In this issue: Ribosomes in Mitochondria. Therapies and Cures start with an Accurate Diagnosis - what are we doing about increasing the speed and access. Welcome to our weekly updates on all things SDS and Science. 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 connect@SDSAlliance.org or message us on Facebook! This is all for you! New publication on Ribosomes in Mitochondria in Nature Communications, a collaborative project by Drs. Alan Warren and Michal Minczuk's teams. Our cells contain many different organelles necessary for cell function and therefore, life. We in the SDS community are mostly focused on ribosomes, the organelles in the cells that are responsible for translating the genetic information on the mRNA into proteins. In SDS, there is a problem with building these ribosomes, because there is not enough of an essential component (the SBDS protein) that is involved in the complicated ribosome-assembly process. Typically, when we talk about ribosomes, we mean the ribosomes that are in the cytoplasm or on the endoplasmic reticulum, i.e. the ribosomes that are translating nuclear genomic information into most of the proteins present in our cells. But, our cells have in fact another set of ribosomes: ribosomes within another set organelles called mitochondria. 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. See the two videos below to learn more about mitochondria and their role in energy metabolism. This current publication talks about very detailed work on how components of the mitochondrial ribosomes are modified and regulated. The article titled "A late-stage assembly checkpoint of the human mitochondrial ribosome large subunit" can be downloaded, here: Nature Communications volume 13, Article number: 929 (2022). Tomorrow is Rare Disease Day 2022! Watch out for our special edition newsletter (coming soon) with Rare Disease Day (and month) highlights! Therapies and Cures start with an Accurate Diagnosis - what are we doing about increasing the speed and access. Most of us in the rare disease community are painfully aware how difficult and long the process of getting a correct and accurate diagnosis can be. Hence the term "Diagnostic Odyssey". Source: https://www.raconteur.net/infographics/the-diagnostic-odyssey/ The average time to a correct and accurate diagnosis is about 5 years, and requires visiting multiple specialist. Source: https://rarediseases.org/new-patient-journey-infographic-gives-a-glimpse-into-the-diagnostic-odyssey/ For us at the SDS Alliance, increasing the efficiency of SDS and rare disease diagnosis is a top priority, because it will reduce the suffering of individuals and their families, enabling access to best treatments and support provide patients the opportunity to participate in natural history studies and voice their needs and priorities provide the opportunity to help in the therapy development process by participating in research and providing data and samples And how are we approaching this? Because SDS is very rare, our strategy is to "ENABLE ACCIDENTAL DIAGNOSES". That is, instead of trying to educate a handful of specialists about SDS only, we are investing into making sure SDS genes (in particular SBDS) is covered on as many diagnostic panels as possible, so that doctors can stumble upon SDS even if they don't think of specifically testing for it educate current hematology, immunology, and GI specialist about rare disease in general, including SDS changing how the next generation of doctors think about rare disease. You may have heard the saying: when you hear hoofbeats, think horses, not zebras. We need the medical community to be aware and consider zebras sooner and more widely, once they rule out horses. This will be a win-win for everyone involved. More information on all our initiatives coming soon. If you or your loved one already suspect SDS and needs help accessing diagnostic tools and provides, please reach out to us. We have identified resources anywhere in the world to help you with specialists and financial support, if needed. Email us at connect@SDSAlliance.org Repeat: PubMed overview What is PubMed.gov, you may ask? Check out this nice summary from McGill University. The SDS research community is small, so we don't expect SDS specific scientific publications every week, and not every new publication is relevant. But if there are any good ones, we will cover them in this section of snapshot posts. If you need access to a full text article, and its not available through the PubMed link, we may be able to help you. Email us at library@SDSAlliance.org. Here is a quick over view of what PubMed is and how it works. Did you enjoy this first edition of the SDS & Science Snapshots? You can Sign up by using the button on top:

In this issue: What are biomarkers and why are they important? Rare Diseases: Maintaining Momentum (From The Lancet). Introduction of PubMed. Welcome to the first edition of our weekly updates on all things SDS and Science. 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? Please let us know! This is all for you! What are biomarkers and why are they important? As we continue to expand the toolbox by investing into critical tools and infrastructure for SDS research, let's take a look what biomarkers are and why they are so important. In the video below, Dr. Janet Woodcock of the U.S. FDA states simply: “biomarkers are characteristics of the body that you can measure.” Discovering new biomarkers is a crucial step in both diagnosing disorders as well as evaluating potential treatments. Biomarkers are used in clinical trials to measure how well the body responds to the potential treatment. Without it, we won't be able to tell if a treatment has any benefit at all. Examples of biomarkers include your basic blood pressure, heart rate, and blood counts such as ANC (neutrophil count), but also more complex markers within our bodies that may be especially relevant for SDS. Dr. Woodcock stresses how crucial it is to improve the clinical trial process and success rate by identifying novel biomarkers so scientists can tell earlier on whether an investigational drug is safe and effective. Another important consideration is how the biomarkers we measure translate to actual improvement to the quality of life of patients. Rare Diseases: Maintaining Momentum (From The Lancet) Affecting over 300 million people worldwide, rare diseases are hardly rare. Many are difficult to diagnose, and SDS is no exception. These challenges have been compounded during the COVID-19 pandemic, which, in Europe, resulted in more than 80% of patients having essential consultations cancelled... and the situation in North America is similar. Nevertheless, there is cause for hope. According to a new report from Global Genes, a leading rare disease advocacy organization - yes, the SDS Alliance is a member - , investment in rare diseases has increased sharply. In 2021, drug developers invested a total of US$22·9 billion for research on rare disorders, an increase of 28% compared with 2020. "The International Rare Diseases Research Consortium (IRDiRC), a public–private partnership, aimed to achieve two main objectives by 2020: to diagnose most rare diseases and to deliver 200 new therapies. The latter goal was achieved in 2017, 3 years ahead of schedule, and the goal for diagnostics is within reach. Looking to the future, IRDiRC have set three new ambitious targets for the next decade: for all patients coming to medical attention with a suspected rare disease to be diagnosed within 1 year and all currently undiagnosable individuals to be able to enter a research study; for 1000 new therapies for rare diseases to be approved; and for methodologies to assess the impact of diagnoses and therapies on patients. Through the work of ongoing and new multi-stakeholder initiatives, these targets are within reach." We are working hard to make sure SDS is part of this revolution. One such initiative is the Patient Identification and Engagement for RARE CNS Disorders (PIE4CNS) multi-stakeholder initiative, which aims to address barriers to timely diagnosis and to engagement of patients with clinical research in gene therapy and other promising novel technologies. We are grateful to have had the opportunity last year to participate in this effort, and look forward to help with the next stage as well. Collaboration is essential to avoid geographic or disease-based silos. In this respect, the European Reference Networks have been instrumental in facilitating the exchange of knowledge between health-care professionals across borders, ameliorating diagnosis and care, and will also be helpful to facilitate recruitment of patients across countries for future trials. Over the past several months, we have expanded our collaboration with the European SDS and neutropenia research community. We will share more, soon. New on PubMed What is PubMed.gov, you may ask? Check out this nice summary from McGill University. The SDS research community is small, so we don't expect SDS specific scientific publications every week, and not every new publication is relevant. But if there are any good ones, we will cover them in this section of snapshot posts. If you need access to a full text article, and its not available through the PubMed link, we may be able to help you. Email us at library@SDSAlliance.org. Here is a quick over view of what PubMed is and how it works. Did you enjoy this first edition of the SDS & Science Snapshots? You can Sign up by using the button on top:

Lisa lives on Long Island, New York, with her husband and four daughters. Her two youngest daughters, Nora and Kayla, were genetically diagnosed with SDS after an extensive diagnosis journey - read their story, here. Lisa is a Special Education Teacher at Half Hollow Hills High School West in Dix Hills, New York. She has certifications from Birth-12th grade in Special Education, General Education, and English Language Arts and has a masters in Literacy. Lisa is passionate about helping the SDS community by supporting research and helping families advocate for their children. She jumped into action on the very same day her first child was diagnosed, raising funding, researching resources, and connecting with SDS families everywhere, and has not stopped ever since. Her drive and creativity have inspired countless other families to engage and she is an unstoppable positive driving force toward therapies and cures for people with SDS everywhere. ​ In her role as the new Family and Community Engagement Ambassador on the SDS Alliance Team, Lisa helps find and support new SDS families, identify and offer new resources for families, and develop family educational materials and events.

Woburn, MA (November 3rd, 2021) — The SDS Alliance is delighted to announce that the organization has been awarded a prestigious grant from the Chan Zuckerberg Initiative (CZI). The SDS Alliance is chosen as one of the 20 selected organizations from more than 200 applicants to be awarded the CZI “Rare As One” grant for organizational capacity building. Each grantee will be awarded $600,000 total over the next three years. “For biomedical research in rare diseases to advance quickly and effectively, patients must be full partners with scientists and clinicians in research,” said CZI Head of Science Cori Bargmann. “We’re proud to expand our cohort of Rare As One grantees and further support the rare disease ecosystem as we work towards diagnosis, treatments, and cures together.” “Patients are experts in their own diseases, and their knowledge and commitment to advancing progress in their disease areas has the power to center patient priorities and dramatically accelerate the pace of research,” said Heidi Bjornson-Pennell, CZI Rare As One Program Manager. “The RAO Network is proud to lift up these efforts by offering new tools, funding, and capacity-building support and training to help these organizations grow and scale.” “We are incredibly humbled and grateful to be given this opportunity to advance the development of international collaborative research infrastructure, strengthen our organizational capacity, implement our patients’ priorities, and work synergistically with our research community — specifically for the benefit of our patient community,” said Dr. Eszter Hars, President and CEO of the SDS Alliance. “We wouldn’t have won this prestigious grant award without our community’s support for our research initiatives, the mouse model project being a prime example. This grant has demonstrated that with proper management and expertise, our community’s donation can be leveraged to create significantly more impact than the face value of the donation would allow. This grant award is also a substantial endorsement of our strategy to drive SDS research. Research and therapy development is a very expensive endeavor, and we absolutely need to use any donation we receive wisely and leverage the funding we have whenever possible,” said Dr. Hars. “Although this award is an important acknowledgement of our efforts, there is so much work to be done. The SDS Alliance will continue to execute our strategy to drive research toward a cure.” This grant will allow the SDS Alliance to roll out new patient-led projects as soon as early 2022. About the Shwachman-Diamond Syndrome Alliance (SDS Alliance) The SDS Alliance is a 501(3)c nonprofit serving the global SDS community, driving research to cure SDS by taking concrete steps to deliver new therapies that prevent bone marrow failure, leukemia, and other problems of SDS — turning HOPE into ACTION, and action into RESULTS. For more information, please visit www.SDSAlliance.org. About the Chan Zuckerberg Initiative The Chan Zuckerberg Initiative was founded in 2015 to help solve some of society’s toughest challenges — from eradicating disease and improving education, to addressing the needs of our local communities. Our mission is to build a more inclusive, just, and healthy future for everyone. For more information, please visit www.chanzuckerberg.com.

At the end of September, we conducted the second annual global virtual fundraiser to support SDS research. The theme this year was TWO MILLION STEPS CLOSER TO #CURESDS. When? September 20st-26th, 2021 Where? Virtual! Run/Walk/Roll wherever you like! What? Fun!!! Fundraise and Run/Walk/Roll in your community! Why? To build community and raise funds for SDS research! How? (Registration is now closed). Since you are here, you are likely already registered. Now just get hooked up to the leaderboard! The vibrant blue T-shirts were hugely popular and were included for participants who registered by the cutoff date is August 29th, 2021. Will they become a collectible?!? Results: And just like that, it's a wrap. The conclusion of the 7-day long challenge: TWO MILLION STEPS CLOSER TO #CURESDS is worth celebrating. You stepped up big time and logged - drumroll please! - 3.6 MILLION STEPS! With your support, we have also exceeded the fundraising goal of $10,000 for this fundraiser. This fundraiser pushed us over the milestone of reaching 70% of our funding goal for the Mouse Model Project. Since then, we reached 85%. Will you help us get to a 100%? Less than $25K to go. Together, we can get there. Let's turn hope into action, now. Learn more here. Winner of the team challenge: Winner of the individual challenge: Here is what she shared with us: "It was a pleasure to participate in the Two Million Step challenge with our Team at Frost Brown Todd and Al’s Pals. My husband and I were on a family vacation with my 2 sons, their wives, and our 8 grandchildren so putting in steps was not a challenge at all, it was a gift. Every step taken was a step of hope. Looking forward to participating for many years to come. All the best -- Cindy" Making Memories A personal diary by the founders Day 1. Evening stroll to break in our brand new #CureSDS shirts and launch into the TWO MILLION STEPS challenge! It's not too late to join! Register here to support SDS research. #StepsToCureSDS Day 2. Ripple effect. We are turning HOPE into ACTION. Several SDS families have already joined us, from around the world. (You know who you are ). How many more families and organizations will step up to the plate? Together, we can make huge strides toward therapies and cures for Shwachman-Diamond Syndrome. Will you join us? Day 3. It's a balancing act. I mean life...as a rare disease parent. There is work, there is raising kids and making sure they get the best care possible, and then there is driving research to #CureSDS. Rare disease research faces specific challenges, most notably funding. In the current paradigm, we - the rare disease families - have to be the agents of change. Is it hard? Yes. Are we doing it anyway? Absolutely. We need to be proactive, fundraise, and be active participants in research. We have got what it takes: the right expertise, experience, vision, plan, and drive. Join us! Register or donate here. Team: https://www.sdsalliance.org/meet-the-team Vision: https://youtu.be/NAgCRImReXk Plan (Strategy & Roadmap): https://www.sdsalliance.org/strategy-roadmap Day 4. Together we can. None of us could log TWO MILLION STEPS single-handedly, but together we will. There is still time to join, see below. We created the SDS Alliance to bring the whole global SDS community together to work towards our common goal of a brighter future for all SDS patients. We do this by driving research to #CureSDS, and invite all families, organizations, academics, and industry who want to help to join us. Register or donate here. Team: https://www.sdsalliance.org/meet-the-team Vision: https://youtu.be/NAgCRImReXk Plan (Strategy & Roadmap): https://www.sdsalliance.org/strategy-roadmap Day 5. There is a path to #CureSDS. It may not be easy or straightforward, but with focus, determination, and purpose, we can get there. We are already TWO MILLION STEPS closer, thanks to all of you, turning HOPE into ACTION. There is still time to join. Register or donate here. Team: https://www.sdsalliance.org/meet-the-team Vision: https://youtu.be/NAgCRImReXk Plan (Strategy & Roadmap): https://www.sdsalliance.org/strategy-roadmap Day 6. It is all about the SDS patients: young, old, and everyone in between. What do we need to set in motion TODAY to create a brighter FUTURE for all SDS patients? That's what the SDS Alliance is focused on. See our roadmap below. With your contribution to the TWO MILLION STEPS CLOSER TO #CURESDS challenge, you are part of the solution. Thank you! This challenge ends tomorrow night, but there is still time to join. Register or donate here. Strategy and Roadmap to Therapies and Cures for SDS: https://www.sdsalliance.org/strategy-roadmap Vision: https://youtu.be/NAgCRImReXk Team: https://www.sdsalliance.org/meet-the-team Day 7. And just like that, we arrived at the summit. The conclusion of the 7-day long challenge: TWO MILLION STEPS CLOSER TO #CURESDS is worth celebrating. You stepped up big time and logged - drumroll please! - 3.6 MILLION STEPS! With your support, we have also exceeded the fundraising goal of $10,000 for this fundraiser. We will announce the winners of the challenge categories, shortly. Thank you, everybody. See you again at next year's event! #StepsToCureSDS

From the Founder, Dr. Eszter Hars, Ph.D. This week, I had the incredible honor to be invited to speak at the 2021 Global Genes RARE Patient Advocacy Summit, one of the world’s largest gatherings of rare disease patients, healthcare professionals, researchers, advocates and allies, which took place virtually September 27-29, 2021. Presenting on the panel session focused on "Developing Impactful and Relevant Communication and Education Tools for Your Community" allowed me both to raise awareness about Shwachman-Diamond Syndrome and our amazing community, and share my passion for translating and communicating science to empower patients to advocate for themselves and for therapy development. For rare disease communities, patient, caregiver, and physicians, education is often one of the core elements of advocacy work. This session offered tactical insights on developing impactful educational materials, programs, and tools around relevant topics for patient communities. Demystifying emerging science and complexities of healthcare with accessible content Empowering patients, families, and caregivers to advocate for themselves in care and research Thinking outside the box – understanding how to build the right tools to fit your community The RARE Patient Advocacy Summit provides participants with the opportunity to gain insight into the latest rare disease innovations, what’s on the horizon, and what individuals, advocacy leaders and communities can do to accelerate progress. It creates opportunities for stakeholders in rare diseases to connect, work together, share information, knowledge and resources, and build relationships to support and sustain collaboration beyond the Summit. Indeed, I feel so lucky to have been able to catch up with so many inspiring leaders and connect with so many new opportunities. “This is a pivotal moment for progress in rare disease,” said Craig Martin, CEO of Global Genes. “We are excited to see numerous promising advancements in science and technology, which are leading us toward better understanding, diagnosis and treatment of rare diseases. Yet we also need to work together now to ensure that these innovations can inclusively and equitably benefit patients around the world as they become available. The RARE Patient Advocacy Summit provides an opportunity for the community to learn, connect and engage around topics and initiatives of importance.” For more information and to register (to access the recordings), please visit: https://globalgenes.org/event/patient-summit/ About Global Genes® Global Genes is a 501(c)(3) non-profit organization dedicated to eliminating the burdens and challenges of rare diseases for patients and families globally. In pursuit of our mission, we connect, empower, and inspire the rare disease community to stand up, stand out, and become more effective on their own behalf ⁠— helping to spur innovation, meet essential needs, build capacity and knowledge, and drive progress within and across rare diseases. We serve the more than 400 million people around the globe and nearly one in 10 Americans affected by rare diseases. If you or someone you love has a rare disease or are searching for a diagnosis, contact Global Genes at 949-248-RARE or visit our Resource Hub.

From the Founder, Dr. Eszter Hars, Ph.D. This week, I had the great honor to be invited to speak on a patient-centered panel at the NICER Symposium, alongside other accomplished patient advocates. I shared my family's experience with pursuing my daughter's diagnosis to highlight opportunities to shorten the diagnostic odyssey and call for the medical community to consider genetic causes of hematological and immunological (and gastroenterological) presentations much earlier in the patient journey. The SDS Alliance is working with the NICER consortium on several projects, including providing high impact educational opportunities regarding Shwachman-Diamond Syndrome (SDS) to the medical community and access to diagnostic tool for SDS to providers and patients everywhere. About NICER: North American Immuno-Hematology Clinical Education & Research The mission of the NICER consortium is to provide a collaborative multidisciplinary environment to advance the education, clinical care, and research involving pediatric and adult patients with immuno-hematologic disorders. NICER is committed to being purposefully inclusive of pediatric and adult providers from multiple disciplines including, allergy/immunology, genetics, hematology/oncology, hematopoietic stem cell transplant, rheumatology, infectious disease, gastroenterology, endocrinology, etc. to enrich the educational environment and research goals of the consortium. Their goals include: Establishing a network of clinicians and researchers with interest and expertise, to share ideas, provide care and study patients with immuno-hematologic disorders. Utilizing the collective experiences and the multi-disciplinary expertise within the consortium to provide a unique learning and mentoring environment open to both members and non-members. Leveraging the pooled, diverse resources of the members to create a platform for clinical trials, basic science, and translational research with the development of a clinically annotated database, biorepository and network of member centers unified via a central IRB. Partnering with academic societies, institutes and foundations with mutual objectives, to empower the educational initiatives and accelerate research discoveries in areas related to immuno-hematology.

In 2018, a wonderful friendship unfolded as a result of a mishap. Now the SDS family got an extra super advocate as a result. Read the news articles and watch the newscast from various outlets, using the links below. https://www.fox26houston.com/news/amazon-workers-misplaced-keys-helps-raise-awareness-for-boys-rare-disease https://www.khou.com/mobile/article/news/after-amazon-mix-up-man-becomes-advocate-for-little-boy-with-rare-disease/285-511342480

Gracie - a young adult SDS patient in the US, shares her story on how she found her voice though a beautiful article and her transplant journey through a lively vlog. Thank you, Gracie! Gracie on her "re-birthday" in 2019, when she received her bone marrow transplant. How I Found my Voice though Rare Disease Please read the article I wrote for PatientWorthy.com, here: https://patientworthy.com/2020/02/25/how-my-rare-disease-helped-me-find-my-voice. My advice for new families would be (from the perspective of the patient) to let their child lead as normal of a life as they can. Show them that this disease does not define them and that they can do anything they set their minds to. Instead of keeping their child in the dark and trying to control every decision and every doctor's appointment, educate them on what is going on and how they can care for themselves. Let them make some of the decisions (even if it's just a small one) and let them know that they are and will be entirely capable of caring for themselves. For a sibling dealing with their brother or sister having this SDS, make them aware of the bigger picture. Educate them too on what is going on and why their sibling cannot do certain things. And for parents, make sure the siblings get some attention and love too so they don't resent their sibling with SDS. -- Gracie My Bone Marrow Transplant I created a detailed vlog post about why and how I went though a bone marrow transplnat in 2019. Watch it here: https://youtu.be/DM0GmipSKP8

By Emily Williams / Boston Children's Hospital In this post, you can learn about the passion and efforts of a mother to a young daughter with Shwachman-Diamond Syndrome from the UK. Read the full article here: https://discoveries.childrenshospital.org/cure-shwachman-diamond-syndrome Don't miss the video in the article (linked above), highlighting the research program for Shwachman-Diamond Syndrome and bone marrow failure at Boston Children's Hospital! “I want to be making a difference. I don’t want to be in a position when Poppy is 20 — or at any point — to be told she is developing leukemia and not to have done everything I could. So, I’m doing everything I can now.” says Julia.

By Emily Williams / Boston Children's Hospital In this post, you can learn about the experiences of two families affected by Shwachman-Diamond Syndrome, and about their transplant journeys. Read the full article here: http://discoveries.childrenshospital.org/shwachman-diamond-syndrome-research/ Don't miss the video in the article (linked above), highlighting the North American Shwachman-Diamond Syndrome Registry (SDSR)! “People with SDS have an increased sensitivity toward the chemotherapy used during the bone marrow transplant conditioning process,” says Dr. Shimamura.

Max and his family are raising awareness for Shwachman-Diamond Syndrome and rare disease by participating again in the 2020 Jeans for Genes campaign, in Australia. Thank you!!! Max with his family Video: https://youtu.be/6eUsaZ6X_aw Read Max's story, here: https://www.jeansforgenes.org.au/max-2 And here: https://www.moreechampion.com.au/story/6842741/meet-max-one-of-the-smiling-faces-of-the-2020-jeans-for-genes-campaign/ Finding out that your child has a rare genetic condition [Shwachman-Diamond Syndrome] is hard enough. Discovering that it can progress into even more frightening conditions such as leukaemia and other life-threatening bone marrow disorders was truly terrifying for the family of three-year-old Max.