called mutations or variants. Shwachman-Diamond Syndrome (SDS) happens because of these genetic mistakes in certain genes including SBDS, EFL1, DNAJC21, and SRP54. These genetic mistakes are passed down from parents to kids and cause SDS.

Imagine if a sentence in a recipe book had a mistake, like telling you to turn off the oven to bake cookies. Then the cookies wouldn’t bake properly! Our cells work the same way. If there's a mistake in the genes that tell our cells what to do, our cells may have a difficult time functioning properly.

You can also watch our SDS Science Spotlight video on the Genetics of SDS to hear more about how these genetic mistakes (or mutations) contribute to the development of SDS.

What is genetic testing?

Genetic testing is the process of analyzing a gene (or more commonly, a set of genes) for these genetic mistakes that would result in SDS. Genetic testing is comparable to reading an instruction manual or recipe book very closely to identify any errors made during the writing process.

Why is genetic testing for SDS important?

Genetic testing for SDS helps your care team confirm a diagnosis of SDS and provide a clearer understanding of why you may be experiencing certain health issues. A genetic diagnosis of SDS can help guide your care team in making and following personalized treatment plans and surveillance guidelines to help you stay healthy!

What types of genetic testing are recommended for individuals with symptoms of SDS?

There are different kinds of genetic testing available for individuals who have a suspicion for SDS based on symptoms or health issues and/or a family history of SDS.

If we return to the instruction manual analogy when considering the different types of genetic testing, there are some genetic tests that only look for errors in specific sections of the instruction manual known to be associated with SDS. This type of genetic testing only looks at one or all of the known SDS/SDS-like genes, including SBDS, EFL1, DNAJC21, and/or SRP54.

There are other more thorough types of genetic testing that look for errors in the entire instruction manual, meaning all of the genes in your cells (over 20,000!) are analyzed. This kind of genetic testing can be costly and time-consuming but may provide an answer for some families as we learn more about the genetic cause(s) of SDS.

My care team has mentioned their concern for SDS, how do I access genetic testing?

If your care team has mentioned a concern for SDS, we encourage you to talk with them about your options for genetic counseling and testing. Genetic testing can be ordered by a healthcare provider such as a doctor or a genetic counselor. In the SDS community, physicians who order genetic testing for SDS frequently include primary care physicians, pediatricians, gastroenterologists, hematologists, oncologists, and many others.

For individuals in the United States, The National Society of Genetic Counselors has a Find a Genetic Counselor Tool available on their website to search for a genetic counselor local to you. We encourage you to choose the specialties of Cancer, Hematology, and/or Pediatrics to help you narrow your search for a genetic counselor.

If I have SDS myself, and my partner doesn't, can our kids get SDS?

The odds of your children getting SDS depends on your and your partner's genetic makeup. For example, let's consider SDS caused by mutations in the SBDS gene, which typically is inherited in an autosomal recessive pattern. A partner who doesn't have symptoms of SDS may be a carrier of one mutation in a gene that causes SDS or have no mutation at all. The partner with SDS will have two mutated versions of the gene, and no healthy copy. The odds of the children getting SDS will depends on all these factors and more, such as rare genetic events related to pseudogenes, for example. Check out the video embedded above. We covered the concept of pseudogenes in an earlier edition of the snapshots, and these may factor into the odds as well.

If you have a diagnosis of SDS and/or a family history of SDS, and are planning a pregnancy, you may also find it helpful to speak with a Prenatal Genetic Counselor to discuss what genetic testing might be available to help inform you and your partner on the chances of having a baby who also has SDS. For individuals in the United States, The National Society of Genetic Counselors has a Find a Genetic Counselor Tool available on their website to search for a genetic counselor local to you.

Stay tuned to our Science Snapshot series this Spring to learn more about genetic testing resources that may be helpful for your family!

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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!

Spring into Action: Joyce's Rare Disease Day Experience

Every year, on the last day of February, the international Rare Disease Community comes together to raise awareness about important policy and other issues related to rare disease. For us, every day is Rare Disease Day. Check out our updated Rare Disease Day website.

Rare Disease Day, for us, is a launch pad for our "Spring into Action" campaign, with which we amplify the patient voice in SDS in order to improve patients' lives, be it through more focused, impactful research, community support, or advocacy.

Over the next few weeks and months, we will highlight multiple efforts on how the SDS community springs into action, starting with how our community leveraged Rare Disease Day events to learn and make progress.

Today, we bring you an interview with Joyce, a young advocate living with SDS, highlighting her Rare Disease Day experience. You can learn more about Joyce’s story of living with SDS on the Rare Disease Day website where she is featured as a hero or in this 60 Seconds of RARE video published by the RARE Revolutions Magazine.

What event(s) did you participate in for Rare Disease Day and what was your motivation to participate?

Joyce: On Rare Disease Day in 2024, I participated in the Rare Disease Legislative Advocates’ Annual Rare Disease Week on Capitol Hill. Over four days we attended conferences, caucus briefings, and discussions. On February 27th, everyone had meetings with their state senate offices and representatives to share their story and introduce legislation to help them in their journey. I was motivated to participate in this event not only because of my advocacy experience and public speaking skills, but also because I wanted to share my story to help assist and guide the government into making decisions that would benefit the rare disease community. I used my experiences and knowledge to my advantage to guide the minds of those in Congress to sign-off on key legislation that would impact the rare disease community.

What was your most memorable moment from Rare Disease Day?

My most memorable moment from Rare Disease Week was meeting others with rare diseases or connecting with rare diseases and advocating together. It was such an empowering moment to be able to connect with others who have experienced similar journeys – being together in one room to advocate for similar goals. We all were encouraging and standing with each other during our meetings and events to motivate ourselves and the people around us. I very much enjoyed being able to speak up about some issues involving the rare disease community and some possible legislation that would impact the SDS community.

Did you learn anything new or gain any insights from your participation in Rare Disease Day events?

I learned a lot this year on Rare Disease Week. I learned how to gain a stronger understanding of how to tell my story, and what details to share when speaking with government officials. I learned how I can incorporate my experience and journey with SDS into advocating for certain bills for the rare disease community as a whole. I gained insight from fellow peers, advocates, and leaders in the rare disease community about the diagnostic odyssey of rare disease patients and what each individual is doing to help us as a community. I learned how to transform my public speaking skills into a motivational day full of business and fun. Plus a fun little perk of attending this event is that I learned how to navigate my way through the US House of Representatives and Senate buildings through underground tunnels.

How do you plan to continue advocating for SDS and other rare diseases beyond Rare Disease Day?

I plan to continue to be an active member of the Rare Disease Legislative Advocates this year, speaking out for legislation for the rare disease community. This year I plan to be an active Young Adult Rare Representative as I enter my 16th year of life. I plan to continue to use my experience of living with a rare genetic disorder to further expand the knowledge of those around me about SDS and the problems surrounding our community. By using my story, I can have solid backing for my proposals to the congressmen and women, giving them a personal connection to the legislation. I also plan to continue to post on my SDS Instagram account @cure.sds, to provide information on the disease and what daily life looks like.

What advice would you give to others who are interested in getting involved in advocacy efforts for Rare Disease?

The advice I give to others is always to use their past experiences and traumas to their advantage in the field of advocacy. Use your insight and knowledge of living with or caring for someone with a rare condition to be able to speak up against the issues in the rare disease community. I always tell people they should not fear their disease and instead make it a part of them. In advocacy work, it is key to embrace your disorder to truly be able to speak out and stand up for what is right. By using your story, you can catch the eyes of people who may have never heard of your disorder and are willing to help. If you are just entering into the advocacy space, I recommend starting small, creating a social media platform to raise awareness and give insight into the common problems and daily life of living with a rare disorder. Never stop because something goes wrong, use that negative event as further inspiration to keep thriving as an advocate and as a human being. Not everything is going to go your way all the time, there will be some bumps in the road, so turn that negativity into strength.

On behalf of our team at SDS Alliance - Joyce, we thank you for your hard work, dedication, and passionate advocacy for the SDS community on Rare Disease Day and everyday! We are grateful to have you as a member of our community and can't wait to see how you transform the lives of so many living with a rare disease.

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Check out our new SDS infographics (available in English and Spanish/Español)!

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If you’re interested in viewing some of this year’s Rare Disease Day events, many of them were recorded and are now available to stream online:

• The White House: Rare Disease Forum

• Broad Institute of MIT and Harvard: Rare Disease Day 2024: Climbing Ladders to Cures in Rare Disease Research

• National Institutes of Health (NIH): Rare Disease Day Event

• US Food and Drug Administration (FDA): FDA's Rare Disease Day 2024—Dedicated to Patients and Providers

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Actúe: la experiencia del Día de las Enfermedades Raras de Joyce

En este número: Preguntas y respuestas con un defensor de SDS: ¿Qué estaban haciendo el Día de las Enfermedades Raras?

Cada año, en el último día de febrero, la comunidad internacional de enfermedades raras se reúne para crear conciencia sobre políticas importantes y otras cuestiones relacionadas con las enfermedades raras. Para nosotros, cada día es un día de Enfermedad Rara.

Para nosotros, el Día de las Enfermedades Raras es una plataforma de lanzamiento para nuestra campaña "Actúe en primavera", con la que amplificamos la voz de los pacientes en SDS para mejorar sus vidas, ya sea a través de investigaciones más enfocadas e impactantes, apoyo comunitario o abogacía.

Durante las próximas semanas y meses, destacaremos múltiples esfuerzos. Hoy les traemos un resumen de cómo nuestro equipo aprovechó los eventos del Día de las Enfermedades Raras para aprender y progresar. Le preguntamos a Joyce, una joven defensora que vive con SDS, sobre su experiencia en el Día de las Enfermedades Raras. Puede obtener más información sobre la historia de Joyce sobre cómo vivir con SDS en el sitio web del Día de las Enfermedades Raras, donde aparece como una heroína o en este video de 60 Seconds of RARE publicado por la revista RARE Revolutions.

¿En qué eventos participó para el Día de las Enfermedades Raras y cuál fue su motivación para participar?

Joyce: En el Día de las Enfermedades Raras de 2024, participé en la Semana Anual de Enfermedades Raras de los Defensores Legislativos de Enfermedades Raras en Capitol Hill. Durante cuatro días asistimos a conferencias, reuniones informativas y discusiones. El 27 de febrero, todos se reunieron con las oficinas y representantes del senado estatal para compartir su historia y presentar legislación que los ayude en su viaje. Me motivó a participar en este evento no solo por mi experiencia en defensa de derechos y mis habilidades para hablar en público, sino también porque quería compartir mi historia para ayudar y guiar al gobierno en la toma de decisiones que beneficiarían a la comunidad de enfermedades raras. Utilicé mis experiencias y conocimientos a mi favor para guiar las mentes de los miembros del Congreso para aprobar una legislación clave que afectaría a la comunidad de enfermedades raras.

¿Cuál fue tu momento más memorable del Día de las Enfermedades Raras?

Mi momento más memorable de la Semana de las Enfermedades Raras fue conocer a otras personas con enfermedades raras o conectarme con enfermedades raras y abogar juntos. Fue un momento muy enriquecedor poder conectarme con otras personas que han experimentado viajes similares: estar juntos en una sala para abogar por objetivos similares. Todos nos animamos y nos apoyamos unos a otros durante nuestras reuniones y eventos para motivarnos a nosotros mismos y a las personas que nos rodean. Disfruté mucho poder hablar sobre algunos temas que involucran a la comunidad de enfermedades raras y algunas posibles leyes que afectarían a la comunidad SDS.

¿Aprendió algo nuevo u obtuvo alguna información a partir de su participación en los eventos del Día de las Enfermedades Raras?

Aprendí mucho este año en la Semana de las Enfermedades Raras. Aprendí a comprender mejor cómo contar mi historia y qué detalles compartir al hablar con funcionarios del gobierno. Aprendí cómo puedo incorporar mi experiencia y mi trayectoria con SDS para defender ciertos proyectos de ley para la comunidad de enfermedades raras en su conjunto. Obtuve información de colegas, defensores y líderes de la comunidad de enfermedades raras sobre la odisea diagnóstica de los pacientes con enfermedades raras y lo que cada individuo está haciendo para ayudarnos como comunidad. Aprendí cómo transformar mis habilidades para hablar en público en un día motivador lleno de negocios y diversión. Además, una pequeña ventaja divertida de asistir a este evento es que aprendí a navegar a través de los edificios de la Cámara de Representantes y del Senado de los Estados Unidos a través de túneles subterráneos.

¿Cómo planea continuar abogando por el SDS y otras enfermedades raras más allá del Día de las Enfermedades Raras?

Planeo seguir siendo un miembro activo de los Defensores Legislativos de Enfermedades Raras este año, defendiendo la legislación para la comunidad de enfermedades raras. Este año planeo ser un Representante Raro de Adultos Jóvenes activa al cumplir 16 años de vida. Planeo seguir utilizando mi experiencia de vivir con un trastorno genético poco común para ampliar aún más el conocimiento de quienes me rodean sobre el SDS y los problemas que rodean a nuestra comunidad. Al utilizar mi historia, puedo tener un respaldo sólido para mis propuestas a los congresistas, brindándoles una conexión personal con la legislación. También planeo seguir publicando en mi cuenta de Instagram de SDS @cure.sds, para brindar información sobre la enfermedad y cómo es la vida diaria.

¿Qué consejo le daría a otras personas interesadas en participar en esfuerzos de defensa de las enfermedades raras?

El consejo que doy a los demás es siempre que utilicen sus experiencias y traumas pasados ​​a su favor en el campo de la defensa. Utilice su visión y conocimiento sobre cómo vivir con alguien con una enfermedad rara o cuidar de ella para poder hablar en contra de los problemas de la comunidad de enfermedades raras. Siempre les digo a las personas que no deben temer a su enfermedad y, en cambio, hacerla parte de ellos. En el trabajo de promoción, es clave aceptar su trastorno para poder verdaderamente hablar y defender lo que es correcto. Al utilizar su historia, puede captar la atención de personas que tal vez nunca hayan oído hablar de su trastorno y estén dispuestas a ayudar. Si recién está ingresando al espacio de la defensa, le recomiendo comenzar poco a poco, creando una plataforma de redes sociales para crear conciencia y brindar información sobre los problemas comunes y la vida diaria de vivir con una enfermedad rara. Nunca te detengas porque algo sale mal, utiliza ese evento negativo como inspiración adicional para seguir prosperando como defensor y como ser humano. No todo va a salir como quieres todo el tiempo, habrá algunos obstáculos en el camino, así que convierte esa negatividad en fuerza.

En nombre de nuestro equipo en SDS Alliance - Joyce, le agradecemos su arduo trabajo, dedicación y defensa apasionada de la comunidad SDS en el Día de las Enfermedades Raras y todos los días. Estamos agradecidos de tenerla como miembro de nuestra comunidad y estamos ansiosos por ver cómo transforma las vidas de tantas personas que viven con una enfermedad rara.

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¡Mira nuestras nuevas infografías sobre SDS (disponibles en inglés y español)!

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Paula shared their story beautifully in a detailed blog on the "Extra Lucky Moms" blog. Check it out!

Below, with Paula's permission, we are sharing some short excerpts.

"When Alex was five months old, he caught a cold. I watched as his little chest keep rising and falling. Then I could see his ribs and collar bone as he tried to suck in air. Something was wrong. His breathing was extremely labored. I rushed him to the emergency room. They immediately took him to a triage room. While they were examining him, I watched as my baby stopped breathing completely. It felt like time stopped, and it may have only lasted about 20 seconds in reality, but it was enough time for his entire body to turn this awful dark purple color. From head to toe, he was the color of an eggplant. I remember looking at the nurse and finally saying “Do something, he’s not breathing!”

"After Alex’s ankle surgery [for a serious infection], one of the doctors recommended we see a genetic specialist. She was the first doctor to look at his entire medical history and suggest that there might be something that ties all of his seemingly random medical events together. So, we made an appointment with another specialist and more tests were done. Alex kept getting sick, coming down with colds, having labored breathing, and having to go to the emergency room. We were at the emergency room or at a doctor’s office almost every two to four weeks. We were hoping for some answers. 

While we waited for his genetic test results to come back in, our pediatrician noticed that Alex was flapping his hands a lot at one of his appointments. He would also occasionally walk on his toes. She started to ask me questions about his speech and his vocabulary. I shared this his vocabulary was limited but I attributed that to all the time he has been spending in the hospital. Then she hit me with something I was not expecting. She recommended we see a behavioral pediatrician to have him evaluated for Autism Spectrum Disorder. He did so many things well that once again, I naively believed that this would simply be an evaluation to check this off the list and rule it out. So, another appointment with another specialist was made.

Then came the two weeks in October of 2020 that I will never forget. First, I received the call from the genetics office. They had Alex’s test results in and confirmed that he had a very rare genetic disorder called Shwachman Diamond Syndrome. All the person from the genetics office could tell me about it was that it is a bone marrow disorder and that I needed to make a follow up appointment with the hematology and oncology team at the children’s hospital. I had so many questions but she could not answer any of them because it was not her specialty. Her job on that call was just to deliver the diagnosis, not provide any answers. So like anyone would do, I went to the internet. And this is when my heart broke again. Shwachman Diamond Syndrome is a bone marrow disease that impacts every single system of the body."

Read the full story on the "Extra Lucky Moms" blog, here.

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!

An update on the development of Ataluren, a therapeutic approach targeting the c.183_184TA>CT mutation in the SBDS gene

Over the past few years, important research has been ongoing in Dr. Valentino Bezzerri and Dr. Marco Cipolli’s laboratory in Italy to investigate the use of Ataluren to treat individuals with SDS. We previously wrote about this work, including a detailed summary by Dr. Bezzerri in a SDS & Science Snapshot edition from May 2022 and October 2023.

This week, the publication has finally hit the shelves and is now available for free online. It expands the pre-clinical laboratory based research to solidify the rationale to enable clinical trials for Ataluren for a subset of SDS patient. The authors show, that

• Ataluren improved ribosome assembly and total protein synthesis in SDS-patient-derived cells in the lab

• Restored myelopoiesis in myeloid progenitors in the lab

• Improved neutrophil chemotaxis in an experimental model

• Reduced neutrophil dysplastic markers in the lab.

• Restored full-length SBDS protein production in osteoblasts (bone producing cells) donated by patients, suggesting that its beneficial role may go beyond the blood producing stem cells.

Dr. Bezzerri also shared his work at the 2023 SDS POPS summit in May and joined us for a lively discussion at our first ever Ask-an-Expert Community Chat. It was fantastic. Check out the recording, below.

As previous highlighted, the group tested the effect of Ataluren in the laboratory on cells of individuals with SDS who harbor the c.183_184TA>CT mutation in their SBDS gene. These preclinical studies showed:

1. Improved SBDS protein levels and improved ribosome assembly and total protein synthesis;

2. Reduced the elevated levels of p53 protein, which is found in excess in SDS tissues; and

3. Improved migration of neutrophils, important cells in the immune system frequently reduced in individuals with SDS.

These results are promising for Ataluren and its use as a "personalized medicine" approach for treating SDS patients carrying nonsense variants, such as c.183_184TA>CT. These preclinical results support the idea of developing of a Phase I/II clinical trial in the future for Ataluren in SDS patients who have a nonsense mutation. The SDS Alliance team will remain in communication with the SDS community about these trials when/if they become available. Be sure to sign up for updates!

The figure below summarizes the findings published in the current article. The top of the figure shows what normally happens in SDS cells that harbor a nonsense variant. The bottom panel shows the mechanism of Ataluren and the improvements it makes on the cellular environment.

What is the significance of the c.183_184TA>CT mutation in SBDS gene?

A large percentage of SDS patients carry the variant (i.e., mutation), c.183_184TA>CT, in addition to the most common “splice site” variant. For instance, the c.183_184TA>CT variant is present in more than half of SDS patients. This genetic change leads to the generation of a premature stop in building the SBDS protein, similar to inserting a period in the middle of a sentence. These types of variants, known as nonsense variants, generally result in unstable protein intermediates and are rapidly degraded in the cell or produce a protein that has lost its function.

What is Ataluren?

Ataluren (PTC124) was launched in 2007 by PTC Therapeutics (NJ, USA), which promotes careful attention to “incorrect punctuation” in cells (e.g., an extra period in the middle of a sentence). This attention allows for more selective synthesis of proteins with normal structure (i.e., proteins without the extra period in the middle of the sentence). Furthermore, Ataluren has shown less toxicity and better safety than other drugs used for similar purposes. The use of Ataluren as a potential therapeutic agent for genetic disorders has been proposed for the treatment of Duchenne Muscular Dystrophy (DMD) and Cystic Fibrosis (CF). Most importantly, Ataluren has been approved for the treatment of DMD in Europe (but not in the US). Data from clinical trials showed that chronic Ataluren treatment is beneficial to DMD patients undergoing standard care, because it delays the progression of ambulation impairment and the worsening of pulmonary and cardiac functions. Interestingly, clinical studies revealed that the best results are observed in younger individuals, suggesting major benefits of early ataluren administration.

Why is Ataluren not widely used?

Despite promising pre-clinical results, Ataluren unfortunately failed in clinical studies for CF and was therefore discontinued. This early work suggested there may be highly variable clinical benefits in using Ataluren to treat individuals with CF. Because of such variable levels of effectiveness of Ataluren, it is important to perform extensive preclinical testing using cells in the laboratory, such as the recent work published by Cipolli et al., before trying Ataluren in people with SDS in clinical trials.

Find additional information about Ataluren and its treatment of individuals with DMD by watching this YouTube video.

Ataluren improves myelopoiesis and neutrophil chemotaxis by restoring ribosome biogenesis and reducing p53 levels in Shwachman-Diamond syndrome cells.

Cipolli M, Boni C, Penzo M, Villa I, Bolamperti S, Baldisseri E, Frattini A, Porta G, Api M, Selicato N, Roccia P, Pollutri D, Marinelli Busilacchi E, Poloni A, Caporelli N, D'Amico G, Pegoraro A, Cesaro S, Oyarbide U, Vella A, Lippi G, Corey SJ, Valli R, Polini A, Bezzerri V.Br J Haematol. 2024 Jan;204(1):292-305. doi: 10.1111/bjh.19134. Epub 2023 Oct 24.

PMID: 37876306

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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!

Share Your Colors on Rare Disease Day!

WHAT IS RARE DISEASE DAY? 

Rare Disease Day is the official international awareness-raising campaign for rare diseases, observed annually on the last day of February. The primary goal of this campaign is to increase awareness among the general public and decision-makers about rare diseases and their influence on the lives of families living with these conditions. 

Rare Disease Day was launched by EURORDIS Rare Diseases Europe and its Council of National Alliances in 2008. EURORDIS continues to lead the international campaign with a global patient community. Patient organizations from North America joined in 2009, followed by all continents by 2010. National Alliances, such as the Nation Organization for Rare Disorders (NORD) in the United States, ensure Rare Disease Day coordination at a national level, collaborating with local patient organizations and often organizing national events targeting policymakers. The number of participating countries has grown annually, with thousands of events now occurring on all continents in or around February. Since 2008, events have been held in over 100 countries.

Fun Fact: You can virtually attend the NIH Rare Disease Day Event with SDS Alliance! Our Genetics Project Manager, Ashley Thompson, MS, CGC will be attending this event in-person to represent SDS Alliance and the SDS community this coming week. Stay tuned for our Snapshot next week for updates on these events and others!

CELEBRATE THE UNIQUENESS OF BEING RARE 

With over 300 million people globally living with a rare disease (and an estimated 5000 individuals with SDS in the US and Europe), we join hands with you across borders and amidst the 6000+ rare diseases to advocate for equitable access to diagnosis, treatment, care, and social opportunities. 

The key message for Rare Disease Day 2024 is SHARE YOUR COLORS! 

Here are some ways to get involved in this year's campaign: 

1.GET INVOLVED ON SOCIAL MEDIA

Share your Rare Disease Day event videos - such as the timeless video we created for SDS, below - and photos on social media using #RareDiseaseDay and tag @rarediseaseday. You can also express your support for those living with rare diseases in your community by sharing a photo with painted hands on social media.

Explore the Rare Disease Day website for downloads including images, profile picture frames, Instagram filters, and Zoom backgrounds, and more that you can use on social media!

Use crucial rare disease statistics to convey that while each disease may be rare, collectively, they impact a vast number of people.

• 300 million people worldwide live with a rare disease.

• There are over 6000 different rare diseases.

• 72% of rare diseases are genetic.

• 70% of these genetic rare diseases begin in childhood. 

• There are an estimated 5000 individuals living with SDS in the US and Europe, and many more are undiagnosed!

2. ORGANIZE AN EVENT! 

Every year, thousands of events across over 100 countries commemorate Rare Disease Day. Most events will be online, allowing people worldwide to participate. 

Plan an online event in or around February for Rare Disease Day to heighten awareness of rare diseases in your community. Here are some successful ideas from global organizers: 

• Illuminate your home for Rare Disease Day: see the Light Up for Rare Toolkit for more information.

• Raise awareness on Facebook and Instagram Live, and invite your friends.

• Hold an art, photography, or essay-writing competition.

• Organize a walk.

• Plan a sporting event.

• Present your story to your local authorities.

3. BECOME A FRIEND

Become a Rare Disease Day friend to showcase your organization or company’s support for the campaign! Simply fill in your details to create a profile page on the Rare Disease Day website. This will display your commitment to supporting people living with a rare disease. 

4. TELL YOUR STORY!

Raise awareness about rare diseases and their impact on people’s lives by sharing your personal experience of living with SDS or caring for someone who does. Submit your written or video testimony on the Rare Disease Day website and explore stories already shared by others!

5. TAKE ACTION LOCALLY

In addition to organizing events, you can act locally in your country, region, or area to raise awareness of rare diseases! On Rare Disease Day, we advocate for equity for people living with a rare disease worldwide. 

CONTACT THE PRESS 

Reach out to local or regional newspapers and radio stations to cover your Rare Disease Day event. Send out a press release to your area’s media, highlighting the issues most crucial to rare disease patients in your country. Watch the webinar ‘How to Use Rare Disease Day to Advance Your Advocacy Objectives’ to learn the basics!

GET POLITICAL 

Write to key decision-makers about the pressing issues facing rare disease patients in your country, urging them to prioritize rare diseases! Advocate to policymakers for equitable access to diagnosis, treatment, care, and social opportunities for those living with a rare disease. For guidance on advocating for rare diseases within Universal Health Coverage, refer to the Rare Disease Day Equity Toolkit. 

Invite politicians to your organization, to an event you’re hosting, or to a rare disease research lab. If you live in Europe, encourage your MEP to join the Parliamentary Advocates for Rare Diseases Network. If you live in the United States, register for Rare Disease Week on Capitol Hill hosted by the Rare Disease Legislative Advocates.

7. DOWNLOAD COMMUNICATION MATERIALS

The official Rare Disease Day communication materials and logo are freely available for your Rare Disease Day events' promotion. Materials available in Mandarin, English, Arabic, Spanish, Portuguese, French, Hindi, and Russian. 

Also available for download: 

• The official Rare Disease Day logo

• Website countdown

• Rare Disease Day style guide

• Fonts

• Webinar toolkits.

If you, your friends, family, and colleagues take part in Rare Disease Day, don’t forget to share your photos from activities worldwide by uploading them to the Rare Disease Day website! We cannot wait to see how the SDS community lights up for rare this week!

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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 Clinical Research: A Global Perspective

As we honor Black History Month in the United States, it's essential to recognize the importance of diversity in clinical research and trials. Diversity in this context refers to including people from all walks of life – different races, ethnicities, backgrounds, and countries – in research studies. Why does this matter for those of us in the rare disease community?

Embracing individuals from diverse backgrounds in clinical research is fundamental for advancing medical knowledge and improving healthcare outcomes worldwide. When clinical trials include people from diverse backgrounds, it helps scientists understand how treatments work for everyone. Every person is unique, and factors like where they live, their genes, and their culture can affect how they respond to treatments. By including a wide range of people in research, scientists, physicians, and other researchers can make sure that treatments are safe and effective for everyone, including those with rare diseases.

Below is a video from a session at the 2023 Global Genes RARE Health Equity Forum: Understanding the Patient Perspective – How to Ensure Diverse Patient Participation in Clinical Trials and Research. In this session, the panelists discuss how patients can/should be on the front lines with their community ecosystem, and what that relationship should look like between community leaders and researchers.

While we often hear about the need for diversity in terms of race and ethnicity, it's equally important to consider a broader global perspective. Rare diseases affect people all over the world, and what works for one person might not work for another. By involving researchers from different countries, we can learn from each other and find better treatments that work for everyone, no matter where they live.

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. By actively working together and engaging with our diverse global community, we aim 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.

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The Rare Disease Diversity Coalition (RDDC) serves as a fantastic resource to the rare disease community – bringing together rare disease experts, patient organizations, health and diversity advocates, and industry leaders with a deep knowledge of the medical, industry, regulatory, and cultural challenges facing people of color with rare disease.

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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!

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For more information about the importance of engaging a diverse global community in clinical research and trials, you can listen to these podcasts from Global Genes in addition to watching other sessions from the 2023 Global Genes RARE Health Equity Forum:

• Turning Words into Action: Equity, Diversity, and Inclusion in Rare Disease

• Addressing the Barriers to Patient Participation in Clinical Trials

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Wg Williams, Elijah's dad, shares their story.

"At only 15 months old, my son started undergoing lots of medical testing and treatments associated with his Shwachman-Diamond syndrome (SDS). He was only about 28 months old when his medical treatment-related anxiety started to become concerning. This became a separate new issue of his negative well-being. His anxiety would start to trigger in the parking lot of the doctor's office and only heightened from there. When he heard his named called in the waiting room he would start to cry in fear.

At the time I was looking in the marketplace for the ideal childhood product that would inform, distract and reward my son in his participation in these procedures. I was looking for something in which the sugar-coat wasn’t so thick, and the distraction did not suggest that pain wouldn’t exist. I found no such children's product.

I knew from having 11 nieces and nephews that regardless of what adults told children, they created fictitious monsters for their fears and imagery heroes overcome them. I wanted my son to see himself as a brave hero overcoming his reasonable fears associated with the pain and uncharted aspects of his medical tests and treatments. I then started to think that I could create such a tool myself. Being a big sci-fi fan and amateur writer, I remembered a quote I had learned; “Any sufficiently advanced technology is indistinguishable from magic”. This was from Arthur C. Clarke's “Profiles of the Future: An Inquiry into the Limits of the Possible”, a non-fiction book.

I was thinking of a story that would be on a kid’s level of understanding and within their childhood interests. This would be a fun fantasy tale to grasp a child's imagination but also inspire bravery. I wanted an origin type story with cute magical animals that kids would adore. I wanted to include how these kids, who are actual heroes, could become their own hero kid in the making. I wanted a story easily understood by very young kids but still interesting and exciting to kids 10 years old. Children like him will always be heroes and modern medicine is truly magical. This story although fantasy, would also have to be an accurate kid’s self-help instruction manual for these medical procedures. The end result was this children’s picture book, Hero Kids in the Making!"

About Wg Williams' children's picture book:

Finally, a tool that prepares children for medical procedures in a fun way! This colorful storybook was especially created to help reduce childhood fears in their inevitable encounter with medical devices. "Hero Kids in the Making" is a children's picture book that redirects the imagination of a pediatric patient from a fearful perspective and towards a hero making tale that inspires bravery.

This fun rhyming story turns medical procedures into cute, magical creatures. Instruments such as stethoscopes, syringes and imaging equipment are transformed into these magical animals, now in disguise. It's a fantasy hero making version of what the child will really experience during a doctor's or hospital visit. When a child familiar with this fantasy tale experiences medical procedures, they instantly become a hero character of the story themselves.

The Coloring Book collaboration:

When the SDS Alliance heard bout the book, the team fell in love with the story immediately. We started to think about how we could make it more accessible (easy to download and print) and more interactive for the kids. This is how the coloring book idea came to be. And luckily for the community, a 9-your-old child with SDS volunteered to create illustrations. The Hero Kids in the Making COLORING BOOK is now available on our kids' corner page. Check it out, today.

To request printed copies and/or stickers, email us at connect@SDSAlliance.org

Gabe passed away from AML following an unsuccessful stem cell transplantation, surrounded by his family. He leaves behind a sister, his parents, and a loving community of extended family and friends.

His parents and community are so proud of all he has been able to achieve in his life. He graduated high school despite being sick, with a GPA of 4.7 and an Eagle Scout.

His mom shares:

If you would like to support his family, please consider donating to the GoFundMe page the family has set up at the start of his transplant journey: https://www.gofundme.com/f/35s8s2-team-gabe

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 World Cancer Day and National Cancer Prevention Month: A Vital Effort for the Shwachman-Diamond Syndrome Community

This past week, on February 4, communities from all over the world came together to raise awareness about cancer prevention, cancer care, and the barriers that prevent equitable access to these life-saving measures on World Cancer Day. In fact, the whole month of February marks National Cancer Prevention Month in the United States, a time dedicated to raising awareness about cancer prevention strategies and advocating for healthier lifestyles.

In a world where cancer affects millions of lives each year, this month serves as a reminder of the importance of proactive measures in reducing cancer risk. For communities like ours affected by Shwachman-Diamond Syndrome, where the risk of developing cancer, especially myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML), is significantly elevated, this awareness becomes even more critical. Studies have shown that approximately one in three individuals with SDS will develop MDS or AML by the age of 30, underscoring the urgent need for effective prevention strategies within this community.

Below is a video by Osmosis that explains what blood cancer (leukemia) is. Although AML is the biggest concern in SDS, it is important to recognize that other types of blood cancers, and several types of other cancers have been reported in SDS patients. See for example this article from France by Dr. Jean Donadieu., which we will summarize in an upcoming issue.

World Cancer Day and National Cancer Prevention Month provide an opportune moment to highlight the significance of early detection, healthy lifestyle choices, and regular screenings in reducing cancer risk, particularly for individuals with SDS. While the genetic predisposition to leukemia in SDS cannot be altered (yet!), lifestyle factors such as maintaining a balanced diet, exercising regularly, smoking cessation, and avoiding exposure to environmental toxins can play a crucial role in mitigating overall cancer risk.

Moreover, regular medical surveillance and screenings tailored to the specific needs of SDS patients are paramount. Routine blood tests, bone marrow evaluations, and genetic counseling can aid in the early detection of any abnormalities or pre-cancerous conditions, allowing for timely intervention and treatment. Although advancements in medical research have led to the development of targeted therapies and treatment protocols tailored to the unique challenges presented by many cancers, research is still ongoing about how we can better treat MDS, AML, and other cancers in individuals with SDS.

As we observe World Cancer Day and National Cancer Prevention Month, let us reaffirm our commitment to promoting health, advocating for access to comprehensive healthcare services, and supporting ongoing research efforts aimed at better understanding and addressing the complexities of cancer risk within the SDS community. By fostering a culture of prevention, education, empowerment, and active participation in all facets of research and therapy development, we can move towards a future where the burden of cancer is significantly reduced, and individuals with rare disorders like SDS can live longer, healthier lives free from the fear of cancer.

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Why is research on cancer prevention so critical to progress against cancer? This resource from the National Cancer Institute provides an overview of opportunities and challenges in cancer prevention research: http://bit.ly/31oGH8O

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The Centers for Disease Control and Prevention is working to prevent cancer through a number of innovative programs. Here’s how they are achieving progress against the disease: http://bit.ly/2SlvVvR

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For more information about World Cancer Day and National Cancer Prevention Month, you can visit these websites:

• World Cancer Day (Materials available in multiple languages!)

• American Association for Cancer Research: National Cancer Prevention Month

• Cancer Prevention Quiz

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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!

The Science Snapshot this week contains content modified from a blog post published by the Chan Zuckerburg Initiative (CZI) and written by Samantha Yammine.

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Revealing the Mysteries of Human Cells

In a previous Science Snapshot on Understanding the Role of Genes, we briefly reviewed what cells are, the role of genes as instructions for these cells, and the difference between germline/hereditary variants (i.e., mutations) and somatic/acquired variants.

In this week’s Science Snapshot, we will be highlighting an interactive and informative blog post published by the Chan Zuckerburg Initiative (CZI) and written by Samantha Yammine, which answered some of the frequently asked questions about the cells that make up our bodies.

How many cells are there in the human body?

The current best estimate is that the average body contains about 37.2 trillion human cells. There are more cells making up the human body than the number of seconds in one million years. And about 372 times as many cells making just one body than there are stars in our home galaxy, the Milky Way. And that’s without factoring in the trillions of single-celled microbes living throughout the human body in symbiosis (i.e., these microbes positively benefit the function of the human body just as our bodies support their survival).

These trillions of cells are the basic functional unit of our biology, coming together to form the different organ systems in our body. Cells come in many forms and functions — from elongated cardiomyocytes that help the heart contract, to the tree-shaped neurons that transmit electrochemical messages throughout the brain, and biconcave, disc-shaped cells carrying iron throughout our blood. Researchers are working to map all of these different cells in our body to better understand health and disease.

Image credit: 10 Questions Revealing the Mysteries of Human Cells

How big is a cell?

Human cells come in a range of sizes, though most are too small to be seen with the naked eye. The main exception to that is the ovum, or egg cell, which is among the largest cells in the body at about 0.1 millimeters (or 100 micrometers) across. Rival to the unusually large size of the ovum are motor neurons emanating from the spinal cord down to the biggest toe. These are about 100 times thinner in diameter than the ovum, but have a single projection running the length of the leg, reaching up to one meter long.

Most other human cells average about 10-100 micrometers in diameter. To picture that scale, imagine a single grain of salt cut into five pieces. Each of those pieces would be about the size of the average human cell — no longer visible without magnification, and so small that about 635 of these cells could fit across the diameter of a penny.

The size and shape of a cell is closely tied to its function, and can change over time. The growth and division of cells are very carefully regulated to maintain a healthy state.

Does every single cell in my body have the same DNA?

For the most part, yes, every cell in the body has roughly the same set of DNA. That’s because all cells in the body originate from the fertilized egg, created through many, many rounds of cell division. Each time the cell divides, it makes a copy of its genetic material so there is enough to be passed on to the new cell.

While there are many “proofreading” steps to reduce errors in the process of duplicating DNA, there are approximately 120,000 copying mistakes across the 6 billion bases in the genetic code every time a cell divides. While most of these changes do not amount to any significant changes in the genetic code, they can accumulate as cells in the body continue to divide over our lifetime.

While every cell in a person’s body has nearly the same set of DNA, cells become different depending on the subset of the DNA being used. It’s similar to how an orchestra works: all of the instruments are there, but not all of them are getting played at once, and depending on the timing and combination of instruments you can get completely different music from the same set of instruments. While every cell has the full set of DNA, as a cell develops and specializes it uncoils the parts of DNA it needs to use and coils up the parts that are less relevant to its functions. That’s how a muscle cell ends up different from a skin cell, even though they have the same set of genetic instructions.

Researchers want to learn more about how differences in people’s DNA, environments, and lifestyles impact their health to formulate more precise treatments and prevention strategies. CZI has partnered with the US’ four historically Black medical colleges to further support their cutting-edge scientific research in this field to accelerate precision health for all.

Image credit: 10 Questions Revealing the Mysteries of Human Cells

How many different types of cells are there in the human body?

Historically the answer has been that there are about 200 different types of cells in the human body, but new technology in the last decade has uncovered many more than that, totalling a couple thousand.

For example, we’ve known for over a century that there are four main types of cells in the brain: message-conducting neurons, star-shaped support cells called astrocytes, cells that insulate neuronal connections called oligodendrocytes, and specialized immune cells that survey and respond to changes in the brain called microglia. From the first glimpses of these cells through the earliest of microscopes it became clear there are many subcategories of each of these cell types.

But it’s taken advances of imaging technology and molecular biology to fully begin to realize just how varied cells can be. For example, the Tabula Sapiens is a project by the Chan Zuckerberg Biohub San Francisco and CZI to map cells of the human body using molecular data. They have already characterized over 400 different cell types using molecular data from studying 500,000 cells from 24 different tissues and organs. The data in these comprehensive cell atlases put a spotlight on the subtle differences between cells that are key to maintaining health, and help us better detect the early changes that lead to disease.

How does understanding the cell’s response to disease allow us to develop new therapies?

Diseases result from a change in our body’s function, right down to the level of our cells. By studying which cells are affected in a disease and what changes are happening to everyday cell processes, researchers will be better poised to treat the root cause of a disease. That’s because understanding more about the biology of a disease can enable researchers to identify new targets for medications, better understand disease progression, make more personalized predictions of how someone may respond to a treatment, and develop preventative measures for disease.

For example, rare diseases often involve specific genetic mutations or changes to how genes and proteins are regulated, which point to the role they play in our cells. Through the CZI Patient-Partnered Collaborations for Rare Neurodegenerative Disease and Single-Cell Analysis of Rare Inflammatory Pediatric Disease, researchers and patient organizations are partnering to accelerate our understanding of some of the more than 7,000 rare diseases affecting more than 300 million people worldwide. This work not only advances us towards new treatments for these diseases, but gives us a better understanding of basic cellular processes that are important to treating common diseases, too.

Image credit: 10 Questions Revealing the Mysteries of Human Cells

What are some unsolved problems in cell biology?

Each of the 37.2 trillion cells in the human body is like a whole city of biological activity. Each cell is complex with many parts interacting within an ever-changing environment. There is so much we still don’t know about how individual cells in our bodies change over time and how they interact as systems in our tissues and organs.

While new technology is giving researchers a front-row seat to that activity, collaboration and open sharing of data and tools is key to transforming this new information into scientific breakthroughs.

CZI is building open source software tools to accelerate science, funding important research and launching institutes to do research that can’t be done in conventional environments.

For the next 10 years, our goal (of the CZI and SDS Alliance!) is to understand the biggest biological mystery about the human body — the cell. A foundational understanding of how they work will lead to discoveries that will change medicine in the decades that follow.

Image credit: 10 Questions Revealing the Mysteries of Human Cells

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For more information about what are some of the important cellular components, like ribosomes and mitochondria, you can review this previously published Science Snapshot or watch this YouTube video.

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10 Questions Revealing the Mysteries of Human Cells.

Chan-Zuckerburg Initiative

Blog Post Written by Samantha Yammine

July 27, 2023

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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!

Rare Disease Moonshot: Europe’s Public-Private Coalition to Erase the Rare Disease “White Spots”

In their latest issue, the DIA Global Forum publication highlights policy advances for rare disease research at the European level. Read the full article here.

The Patient Voice

YOUR VOICE MATTERS! Make it count! Turn hope into action an join us!

The patient voice -- or more specifically, patient-reported data -- is crucial for drug development and regulatory approval by the FDA and EMAE for several reasons. Including patient perspectives and experiences in the evaluation process enhances the overall understanding of a drug's effectiveness and safety.

• Patient-Centric Focus: Incorporating patient-reported outcomes (PROs) ensures that drug development is centered around patients' experiences and the impact of the condition on their daily lives. This patient-centric focus aligns with the goal of developing treatments that genuinely address patients' needs and improve their quality of life.

• Measuring Treatment Benefits: Patient-reported data provides direct insight into the benefits of a treatment from the patient's perspective. This information is particularly valuable in assessing the drug's impact on symptoms, functioning, and overall well-being, which may not be fully captured by traditional clinical measures alone.

• Endpoint Selection: Patient-reported outcomes can help inform the selection of meaningful and relevant endpoints for clinical trials. By including endpoints that matter to patients, researchers can design studies that better reflect the real-world impact of a drug, making the results more applicable to patients' experiences.

• Clinical Trial Design and Recruitment: Patient-reported data is essential in the design of clinical trials, helping researchers determine the appropriate study population, design patient-friendly protocols, and enhance recruitment strategies. This contributes to the overall success and efficiency of clinical trials.

• Regulatory Requirements: Regulatory agencies, such as the FDA, increasingly recognize the importance of patient-reported data in evaluating drug safety and efficacy. In many cases, the FDA requires the inclusion of PROs in clinical trial protocols, and positive patient-reported outcomes can support a drug's approval by demonstrating its meaningful impact on patients' lives.

• Labeling and Communication: Patient-reported data can influence the content of drug labels, ensuring that important information about the drug's benefits and risks is communicated clearly to healthcare providers and patients. This transparency aids in informed decision-making and appropriate use of the medication.

• Post-Marketing Surveillance: Patient-reported data continues to be valuable after a drug is on the market. Monitoring patient experiences and outcomes post-approval helps identify any previously unrecognized side effects, assess long-term benefits, and guide further recommendations for use.

• Health Economics and Market Access: Patient-reported outcomes contribute to health economic assessments and market access strategies. Demonstrating the positive impact of a drug on patients' lives can influence reimbursement decisions and market access, making the drug more widely available to those who need it.

YOUR VOICE MATTERS! Make it count! Turn hope into action an join us!

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 Study Investigates Patient Preferences in the Development of Cancer Screening Technologies

FasterCures, a center of the Milken Institute, works to build a system that is effective, efficient, and patient-centered with focus areas in accelerating innovation, building nonprofit capacity, improving the research and development environment, and strengthening global health.

Additionally, FasterCures works to embed the experiences and preferences of patients across the biomedical ecosystem to address patient needs and improve outcomes.

With this in mind, last fall, FasterCures published a study, The Impact of Insight: Patient Preferences in Novel Screening Technologies for Cancer, exploring patient preferences in cancer screening and early interventions with the goal of informing current patient care guidelines and the development of future cancer screening technologies and interventions.

As a side note, our CEO Dr. Eszter Hars, had the privilege to participate in the latest cohort of the Milken Institute FasterCures LeadersLink Program and recently completed a capstone project centered around patient data resources. More about this project coming soon.

What This Study Found

As screening technologies advance and detect cancer earlier, it is imperative that the development process for early intervention modalities includes patient insights. The incorporation of patient preferences into the development and advancement of early intervention technologies and treatments are equally important.

Based on their extensive research and engagement with stakeholders, this study identified the following patient preferences in cancer screening, early detection, and interventions:

Image credit: The Impact of Insight: Patient Preferences in Novel Screening Technologies for Cancer

This study also identified several key issues with the development of new cancer screening and early intervention modalities including:

• Unawareness of Individual Risk of Cancer and Recommended Screenings

• Lack of Diversity in Research

• Limited Access to Screening Tests

• Lack of Patient Engagement in the Development of Medical Products

• Limited Capabilities of Current Screening Tests

To address these issues, the authors recommended multiple calls to action, encouraging patient insights to be actionably embedded throughout the research, development, and implementation of cancer screening and early intervention tools. Some of these calls to action include:

• Invest in research to better understand the biology of cancer,

• Stratify cancer screening recommendations based on genetic risk, lifestyle, and behavior,

• Increase the use of genetic testing to create personalized screening plans for individuals with a family history of cancer,

• Ensure clinical trials for new technologies include participants from diverse communities,

• Invest in accessible screening technologies and/or initial, self-administered screenings in the home,

• Continue to engage patients in the development of new screening technologies and early interventions for cancer treatment, and

• Prioritize the development of screening technologies for lethal cancers and cancers without current screenings.

What Does This Mean for You?

While we recognize there is more complexity to SDS than its cancer risk and developing and implementing appropriate cancer screening recommendations, this study serves as a great example of the unique needs and preferences that exist amongst different disease communities. SDS Alliance is committed to not only responding to these authors’ calls to action, but also to exploring and incorporating the needs and preferences of the SDS community when establishing our research priorities and designing clinical trials. Together, we can improve outcomes and find a cure for SDS!

Make your voice heard: Engage, share your story, and get involved in advocacy.

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The Science Snapshot this week contains content modified from materials distributed by the Milken Institute and FasterCures.

The Impact of Insight: Patient Preferences in Novel Screening Technologies for Cancer

Milken Institute: FasterCures

In Partnership With: The Rising Tide Foundation

September 21, 2023

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!

The Importance of Data Collection and Data Privacy in Rare Disease Research

Research in rare disease is comparable to putting together a puzzle with each piece of that puzzle serving as a small piece of information about a condition, or in our case, Shwachman-Diamond Syndrome (SDS). To understand the whole picture of SDS, develop treatments, and discover a cure, we need to gather all of the puzzle pieces. This gathering of information is what we call data collection. In the context of rare disease research, because of the scarcity of individuals affected, each piece of information or data point (i.e., every piece of the puzzle) becomes very valuable. And when we put the puzzle pieces together (a process known as data aggregation), it becomes easier to see the complete picture, or gain a better understanding of the disease landscape. This process of putting the puzzle together is crucial for advancing research in rare disease because with more information, scientists and researchers can learn more about the causes, symptoms, and potential treatments for these rare conditions.

Image credit: https://www.zamplo.org/rare-disease

However, the significance lies not only in the collection and synthesis of data but also in the collaborative sharing of this information and findings. If only one person had some puzzle pieces and kept them to themselves, we wouldn't be able to see the whole picture. Similarly, when researchers share their findings and data with each other, it helps everyone in the scientific community work together to solve the puzzle of rare diseases.

In rare disease research, while collaboration is the key to advancing research in rare disease, data privacy and the protection of participants and their data is equally as important. To make a simple analogy, it's like having a lock on your diary or a secret box where you keep your special things. In the world of data collection, data privacy entails the responsible and secure handling of information. It is imperative to balance the necessity of sharing critical information with the imperative to protect individuals' private data. This ensures that progress in understanding and treating rare diseases is achieved while upholding the ethical responsibility researchers have to respect patient privacy.

As we begin the new year, SDS Alliance wants to renew our commitment to the SDS community to support, fund, and perform research that is collaborative and productive, while also protecting the privacy of our patient community. We look forward to working together to assemble the puzzle that is SDS in 2024!

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For more information about data collection and data privacy in rare disease research, you can view this presentation by Sanath Kumar Ramesh, hosted by the Critical Path Institute’s Rare Disease Cures Accelerator-Data and Analytics Platform (RDCA-DAP), recently.

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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!

Decoding Ribosomes and Exploring Ribosomopathies through the Lens of Shwachman-Diamond Syndrome

Within the complex machinery of our cells, ribosomes play a crucial role in crafting proteins – the building blocks essential for life and most of our bodily functions. In this blog post, we'll break down what ribosomes are and explore ribosomopathies, using Shwachman Diamond Syndrome (SDS), as an example of how issues with ribosomes can impact health.

The Role of Ribosomes

Ribosomes are cellular structures responsible for translating the genetic instructions encoded in our DNA into proteins. These microscopic protein factories assemble amino acids in a specific sequence to form proteins that carry out diverse tasks within our cells. Proteins are vital for cell structure, function, and regulation, making ribosomes pivotal in maintaining our overall health. (With how big of a role ribosomes play, it is not surprising that many organ systems in the body are affected if the process of protein production is disrupted!)

The creative video below explains protein synthesis and the important role ribosomes play in this process!

Understanding Ribosomopathies in the Setting of Shwachman-Diamond Syndrome

Ribosomopathies are a group of rare genetic disorders characterized by abnormalities in the structure or function of ribosomes. These disruptions can lead to errors in protein production (i.e., synthesis), resulting in either the formation of defective proteins or a shortage of functional ones. The consequences of ribosomopathies can manifest in various health issues, affecting different organs and systems in the body.

Another way to think about protein production is by comparing ribosomes to a pair of hands that use individual Legos (i.e., amino acids) to build large Lego towers (i.e., proteins). The order of amino acids, or Lego blocks, is specified by the genetic code in our DNA. In SDS, a genetic change in a patient’s DNA (i.e., a mutation) reduces the number of functional ribosomes, which in turn reduces the cells' ability to make enough protein overall. It’s like not having enough hands to meet the protein demands of the body.

In SDS, the dysfunction of ribosomes impacts the bone marrow's ability to produce healthy blood cells. This can lead to conditions like anemia, where there's a deficiency of healthy red blood cells, affecting oxygen transport, resulting in fatigue and impacting overall well-being.

The Path Forward

SDS Alliance, researchers, and physicians are actively engaged in unraveling the complexities of ribosomopathies. For example, Drs. Venturi and Montanaro described How Altered Ribosome Production Can Cause or Contribute to Human Disease in their 2020 article published in Cells, which provides an overview of other ribosomopathies such as Diamond-Blackfan anemia and Treacher Collins syndrome. Additionally, Dr. Alan Warren's laboratory has published several manuscripts, Molecular basis of the human ribosomopathy Shwachman-Diamond syndrome (2018) and Defective ribosome assembly in Shwachman-Diamond syndrome (2011), which provide more information about the role of ribosomes in SDS.

By studying conditions like SDS and other ribosomopathies, scientists aim to understand the molecular intricacies that lead to disruptions in ribosomal function. This deeper understanding holds the key to developing targeted therapies and interventions for individuals affected by these rare disorders, offering a brighter outlook for those facing the challenges of ribosomopathies.

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To learn more about the medical aspects of and science behind SDS, visit our What is SDS? and Science webpages.

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