In this issue: SDS Alliance celebrated and raises awareness about Shwachman-Diamond Syndrome and inspires action in the community Welcome to our timely updates on all things SDS, Science, and Advocacy. We bring you a digest of recent scientific publications, conferences, and other newsworthy content - all relevant to SDS - with links to more details and learning opportunities. Are you interested in anything specific? Did we miss something? Let us know. Email genetics@SDSAlliance.org or message us on Facebook! This is all for you! What is Shwachman-Diamond Syndrome Global SDS Awareness Day and Action Week? Global SDS Awareness Day and Action Week  is about coming together and raising awareness as a united global patient community. ​ In 2020, the SDS Alliance reached out to all the international SDS patient organizations to discuss the idea of creating an annual Global SDS Awareness event, proposing a time in spring or fall to avoid the busy winter holiday and summer vacation seasons. Our colleagues at SDS UK proposed late April as the time to coincide with Dr. Shwachman's birthday. All organizations that responded - including SDS UK, SDS Netherlands, and SDS Foundation (US) - supported this concept and timing, and so Global SDS Awareness Week was born. ​​ ​Over the years, the event has not reached its full potential, so we set out to reconsider the date. We polled the international patient community for a new date/frame preference. You voted and we listened! ​Based on your feedback, the new date(s) are:   Global SDS Awareness Day is November 7th   and leading up to it, ​ Global SDS ACTION Week is November 1-7th Take Action to Make an Impact! Here is a list of simple actions you can take, one or two a day during Global SDS Action Week - or anytime throughout the year. Click on the list to download a PDF  with clickable links. How will you take action this year? New! Share a vocal video! We partnered with Vocal Video to bring you a super easy way to share your voice by answering a few simple questions. See an example (Eszter's video) on the SDS Alliance webpage for Awareness Week . Click here or below to share your voice, today! We will use your videos to raise awareness about SDS and to inform our programs to best support your needs! Why was November chosen for SDS Awareness?   Dr. Shwachman was a prominent gastroenterologist in Boston in the 1960s and developed deep expertise in caring for Cystic Fibrosis (CF) patients and "atypical" CF patients. This was before SDS was recognized as a distinct disorder, and many patients were categorized as "atypical CF."  Drs. Shwachman and Diamond , as well as Dr. Bodian , were instrumental in defining Shwachman-Diamond Syndrome. A landmark publication in the journal Pediatrics in 1964, entitled " The Syndrome of Pancreatic Insufficiency and Bone Marrow Dysfunction " was published by Drs. Shwachman and Diamond in November 1964. It is due to this publication that the disease received its name, "Shwachman-Diamond Syndrome". About 40 years later, Dr. Johanna Rommens and her team at SickKids in Toronto, Canada, identified the main gene responsible for SDS. The gene (and corresponding protein) was named SBDS for S hwachman- B odian- D iamond S yndrome to acknowledge Dr. Bodian's contribution to the field. Coincidentally, the SBDS gene happens to be located on section 11 or Chromosome 7, giving a nod to the date of 11.7 or November 7. ​ New SDS Awareness T-shirt Designs Now Live!   Click on the design to order.  Multiple colors and styles are available, including t-shirts, hoodies, and tank tops. International shipping is available. If you would like to have them printed locally in your country or community, email us at connect@sdsalliance.org and we will be happy to share the design file! ​ Why participate in SDS Awareness Day and Action Week? ​ It is our hope that more and more organizations and families will participate over time so that this campaign can grow and reach more families, medical providers, and researchers. We have reached out to all international SDS patient groups to invite them. ​ Raising awareness can save lives. Any diagnosis made sooner lessens the burden and suffering of the diagnostic odyssey, and life-saving interventions can begin sooner. The SDS community can grow to support more targeted research, accelerating the pace toward therapies and cures. ​ SDS Story Series Huge thanks to all the SDS families from around the world for sharing their stories!   The stories are available on the SDS Alliance social media channels: SDS Alliance Website blog (Patient Stories) SDS Alliance Facebook page The Role of SDS Alliance We at the   SDS Alliance  are not only passionate to raise awareness about SDS, patient's unmet needs, and our drive for progress, but we are equally if not more passionate about creating opportunities for YOU to make a difference. The Action Checklist on top of this post is an easy way for you to get started and take action that matters. Together, we can move mountains. We created many resources to set you up for success. Check out the media section of our website for free downloads. Why Community Matters Being part of a community provides emotional support and access to the latest research and treatment options. SDS Alliance advocates for awareness, research funding, and educational resources that can greatly enhance the quality of life for those affected by SDS. Conclusion Shwachman-Diamond Syndrome is a complex genetic disorder that requires coordinate care, caring community support, and strategic investment into research and research infrastructure to de-risk therapy development. Organizations like Shwachman-Diamond Syndrome Alliance (SDS Alliance) play a crucial role in providing support and resources for those affected and the SDS community at large. Join us and raise awareness to help others learn about this important condition. For more information, visit   SDS Alliance  and join a community dedicated to improving the lives of those impacted by Shwachman-Diamond Syndrome. Do you enjoy the SDS & Science Snapshots? You can Sign up by using the button on the top right of this post :

In this issue: The SDS Alliance team is energized and ready for Global SDS Awareness Day and Action Week! A recap of the annual CZI Science in Society Meeting. Welcome to our timely updates on all things SDS, Science, and Advocacy. We bring you a digest of recent scientific publications, conferences, and other newsworthy content - all relevant to SDS - with links to more details and learning opportunities. Are you interested in anything specific? Did we miss something? Let us know. Email genetics@SDSAlliance.org or message us on Facebook! This is all for you! SDS Alliance is Energized by the Annual CZI Science in Society Meeting With yesterday’s launch of Global Shwachman-Diamond Syndrome (SDS) Awareness Day and Action Week (1-7 November) , our team at SDS Alliance is reflecting on our recent experience at the invitation-only Annual Science in Society (SiS) Meeting hosted by the Chan Zuckerberg Initiative (CZI) which brought together the CZI Rare As One (RAO)  network, a passionate community of rare disease patients and caregivers, patient advocacy group leaders, scientists, clinicians, and policymakers, committed to advancing rare disease research and improving patient outcomes. The SDS Alliance was Awarded a transformational Chan Zuckerberg Initiative “Rare As One” Grant in 2021, as part of cycle 2. The first full meeting day (16 October 2024) themed, “Accelerating Rare Disease Diagnosis,” was focused on shortening the diagnostic journey that many families face. Currently, it can take six years or more for patients with rare diseases to receive an accurate diagnosis . Experts and leaders from across the rare disease community challenged each other to envision cutting this time to just six weeks within the next six years. Discussions included emerging tools like artificial intelligence (AI) that could support real-time diagnostics, ways to better understand variants of uncertain significance, and policies to make diagnostic resources widely accessible. For the SDS Alliance team, attending this meeting was energizing, reaffirming the importance of equitable diagnostic access and showing promise for a future where SDS patients may face fewer hurdles on their diagnostic journeys. The second meeting day (17 October 2024), centered on “Data Integration for Disease Characterization” and “Impact,” brought attention to the incredible potential of patient data to propel rare disease research forward. Speakers presented innovative registries and platforms for collecting data that can characterize diseases in greater detail and support the development of new treatments. A big focus was also on making data gathering accessible and patient-centered, envisioning technologies like wearables to track health in real-time. This session was particularly insightful for the SDS Alliance team in light of our recent launch of the SDS Global Patient Survey and Collaboration Program: SDS-GPS ( learn more about the GPS Program and how to make your voice count here! ). Finally, leaders from patient-driven organizations shared successes and discussed novel funding models to advance research, offering a roadmap for how patient communities, like those affected by SDS, can contribute to and benefit from advancements in rare disease research and treatment development.  Not only did the CZI SiS meeting provide the opportunity for SDS Alliance team members  Ashley Ferreira (pictured on the right below) and myself (Ashley Thompson, as seen on the left) to meet in person for the first time, but it also underscored that meaningful progress for advancing diagnostics and therapeutics for the SDS community is within reach, giving SDS Alliance new ideas and a renewed sense of purpose in our advocacy and research efforts. This was the first CZI SiS meeting Ashley Ferreira had the opportunity to attend in-person. She was kind enough to write up and share her thoughts and reflections about attending this meeting and engaging with the RAO network below. Attending the 2024 CZI SiS Meeting was an inspiring opportunity that deepened my understanding of the intersection of AI, healthcare, and research. The atmosphere was electric, filled with innovators and thought leaders passionate about harnessing technology for the benefit of our rare disease communities. There were various sessions that offered valuable insights into how AI is transforming the landscape of healthcare, from pre-clinical research to personalized patient care. One of the highlights was the discussion on AI-driven predictive analytics in patient care. Experts shared case studies demonstrating how machine learning models can analyze vast datasets to identify at-risk patients before issues arise, ultimately leading to better health outcomes. The emphasis on collaboration between data scientists and medical professionals underscored the importance of interdisciplinary approaches in developing effective AI tools.  Panelists also engaged in meaningful dialogue about ensuring that systems are equitable and transparent, highlighting the need for diverse datasets to advance research in rare disease communities effectively. By leveraging advanced algorithms and machine learning, researchers can now analyze vast amounts of genetic, clinical, and demographic data more efficiently than ever before. This capability allows for the identification of patterns and potential biomarkers that were previously difficult to discern, accelerating the discovery of effective treatments. Additionally, AI-powered tools facilitate the management of patient registries, enabling more accurate tracking of patient outcomes and experiences. This holistic approach not only fosters collaboration among researchers but also empowers patients and advocates to contribute to the knowledge base, ultimately driving progress in understanding and treating rare diseases. Do you enjoy the SDS & Science Snapshots? You can Sign up by using the button on the top right of this post :

In this issue: The results of the 2024 Million Steps Closer to #CureSDS Challenges are in Welcome to our timely updates on all things SDS, Science, and Advocacy. We bring you a digest of recent scientific publications, conferences, and other newsworthy content - all relevant to SDS - with links to more details and learning opportunities. Are you interested in anything specific? Did we miss something? Let us know. Email genetics@SDSAlliance.org or message us on Facebook! This is all for you! Shwachman-Diamond Syndrome community and impact with the 2024 Million Steps Closer to #CureSDS fundraiser The Event for You, Your Friends, Family, and Colleagues to Have Fun and Support Research.   The Million Steps Closer to #CureSDS annual fundraiser took place October 25-31, 2024. Anywhere (Virtual or Local if You Choose). Shwachman-Diamond Syndrome is global. ​ This year, we hosted the 5th annual "Million Steps Closer" fun-run challenge fundraiser, a virtual event every October. Participants turned hope into action and took steps to #CureSDS - we could walk, run, crawl, roll, swim, or lean back and support those who do by making a donation.  The steps (and fitness) counting challenges were managed through a free app and are optional. The Purpose: To Support Research!​​​   This fundraiser is a fun and uplifting way to join us and make a difference. As always, 100% of funds raised from the community go to SDS research and infrastructure to accelerate therapy development, following our  roadmap . By participating in this event, you are playing an integral part in driving progress! Roadmap Teams Amplify Impact! ​ Participants invite family, friends, neighbors, colleagues, or classmates to participate! Registration is free! It's easily invite others to join in your fundraising efforts! Get in the spirit for next year! Overall community goal: A million steps or more! This year, once again, we had a small but committed and dedicates community step up to the challenge. 4 teams and 17 participants took an impressive total of 1,004,878 steps together Thank you everyone who stepped up and had fun with us, while meeting critical fundraising goals for research! See you again next year! And the 2024 Challenge Winners are: Laszlo H : Most Steps taken as an individual: 94,709 steps Team Joyce : Most Steps taken as a team: 353,933 steps Team Declan : Most Funds Raised as a team: $13,864 with this fundraiser and a charity hockey game in the spring. Community and Fundraising This event is impactful for both coming together as a community that can support each other, and also as a powerful driving force for research funding. The SDS Alliance is proud to host this event every year. These themes are also carried forward in the inaugural   Global SDS Awareness Day is November 7th   and leading up to it, ​ Global SDS ACTION Week is November 1-7th campaigns. Take Action to Make an Impact! Here is a list of simple actions you can take, one or two a day during Global SDS Action Week - or anytime throughout the year. Click on the list to download a PDF  with clickable links. How will you take action this year? The Role of SDS Alliance We at the   SDS Alliance  are not only passionate to raise awareness about SDS, patient's unmet needs, and our drive for progress, but we are equally if not more passionate about creating opportunities for YOU to make a difference. Conclusion Shwachman-Diamond Syndrome is a complex genetic disorder that requires coordinate care, caring community support, and strategic investment into research and research infrastructure to de-risk therapy development. Organizations like Shwachman-Diamond Syndrome Alliance (SDS Alliance) play a crucial role in providing support and resources for those affected and the SDS community at large. Join us and raise awareness to help others learn about this important condition. For more information, visit   SDS Alliance  and join a community dedicated to improving the lives of those impacted by Shwachman-Diamond Syndrome. Do you enjoy the SDS & Science Snapshots? You can Sign up by using the button on the top right of this post :

In this issue: Advocacy Impact: Shwachman-Diamond Syndrome and the community's ideas were part of last week's kick-off meeting of FDA’s Rare Disease Innovation Hub Welcome to our timely updates on all things SDS, Science, and Advocacy. We bring you a digest of recent scientific publications, conferences, and other newsworthy content - all relevant to SDS - with links to more details and learning opportunities. Are you interested in anything specific? Did we miss something? Let us know. Email genetics@SDSAlliance.org or message us on Facebook! This is all for you! Shwachman-Diamond Syndrome Alliance (SDS Alliance) shares ideas at new FDA Rare Disease Innovation Hub kick-off Meeting. FDA leaders launch rare disease hub to increase cross-center collaboration. It was an incredible opportunity for the SDS Alliance to represent the SDS community at the FDA for the public kick-off meeting of the new Rare Disease Innovation Hub!  Advocacy with Impact. Thank you to the  Reagan-Udall Foundation for the FDA  for organizing the meeting and making it possible for many rare disease organizations and advocates to be heard. The day was filled with insights from passionate stakeholders, advocates, and members of the rare disease community. FDA officials, including the directors of CBER and CDER, launched a rare disease innovation hub at a public meeting on October 16, 2024, aiming to enhance collaboration and communication across the two centers and externally, to serve as a single point of entry to engage with FDA, and to streamline and accelerate therapy development for rare diseases. The meeting was organized by the Reagan-Udall Foundation for the FDA . The Reagan-Udall Foundation for the FDA, in collaboration with FDA’s Rare Disease Innovation Hub, hosted a public meeting on October 16, 2024. The meeting brought together rare disease patient advocates, academic researchers, regulated industry, and other key stakeholders to discuss how the recently announced Rare Disease Innovation Hub can best engage with members of the rare disease community and prioritize its work. During this public meeting, FDA sought to gather public comment in the following areas: Cross-cutting rare disease-related, scientific, regulatory, or policy issues (those not related to a particular disease or condition) that should be prioritized for consideration by the Rare Disease Innovation Hub Rare disease-specific (but not application-specific) scientific, regulatory, or policy issues that should be prioritized for consideration by the Rare Disease Innovation Hub Rare disease-related activities or initiatives currently being undertaken independently by CDER or CBER that you believe would benefit from being undertaken by the Rare Disease Innovation Hub as a joint activity Approaches that the Rare Disease Innovation Hub should follow for engagement with patients and caregiver groups, industry organizations, and scientific/academic organizations In addition to the presentations during the hybrid meeting, comments can be submitted to the docket by October 31st as described in the Federal Register Notice . The full meeting recording is now available on the meeting page and on YouTube, here: Endpoints News summarizes the event in their recent article : The hub will work across different rare diseases, the vast majority of which do not have any treatment. The FDA said it will “particularly focus on products intended for smaller populations” or for diseases in which the natural history is not well understood. The hub “will bring us the coordination between the centers that I think will really make sure that things like biomarkers are coordinated,” Marks said in his introductory remarks. He added that CDER and CBER reporting structures won’t be disrupted but there will be more collaboration. CDER Director Patrizia Cavazzoni highlighted that this meeting already demonstrates how the hub “will turbo-charge our activities across centers. We really want to listen.” At the same time, they emphasized that they are in startup mode. Dynamic, strategic, AND still looking for a director to lead the effort. “There will be differences between gene therapies and protein therapeutics and small molecules,” Marks said. “That may mean that sometimes an endpoint or policy may have to be different, but again, we’re committed to being transparent about this.” The remainder of the meeting included 41 speakers — from patient groups to industry — including Shwachman-Diamond Syndrome Alliance's President and CEO Dr. Eszter Hars , discussing everything from the rare diseases of their children to ways that the FDA can be more nimble. The agency said it received more than 200 requests to participate in the meeting. Some speakers sought improved consistencies across the FDA drug and biologic centers, citing the need to establish regular and transparent lines of communication with sponsors. Others requested a roadmap for the hub’s short and long-term goals. Comments on the docket are still open, according to the FDA. Dr. Hars highlighted the need of the SDS and many other rare disease communities to collaborate with the FDA, researchers, and other stakeholders to support the development of biomarkers and outcome measures, which could support the development of new therapies using different modalities and could accelerate the work and impact across multiple agencies. More about the Rare Disease Innovation Hub from the meeting organizers and its impact on SDS Alliance's mission "An estimated 10,000+ rare diseases affect more than 30 million people – approximately one out of every 10 people – in the United States, and about half of these people are children. While there have been important advances in treatments for rare diseases, more needs to be done. Many rare diseases lack treatment options and therefore many patients have high unmet medical needs. This requires new approaches to expedite development and approval of safe and effective drugs and biologics. The FDA sees huge potential in establishing a new model, within the FDA, to leverage cross-agency expertise and greatly enhance our inter-center connectivity to spur the development of treatments for rare diseases. To that end, the Center for Biologics Evaluation and Research (CBER) and the Center for Drug Evaluation and Research (CDER) are launching a Rare Disease Innovation Hub to advance rare disease therapy development through greater communication, collaboration, and coordination across CBER and CDER, in coordination with other Centers and Offices across FDA. Helmed by senior leadership from CBER and CDER, the Hub will work to develop and implement a comprehensive cross-center rare disease strategic agenda that takes full advantage of our current clinical and scientific expertise across both centers and is based on a shared vision and comprehensive approach to 1) align methods and approaches to rare disease programs, both during IND development, and in application review; 2) identify and enable innovative approaches in the areas of novel endpoints, biomarker development, and innovative trial designs; and 3) streamline communications with the rare disease community. The Hub will work across rare diseases but will especially focus on products intended for smaller populations or for diseases where the natural history is variable and not fully understood, as we recognize that development of therapies for these conditions can be particularly challenging." This gives us at the SDS Alliance reasons for hope and momentum to implement our strategies to no only make therapy development possible, but fast and likely. The Role of SDS Alliance Organizations like   SDS Alliance  provide vital support for individuals and families affected by Shwachman-Diamond Syndrome, in particular offering access to information on the latest research and foundational understanding of the basics of research participation. They offer resources, connect patients with medical experts and researcher, and foster a community where individuals can share experiences and information and turn hope into action, together. Why Community Matters Being part of a community provides emotional support and access to the latest research and treatment options. SDS Alliance advocates for awareness, research funding, and educational resources that can greatly enhance the quality of life for those affected by SDS. Conclusion Shwachman-Diamond Syndrome is a complex genetic disorder that requires coordinate care, caring community support, and strategic investment into research and research infrastructure to de-risk therapy development. Organizations like Shwachman-Diamond Syndrome Alliance (SDS Alliance) play a crucial role in providing support and resources for those affected and the SDS community at large. Join us and raise awareness to help others learn about this important condition. For more information, visit   SDS Alliance  and join a community dedicated to improving the lives of those impacted by Shwachman-Diamond Syndrome. Do you enjoy the SDS & Science Snapshots? You can Sign up by using the button on the top right of this post :

In this issue: Why does diversity in rare disease research matter? (¡También disponible en español!) Welcome to our timely updates on all things SDS, Science, and Advocacy. We bring you a digest of recent scientific publications, conferences, and other newsworthy content - all relevant to SDS - with links to more details and learning opportunities. Are you interested in anything specific? Did we miss something? Let us know. Email genetics@SDSAlliance.org or message us on Facebook! This is all for you! Embracing Diversity in SDS: Reflecting on Hispanic Heritage Month Every year, from September 15 to October 15, we celebrate Hispanic Heritage Month in the United States. It’s a time to recognize the histories, cultures, and contributions of Hispanic and Latino Americans. But beyond the celebration, it’s also a chance to reflect on how important it is for everyone, no matter their background, to be included in healthcare and research. At SDS Alliance, we recognize that our community is diverse , and we are committed to engaging with our global community to accelerate progress towards improved treatments and outcomes with SDS across the world. That is why we made the investment to offer the SDS-GPS program in five languages, including Spanish. Join today! Rare diseases, like Shwachman-Diamond Syndrome (SDS), affect a small number of people, which means that global efforts to involve individuals from diverse backgrounds in research and awareness are critical. Cases of SDS have been reported in individuals with Hispanic heritage, including one 14-year-old female  and a 3-year-old male . Many families from diverse backgrounds who are affected by rare diseases like SDS may not have the same access to healthcare or opportunities to participate in research as others. Language barriers, lack of resources, and cultural differences can create challenges. That’s why Hispanic Heritage Month is a perfect time to focus on ensuring that the Hispanic community is included and supported in rare disease research.  For families dealing with SDS, participating in research can help improve the understanding of this condition and lead to better treatments and care. It’s important to know that research studies need input from all backgrounds to get a complete picture of how rare diseases affect people differently. A perfect example of the importance of including individuals from diverse backgrounds in clinical research includes this case series , which is one of the first to describe the EFL1 gene, a rare gene known to cause an SDS-like condition, in multiple individuals from various diverse backgrounds including two siblings with Mexican ancestry. This is why it’s crucial to raise awareness about the importance of diversity in rare disease research, so that everyone—no matter their ethnicity—can benefit from advances in medical care. At Shwachman-Diamond Syndrome Alliance, we recognize that our community is diverse, encompassing individuals of various racial, ethnic, and cultural backgrounds from around the world, and we believe that everyone's voice deserves to be heard. Hispanic Heritage Month reminds us that every culture and community brings value to the conversation, and by actively working together and engaging with our diverse global community, SDS Alliance aims to accelerate progress toward improved treatments and outcomes for individuals with SDS across the world. Together, let's continue to champion diversity and inclusivity in clinical research, ensuring that everyone has access to equitable and effective healthcare. The website for the National Organization for Rare Diseases (NORD) is available in Spanish  and so are many of their resources! Check out the EveryLife Foundation for Rare Diseases Rare Diversity Hub  for information about current efforts to increase diversity in clinical research and learn how you can get involved! En este número: ¿Por qué es importante la diversidad en la investigación de enfermedades raras? Abrazando la diversidad en SDS: Reflexionando sobre el Mes de la Herencia Hispana Cada año, del 15 de septiembre al 15 de octubre, celebramos el Mes de la Herencia Hispana en Estados Unidos. Es un momento para reconocer las historias, culturas y contribuciones de los hispanos y latinoamericanos. Pero más allá de la celebración, también es una oportunidad para reflexionar sobre lo importante que es para todos, sin importar su origen, estar incluidos en la atención sanitaria y la investigación.   En SDS Alliance, reconocemos que nuestra comunidad es diversa  y estamos comprometidos a colaborar con nuestra comunidad global para acelerar el progreso hacia mejores tratamientos y resultados con SDS en todo el mundo. Por eso hicimos la inversión para ofrecer el programa SDS-GPS en cinco idiomas, incluido el español. ¡Únete hoy! Las enfermedades raras, como el síndrome de Shwachman-Diamond (SDS), afectan a un pequeño número de personas, lo que significa que los esfuerzos globales para involucrar a personas de diversos orígenes en la investigación y la concientización son fundamentales. Se han informado casos de SDS en personas de ascendencia hispana, incluida una niña de 14 años  y un niño de 3 años . Es posible que muchas familias de diversos orígenes que se ven afectadas por enfermedades raras como el SDS no tengan el mismo acceso a la atención médica ni las mismas oportunidades para participar en investigaciones que otras. Las barreras lingüísticas, la falta de recursos y las diferencias culturales pueden crear desafíos. Es por eso que el Mes de la Herencia Hispana es un momento perfecto para centrarse en garantizar que la comunidad hispana sea incluida y apoyada en la investigación de enfermedades raras. Para las familias que padecen SDS, participar en la investigación puede ayudar a mejorar la comprensión de esta afección y conducir a mejores tratamientos y atención. Es importante saber que los estudios de investigación necesitan aportaciones de todos los orígenes para obtener una imagen completa de cómo las enfermedades raras afectan a las personas de manera diferente. Un ejemplo perfecto de la importancia de incluir personas de diversos orígenes en la investigación clínica incluye esta serie de casos , que es una de las primeras en describir el gen EFL1, un gen raro que se sabe que causa una afección similar al SDS, en múltiples personas de diversas procedencias. orígenes que incluyen dos hermanos con ascendencia mexicana. Por eso es crucial crear conciencia sobre la importancia de la diversidad en la investigación de enfermedades raras, para que todos, sin importar su origen étnico, puedan beneficiarse de los avances en la atención médica.  En la Alianza del Síndrome de Shwachman-Diamond, reconocemos que nuestra comunidad es diversa y abarca personas de diversos orígenes raciales, étnicos y culturales de todo el mundo, y creemos que la voz de todos merece ser escuchada. El Mes de la Herencia Hispana nos recuerda que cada cultura y comunidad aporta valor a la conversación y, al trabajar juntos e interactuar activamente con nuestra diversa comunidad global, la SDS Alliance tiene como objetivo acelerar el progreso hacia mejores tratamientos y resultados para las personas con SDS en todo el mundo. Juntos, sigamos defendiendo la diversidad y la inclusión en la investigación clínica, garantizando que todos tengan acceso a una atención sanitaria equitativa y eficaz. ¡El sitio web de la Organización Nacional de Enfermedades Raras (NORD)  está disponible en español y también lo están muchos de sus recursos! Consulte el Centro de Diversidad Rara de la Fundación EveryLife  para Enfermedades Raras para obtener información sobre los esfuerzos actuales para aumentar la diversidad en la investigación clínica y aprenda cómo puede participar. Do you enjoy the SDS & Science Snapshots? You can Sign up by using the button on the top right of this post :

In this issue: Understanding genetic variants and what these DNA changes mean! Welcome to our timely updates on all things SDS, Science, and Advocacy. We bring you a digest of recent scientific publications, conferences, and other newsworthy content - all relevant to SDS - with links to more details and learning opportunities. Are you interested in anything specific? Did we miss something? Let us know. Email genetics@SDSAlliance.org or message us on Facebook! This is all for you! How To Interpret Genetic Variants and Their Role in Health In this week’s SDS & Science Snapshot, we are highlight some of the important work of GenomeConnect . GenomeConnect is part of the Clinical Genome Resource (ClinGen), an NIH funded research project. GenomeConnect is a registry that helps you share your genetic and health information. Sharing this information will help increase our understanding of how genes affect health. A team member from GenomeConnect will be presenting at the upcoming SDS Alliance Global Patient Advocacy and Partnering Summit (POPS) hosted virtually on Sunday, October 20 at 1 PM EDT. Register and see the details on the SDS-POPS event page , here! In GenomeConnect’s recent newsletter , they published an infographic summarizing the process of detecting a genetic change (or “variant”) with genetic testing and then determining if the detected variant(s) impact health and disease-risk through a process known as “variant classification.” We have discussed the role of inherited (or germline) genetic variants  in previous SDS & Science Snapshots. The infographic and discussion below provides additional information about the variant classification process. During the variant interpretation process, experts ask important questions like: Have scientists studied this variant in a lab to see what it does? Was the variant inherited from a parent? Are there similar variants that have been studied before? Is this variant common in the general population? Has it been found in anyone who shows symptoms? And finally, what does the variant do to the protein it affects? Everyone has variants in their genome – some impact health, while others do not. These genetic variants are part of the differences that make us all unique and there are different levels of classification for variants detected with genetic testing:  Benign  and likely benign (B/LB) variants are not (or are likely not) related to disease and are not expected to cause health problems. Some genetic testing laboratories report B/LB variants, while others do not since they are genetic changes that are not anticipated to impact your health.  A genetic change classified as a variant of uncertain significance (VUS)  is more of gray area — experts aren’t sure yet if it’s related to disease or not. Pathogenic and  likely pathogenic   (P/LP) variants are definitively (or likely) related to disease and health. Genetic testing results are often considered “positive” if one or more P/LP variants are detected. Over time, as scientists do more research and more people undergo genetic testing, variants, especially VUSs, may be reclassified if new information becomes available. If you have had genetic testing, GenomeConnect encourages you to periodically check-in with the healthcare provider who ordered your genetic testing (or the genetic testing laboratory directly) to see if there have been any updates to the classification of a variant (or variants) previously detected that may impact your care. Plus, when you participate in the SDS-GPS program , you can opt-in to receive updates if we learn about changes to classifications . Watch the YouTube video below published by GenomeConnect to learn more about the variant classification process and explore GenomeConnect’s YouTube pl aylist  for more videos about genetics, genetic testing, how to read a genetic report, and more! For more information regarding the genetics of SDS specifically, you can watch this video  published by SDS Alliance. Do you enjoy the SDS & Science Snapshots? You can Sign up by using the button on the top right of this post :

In this issue: New case report - successful treatment of breast cancer in a patient with SDS! Welcome to our timely updates on all things SDS, Science, and Advocacy. We bring you a digest of recent scientific publications, conferences, and other newsworthy content - all relevant to SDS - with links to more details and learning opportunities. Are you interested in anything specific? Did we miss something? Let us know. Email genetics@SDSAlliance.org or message us on Facebook! This is all for you! New Case Report: Managing Solid Tumors in SDS - Challenges and Treatment Strategies As frequently discussed in the Shwachman-Diamond Syndrome (SDS) community, some individuals with SDS develop serious blood cancers, like leukemia, during their lifetime. Solid tumors, like breast cancer, are less common in individuals with SDS but can still happen. In this week’s SDS & Science Snapshot, we are highlighting a recently published article  which shares the story of an adult woman with SDS who was successfully treated for stage IV breast cancer using a combination of chemotherapy and supportive care. The patient, a 41-year-old woman, had SDS and developed a type of breast cancer that was hormone receptor-positive and HER2-positive. This means that the cancer was driven by specific hormones and proteins, which made it treatable with targeted therapies. Because of her SDS and underlying bone marrow issues, her doctors had to carefully adjust her treatment plan to avoid making her bone marrow problems worse. She was treated with chemotherapy drugs along with granulocyte colony-stimulating factor (G-CSF) to help her body make more white blood cells and reduce the risk of infections. After nine cycles of treatment, she achieved a complete response, meaning no cancer was detected. Treating solid tumors like breast cancer in patients with SDS can be particularly challenging because of their underlying bone marrow problems and increased sensitivity to chemotherapy. Many SDS patients have low levels of important blood cells (i.e. neutrophils), which makes it difficult to handle standard chemotherapy. Chemotherapy can further lower these blood cell counts, increasing the risk of severe infections and other complications. The use of G-CSF, which helps the bone marrow produce more white blood cells, can be helpful but comes with its own risks. In some cases, G-CSF might increase the chance of developing leukemia in patients with SDS, especially those with certain acquired (or somatic) genetic mutations. This risk in not well established and subject to controversy in the medical community. In any case, careful monitoring is needed to balance the benefits of cancer treatment with the potential risks. In this case, the patient was able to tolerate chemotherapy with the help of G-CSF, and her cancer responded well to treatment. However, she will need to be closely watched for any signs of blood cancers in the future, as the long-term effects of G-CSF use in SDS patients are not fully understood. For patients with SDS who develop solid tumors, it’s important to have a personalized treatment plan that takes into account these unique health challenges. Collaboration with SDS experts ins highly encouraged. Overall, this case highlights the possibility of successfully treating solid tumors in patients with SDS, but it also emphasizes the need for careful management of their underlying blood disorders. While this patient had a positive outcome, ongoing research and close follow-up are essential for understanding the best ways to treat cancer in this rare group of patients. We have reached out to the authors to offer our resources and support to the patient. Morecroft R, Logothetics CN, Tarnawsky SP, Davis AA. Chemotherapy-induced neutropenia management in a patient with metastatic breast cancer and Shwachman-Diamond syndrome (SDS): a case report. Transl Breast Cancer Res. 2024 Jul 22;5:26. PMID: 39184925 . Do you enjoy the SDS & Science Snapshots? You can Sign up by using the button on the top right of this post:

In this issue: Discover how tiny zebrafish are having a large impact on SDS research and treatment development! Welcome to our timely updates on all things SDS, Science, and Advocacy. We bring you a digest of recent scientific publications, conferences, and other newsworthy content - all relevant to SDS - with links to more details and learning opportunities. Are you interested in anything specific? Did we miss something? Let us know. Email genetics@SDSAlliance.org or message us on Facebook! This is all for you! Understanding Shwachman-Diamond Syndrome Through Zebrafish Research Shwachman-Diamond syndrome (SDS) is usually caused by mutations in the SBDS gene, but some patients have mutations in another gene called DNAJC21. Because SDS is so rare, and mutations in DNAJC21 are even more rare, researchers often use animals, known as model organisms, like fish, mice, fruit flies, or other animals to study it. Using model organisms to study SDS and other rare diseases helps scientists better understand the disease and develop potential treatments. This is why SDS Alliance, in collaboration with the Jackson Laboratory, is committed to generating a mouse model  with mutations in the SBDS gene that scientists can use to understand SDS and ask important questions that will advance treatment development for SDS. In the SDS & Science Snapshot this week, we are highlighting a new study published by scientists at the CHEO Research Institute (Ottowa, Canada) and colleagues  which used zebrafish, a different model organism than mice, to investigate the impact of germline mutations in DNAJC21 on the development of SDS-related symptoms and identify potential treatment opportunities. Why Zebrafish Are Important for SDS Research Zebrafish are tiny fish that are often used in research because they share many genetic similarities with humans. Their fast growth and transparent embryos make them ideal for studying how genes work, particularly in conditions which affect the blood and bone marrow (like SDS). The use of zebrafish as a model organism for SDS and SDS-associated conditions is not new – zebrafish have been used as a model organism for SDS in previous research studies as well ( here is a link to one example ). In this study, scientists used zebrafish to model SDS caused by mutations in the DNAJC21 gene. By creating zebrafish with similar mutations, researchers can observe the effects of these mutations in a living organism, which provides valuable insights into how the disease affects humans. For more information about the importance of zebrafish and other model organisms in research, you can watch the video below. Key Findings and Potential New Treatment Opportunities The researchers found that zebrafish with mutations in the dnajc21 gene (the zebrafish equivalent of DNAJC21) showed symptoms similar to those seen in SDS patients. These fish had lower numbers of certain types of blood cells, grew more slowly, and had other health problems. This shows that the dnajc21 gene in zebrafish is important for normal blood cell production and overall growth, just like the DNAJC21 gene in humans. One of the exciting findings from this study is that the researchers identified a new role for the zebrafish dnajc21 gene in controlling the production of nucleotides, which are the building blocks of DNA and RNA. When nucleotide levels were low (as a result of mutations in the dnajc21 zebrafish gene), the zebrafish developed problems with blood cell production. However, when the researchers gave the fish extra nucleotides, their blood cell counts improved. This suggests that treatments aimed at increasing nucleotide levels might help manage SDS symptoms in humans. The Role of p53 and its Impact on SDS The study also explored the role of another gene shared between zebrafish and humans, TP53, which is known to be involved in cancer and cell death. When the researchers introduced a somatic tp53 mutation into the dnajc21-mutant zebrafish, they observed some improvement in blood cell counts. However, this also led to other problems, like the development of myelodysplastic syndrome (MDS), a condition where blood cells don’t mature properly and can lead to leukemia. This finding highlights the complex relationship between different genes in SDS and how they can influence the disease’s progression. For more information, you can review this previous SDS & Science Snapshot  which discusses another study investigating the role of acquired (or somatic) TP53 mutations in individuals with SDS. What This Research Means for SDS Patients and Families Although this research is still in the early stages, it provides a valuable foundation for future research studies and potential new treatments development. Research using zebrafish and other model organisms help scientists understand SDS better and offers hope for new treatments . By uncovering how different genes contribute to SDS and SDS-associated conditions, researchers can develop more targeted therapies. For patients and families living with SDS, these findings are a step forward in finding ways to navigate life with SDS and improve treatments. Ketharnathan S, Pokharel S, Prykhozhij SV, Cordeiro-Santanach A, Ban K, Dogan S, Hoang HD, Liebman MF, Leung E, Alain T, Alecu I, Bennett SAL, Čuperlović-Culf M, Dror Y, Berman JN. Loss of Dnajc21 leads to cytopenia and altered nucleotide metabolism in zebrafish. Leukemia. 2024 Aug 13. Epub ahead of print. PMID: 39138265 . Do you enjoy the SDS & Science Snapshots? 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In this issue: SDS Alliance highlights the patient voice at the international INNOCHRON meeting in Greece! 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: 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, 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, 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. The EuNet-INNOCHRON Action developed into a very successful network and interactive community , thanks to a number of dedicated scientists who looked into detail into current and future aspects of neutropenia, enhancing collaborations. Of equal significance, is the opportunity offered to many young clinicians and researchers across the EU including inclusiveness target countries and near neighbor countries to train in the field of neutropenias, a rare-disease condition which often leads to pre-leukemia. Highlights Prof. Helen Papadaki 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. Thanks to the network’s work, patients have a better chance of receiving proper treatment in their place of residence. Furthermore, we have at our fingertips big data and to harvest information critical to define treatments including molecular structure of the disease, biomarkers and other parameters which aid in the prevention, diagnosis and proper monitoring of the patients’ condition. - Dr. Papadaki concludes 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. Do you enjoy the SDS & Science Snapshots? You can Sign up by using the button on the top right of this post:

In this issue: New research genetic testing opportunity for individuals suspected to have SDS! Welcome to our timely updates on all things SDS, Science, and Advocacy. We bring you a digest of recent scientific publications, conferences, and other newsworthy content - all relevant to SDS - with links to more details and learning opportunities. Are you interested in anything specific? Did we miss something? Let us know. Email genetics@SDSAlliance.org or message us on Facebook! This is all for you! SDS Alliance Announces Collaboration with Rare Genomes Project Timely and accurate diagnosis of Shwachman-Diamond Syndrome (SDS) is critical for patients to access optimal care, education, and community support. We are excited to announce our new collaboration with the Rare Genomes Project (RGP)  at the Broad Institute of MIT and Harvard. The RGP is a free and remote research program using genomic sequencing to look for the genetic cause of rare diseases, such as SDS. Eligible families will be asked to provide a blood sample and medical information. If a result is found, the RGP team will work with your doctor to confirm the result. What is the purpose of this study? The Rare Genomes Project is a research study focused on patients and families with rare and genetically undiagnosed conditions, now including those suspected to have SDS. The RGP uses genomic sequencing to search for the cause of rare disease in these families and hopes to accelerate the rate of rare disease diagnosis in the process.  How is the genetic sequencing done? What is particularly exciting about this project is that it uses Whole Genome Sequencing (WGS), sequencing the entire genome, not "just" the coding sequences called as genes (as in Whole Exome Sequencing (WES)) but also everything in between. Are you curious how WGS is done? Check out this short video overview, below. For more details about the difference between WGS and WES, check out this video . Who is eligible to participate in our new collaboration? Those who have a clinical suspicion for SDS, including a history of two or more of the symptoms listed below . (“A history of'' means that these symptoms may have happened in the past and resolved by the time participation in the RGP is considered.) Exocrine pancreatic insufficiency (EPI): Decreased pancreatic enzymes (serum trypsinogen or pancreatic isoamylase), decreased fecal elastase, malabsorption, or steatorrhea Hematologic abnormalities: Cytopenias including neutropenia, hypocellular bone marrow, bone marrow failure, or MDS/AML Skeletal dysplasia: Rib cage/thoracic abnormality, metaphyseal dysostosis, extremity abnormalities, scoliosis, or abnormal bone density Individuals with a suspected genetic cause that has not been identified due to prior testing being negative or inconclusive OR a lack of access to genetic testing . ( This means that patients who have received genetic testing previously ARE eligible to participate, as long as prior testing has not yielded a diagnosis.) Applicants for the RGP must live in the United States . How do I get involved? Participation is initiated by eligible patients and families by completing an online application which asks questions about personal and family medical history. The RGP research team will review your application to determine eligibility - this application review process may include a request for additional medical records. Eligible families will also be invited to participate in a virtual introductory meeting to meet the RGP team and discuss participation details such as submitting a blood sample. For more information, you can watch the video below or visit this webpage on the RGP website . Will I receive genetic testing results? The goal of the RGP-SDSA collaboration is to find the genetic explanation for SDS in each family who enrolls, but the RGP cannot guarantee that they will have a result for each family. Because this is research-based genetic testing, the process is expected to take longer than routine genetic testing. If the RGP finds a genetic variant(s) that may explain SDS in the family member with the condition, the RGP team will work with affected individuals to clinically confirm and return the results. The RGP does not return results to unaffected family members. How will I receive genetic testing results? If the RGP finds results that they believe explains the underlying cause of SDS present in your family, they will contact you and ask if you would like to have the findings clinically confirmed in a CLIA-certified laboratory. A genetic counselor on the RGP staff will work with a doctor of your choice to order testing through the CLIA-certified lab. The doctor who orders the clinical test will be the one who shares the results with you. If this project sounds like it could benefit you or a loved one, we encourage you to fill out an application on the RGP website . More resources The SDS Alliance team is available for guidance at connect@SDSAlliance.org .   At SDS Alliance, we have assembled resources for possible patients and their healthcare providers to access no-cost testing options, wherever you are. This page is dedicated to the SDSA partnership with the Rare Genomes Project  to provide access to whole-genome sequencing on a research basis to US residents. If this program doesn't work for you, please check out our other resources or email us at connect@SDSAlliance.org .   Download a printable flyer here, available in English and Spanish: Do you enjoy the SDS & Science Snapshots? You can Sign up by using the button on the top right of this post:

In this issue: Dr. Alan Warren's group reviews cutting edge research on clonal hematopoiesis and its impact on personalized medicine opportunities for SDS. Welcome to our timely updates on all things SDS, Science, and Advocacy. We bring you a digest of recent scientific publications, conferences, and other newsworthy content - all relevant to SDS - with links to more details and learning opportunities. Are you interested in anything specific? Did we miss something? Let us know. Email genetics@SDSAlliance.org or message us on Facebook! This is all for you! Understanding the Role of Blood and Bone Marrow Stem Cell Mutations and Their Impact on SDS Progression and Treatment Shwachman-Diamond Syndrome (SDS) is a rare genetic disorder that affects the bone marrow, pancreas, and skeletal system. Recently, researchers have made significant strides in understanding how somatic (or acquired) genetic mutations play a role in the bone marrow failure of patients with SDS. Dr. Alan Warren and his team recently published a review of these advancements in Blood , the official journal of the American Society of Hematology.  One study highlighted in this review  used advanced techniques to map relationships between the blood and bone marrow stem cells in patients with SDS, shedding light on the mutations that may influence the development and progression of MDS and AML. This was done by analyzing individual stem cells from the blood and bone marrow of ten SDS patients aged 4 to 33 years. Researchers discovered that most of these patients had large groups of bone marrow stem cells with a lot of somatic (or acquired) genetic mutations, such as mutations in the TP53 gene, a pattern usually seen in much older individuals. This suggests that blood and bone marrow stem cells in SDS patients are affected early in life, contributing to the development of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) at younger ages.  Another recent finding highlighted by this review, was the role of acquired (somatic) mutations and how the different somatic mutations interact. While acquired (somatic) mutations were common in the blood and bone marrow stem cells of patients with SDS, not all somatic mutations led to severe consequences. Interestingly, some somatic mutations seemed to help cells survive better despite the SDS-related defects. These "rescue" mutations potentially lower the risk of disease progression to MDS or AML. However, when acquired TP53 mutations occur in both copies of the gene, it can lead to severe conditions like MDS or AML. For more information regarding the development of clones and the difference between somatic and germline variants, watch the video below or review these previously published SDS & Science Snapshots ( Somatic and Germline Variants  or The Difference between Germline and Somatic Genetic Testing ). The review published by Dr. Warren and his team shared that multiple recent studies have had similar findings, reporting that up to 72% of SDS patients often develop clonal hematopoiesis (CH). CH happens when some blood and bone marrow stem cells with specific “signatures” of acquired (or somatic) mutations start to dominate, but other features of MDS and AML are not present in the bone marrow. The acquired CH mutations observed in SDS patients were usually different from those seen in older adults without SDS. By tracking these mutations over time, researchers hope to better understand how they affect disease progression from CH to MDS and AML. For more information about clones, how they develop, and how to monitor the development of them, watch the video below. Dr. Warren and his team emphasized the timing of when these somatic mutations occur is also crucial. By building a "family tree" of stem cell mutations, researchers can estimate when specific mutations happened. Some mutations in SDS patients can occur very early, even before birth. Following the “family tree” of somatic mutations and how they relate to early somatic mutations highlights the importance of monitoring SDS patients from a young age. Dr. Warren presented part of this work and background virtually as part of the 2024 Expert Webinar Series, hosted by our Australian partner organization, Maddie Riewoldt's Vision , focused on funding research to discover cures for Bone Marrow Failure Syndromes. For families and patients with SDS, these findings emphasize the importance of regular bone marrow biopsies and somatic genomic testing (also known as NGS)  on these bone marrow biopsy samples and/or on peripheral blood samples. Understanding which somatic mutations are present in the blood and bone marrow of SDS patients can help doctors predict the risk of disease progression and make informed decisions about treatments, including the potential of bone marrow transplant. As research advances, it may also lead to new therapies that target specific somatic mutations or pathways, offering hope for better outcomes in the future. Cull AH, Kent DG, Warren AJ. Emerging genetic technologies informing personalized medicine in SDS and other inherited bone marrow failure disorders. Blood. 2024 Jun 21:blood.2023019986. Epub ahead of print. PMID: 38905596 . Do you enjoy the SDS & Science Snapshots? You can Sign up by using the button on the top right of this post:

In this issue: New research with induced pluripotent stem cells is shedding new light on our understanding of SDS! Welcome to our timely updates on all things SDS, Science, and Advocacy. We bring you a digest of recent scientific publications, conferences, and other newsworthy content - all relevant to SDS - with links to more details and learning opportunities. Are you interested in anything specific? Did we miss something? Let us know. Email genetics@SDSAlliance.org or message us on Facebook! This is all for you! Unlocking the Secrets of Early Development in SDS with Induced Pluripotent Stem Cells Shwachman-Diamond syndrome (SDS) is a rare genetic disorder that affects the bone marrow, leading to a shortage of blood cells. It can also cause other problems in the body and increase the risk of leukemia, a type of cancer. The disorder is mainly caused by mutations in the SBDS gene, which is important for making ribosomes, the cell’s protein factories. Without proper SBDS function, not enough ribosomes can form, leading to many of the issues seen in SDS. In the SDS & Science Snapshot this week, we are highlighting a recent study led and published by Dr. Yigal Dror , a leading physician-researcher on inherited bone marrow failure syndromes from The Hospital for Sick Children (SickKids in Toronto). In this study, Dr. Dror and his research team wanted to find out exactly when the blood cell problems of individuals with SDS begin during development with the hopes of guiding future research in therapy development. To do this, Dr. Dror and his research team created a special type of cell called induced pluripotent stem cells (iPSCs) using cells from bone marrow samples from SDS patients and healthy controls, which can turn into any cell type in the body. This ability to “shape shift” makes iPSCs a powerful tool for studying early embryonic development, as they can be used to observe how diseases or genetic conditions affect the formation of different cell types from the very beginning. Additionally, iPSCs can be used to model diseases in the lab, allowing scientists to explore new treatments and understand the underlying mechanisms of various disorders without the need for embryonic stem cells. For more information about the important use of iPSCs in research, you can watch the video below. Key Findings from this Study: Lower Efficiency in Cell Reprogramming : The researchers found that it was much harder to create iPSCs from SDS patients compared to heathy donors, suggesting that cells from SDS patients are either less fit or have a reduced ability to be reprogrammed into stem cells. Defects in Blood Cell Formation : When the iPSCs from SDS patients were encouraged to become blood cells, they formed far fewer blood cells than the healthy iPSCs. This means that the blood cells in SDS patients have trouble developing properly, which can explain the issues with healthy blood cell development (like neutropenia) seen in SDS patients. Early Developmental Issues : The study also showed that the problems start at a specific stage of blood cell development, known as the early emerging hematopoietic progenitors (EHPs) stage. This is an early step in the process where stem cells start to become specialized blood cells. SDS cells had fewer EHPs, and these cells were less able to grow and multiply. Potential for New Treatments:  One exciting aspect of this study is that the researchers found that adding back the SBDS gene to the SDS iPSCs improved their ability to form blood cells. This suggests that gene therapy, which aims to correct the defective gene, might be a promising treatment for SDS. Additionally, understanding the specific stages and processes affected by SDS helps in designing drugs that can target these problems more precisely, and provides a rationale to apply treatments as early in life as possible. Mapping Gene Pathways in SDS: Lastly, the researchers in this study investigated the gene expression during early development of these iPSCs from SDS patients. By analyzing these iPSCs, they identified important genes and cellular pathways that are activated or repressed at various stages of cell development. This detailed mapping of gene activity may help in understanding the differences between healthy and SDS iPSCs, providing valuable information for developing targeted therapies for SDS. Understanding exactly when and how blood cell problems start in those with SDS can help scientists develop better, more effective treatments. By knowing that the defect begins at the EHP stage, researchers can target this stage to find ways to prevent or correct these defects. These findings could help lay the groundwork for new therapies that can improve blood cell production in SDS patients, reducing the need for frequent treatments and improving quality of life. This also underscores the critical importance of early and accurate diagnosis of SDS, so that any treatment can be started as early in life as possible, when the benefits may be the biggest. With continued research, there is potential for significant improvements in managing and treating SDS! Lagos-Monzon A, Ng S, Luca AM, Li H, Sabanayagam M, Benicio M, Moshiri H, Armstrong R, Tailor C, Kennedy M, Grunebaum E, Keller G, Dror Y. Aberrant early hematopoietic progenitor formation marks the onset of hematopoietic defects in Shwachman-Diamond syndrome. Eur J Haematol. 2024 Jul 5. PMID: 38967591 . Do you enjoy the SDS & Science Snapshots? 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