Search our Site. Find Results Fast.

In this issue: Report of a new variant in DNAJC21 associated with SDS like symptoms; Plus, new FDA Guidance on Patient-Focused Drug Development 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! Report of a new variant in DNAJC21 associated with SDS like symptoms As most of you are aware, over 90% of SDS is caused by bi-allelic mutations in the SBDS gene. We covered that it a recent Snapshots issue. However, there are a few other genes that are implicated in SDS. Except for EFL1, there is no consensus among the science and medical experts whether the syndromes caused by the other genes should be called classic SDS, or rather SDS-like syndromes. DNJC21 is one such gene. It is involved in the pathway of ribosome biogenesis, i.e. the making of active ribosomes. More specifically, it seems to play an important role in building the larger (60S) subunit of the ribosome, ensuring that the "exit tunnel", which is a specific part of it, is properly formed. Just to give you a rough idea about the complexities involved in ribosome biogenesis - with a large set of proteins working together to make it happen - see this figure from Dr. Warren's article from 2018. No, don't memorize it! Just notice all the different proteins and steps involved in building the 60S large subunit alone. Back to this week's publication news. Last week, a collaboration between researchers from Turkey, the US, and the UK identified a new mutation in DNAJC21 that seems to lead to an SDS-like syndrome. DNAJC21 has been implicated in SDS before. What is new here is that the new mutation is in a region of the protein that has previous not been known to be important in this pathway / ribosome biogenesis. You can find the full article, below. A novel missense mutation outside the DNAJ domain of DNAJC21 is associated with Shwachman-Diamond syndrome. Alsavaf MB, Verboon JM, Dogan ME, Azizoglu ZB, Okus FZ, Ozcan A, Dundar M, Eken A, Donmez-Altuntas H, Sankaran VG, Unal E. Br J Haematol. 2022 Mar 17. doi: 10.1111/bjh.18112. Online ahead of print. PMID: 35298850 https://onlinelibrary.wiley.com/doi/epdf/10.1111/bjh.18112 New FDA Guidance on Patient-Focused Drug Development The U.S. Food and Drug Administration recently released guidance for industry and other stakeholders - Patient-Focused Drug Development: Methods to Identify What Is Important to Patients. What is a Guidance? "FDA guidances are documents that explain the agency’s interpretation of, or policy on, a regulatory issue. The FDA prepares guidances primarily for industry, but also for other stakeholders and its own staff, and uses them to address such matters as the design, manufacturing, and testing of regulated products; scientific issues; content and evaluation of applications for product approvals; and inspection and enforcement policies. Although guidances are not legally binding, they show stakeholders one way to reach their regulatory goal. However, stakeholders are free to use other approaches that satisfy the relevant law and regulations. Recently, FDA published a report on how to improve the processes that make these important documents available." ~ says the FDA. New Guidance: Patient-Focused Drug Development: Methods to Identify What Is Important to Patients Guidance for Industry, Food and Drug Administration Staff, and Other Stakeholders This is a must-read for all stakeholders - including us - involved in the drug development process. You can download the entire document, here. Thank you to the FDA and all the stakeholders involved in developing this guidance to improve the process and outcomes for patients in need of treatments. Beyond just reading it, we are proud to share that we have co-signed a letter containing specific suggestions to improve the guidance -- to be more helpful for the patient advocacy community. And to make this rather long document more palatable for all of you, several of our friends in the rare disease community came together to read it out loud for you all. Thank you Kif1A.org for putting it all together! https://youtu.be/oCIY4v78-1c Do you enjoy the SDS & Science Snapshots? You can Sign up by using the button on top right of this post:

In this issue: New report this week about COVID and COVID-vaccine tolerance in SDS patients; Plus, what is HLA and a Haplo-transplant, inspired by a case report of a Haplo-transplant in Japan 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 report published last week about COVID and COVID-vaccine tolerance in SDS patients The COVID-19 poses a significant risk to patients with various chronic medical conditions. It has been a big question since the beginning of the pandemic to what extent SDS patients are at risk, in particular as SDS can cause patients to be immunocompromised due to malignancy or bone marrow failure (BMF). Because patients with SDS can experience neutropenia due to BMF, they carry a higher risk for serious infections - at least bacterial origin - compared with the general population. In this new report, the authors investigate the incidence and severity of COVID-19 in the population of patients with SDS. Participants in the North American SDS Registry received a survey in the summer of 2021. 73 participants responded. Answers were anonymous. 10 participants experienced COVID-19 All participants who developed COVID-19 were symptomatic of infection, with the most common symptoms being respiratory, such as congestion or cough (70%), and fever (60%). The median duration of symptoms was 4.5 days. One of 10 patients required hospitalization, but did not require supplemental oxygen. Most reported having a short duration of symptoms that did not require hospitalization or result in serious virus-related complications. 18 participants received a COVID-19 vaccine, and actually all of them received two mRNA vaccine doses. Arm pain was the most common side effect (66.7%), followed by fatigue (50%), fever and/or chills (38.9%), and muscle aches (33.3%). Five of the 18 recipients (27.8%) reported experiencing no side effects. The authors conclude: "Most patients reported a short clinical course with few requiring COVID-19–directed therapy, and only one requiring hospitalization; none experienced significant complications or severe cytopenias. However, these results cannot be generalized to patients with more severe comorbidities, and the relatively small number of patients described limits our ability to comment on risk of developing serious COVID-19 compared with the general population" Coronavirus disease 2019 and vaccination in patients with Shwachman-Diamond syndrome. Galletta TJ, Loveless SK, Malsch MM, Shimamura A, Myers KC. Pediatr Blood Cancer. 2022 Mar 6:e29647. doi: 10.1002/pbc.29647. Online ahead of print. PMID: 35253346 https://onlinelibrary.wiley.com/doi/10.1002/pbc.29647 What is HLA? What is a Haplo-transplant? Bone marrow or stem cell transplants are always on the mind of the SDS community, as SDS can make it necessary either due to causing bone marrow failure or MDS/leukemia. If it comes to that, many patients rely on the generosity of stem cell donors who sign up with special registries and volunteer to donate stem cells if a patient in need matches with their HLA type. However, many patients can't find a match. More information about the need and donation process is available on our website, here. HLA stands for human leukocyte antigens. HLA are proteins—or markers—on most cells in the body. Our immune system uses HLA to see which cells belong in our body and which do not. These markers are critical for stem cell transplants. The closer the donor's and recipient's HLA type match (are the same), the more likely it is for the recipient to accept the new cells and the new cells not to cause complications (such as Graft versus Host Disease (GvHD)) in the recipient's body. That's why in preparation for a bone marrow transplant, the medical team performs a very thorough search and analysis of potential donors. Unfortunately, many patients in need of a stem cell transplant don't have a suitable donor - a donor who's HLA type matches with theirs nearly identically - in their family or in the general population/ stem cell registries. The chances of this happening are particularly high in populations of ethnic minorities and mixed race patients. This is where haploidentical matches/transplants are coming in. A haploidentical transplant is a type of allogeneic transplant. It uses healthy, blood-forming cells from a half- matched donor to replace the unhealthy ones. This is a type of allogeneic transplant where the donor matches exactly half of your HLA. A haploidentical, or half-matched, donor is usually the recipient's mom, dad, or child. Parents are always a half-match for their children. Siblings (brothers or sisters) have a 50% (1 out of 2) chance of being a half-match for each other. It’s very unlikely that other family members (like cousins, aunts or uncles) would be a half-match. While haploidentical transplant is a newer type of transplant and carries a higher risk of complications such as GvHD or graft failure, it also has some advantages. In particular, because donors are usually a close family members, they are usually very willing to donate and can travel to the medical center where the recipient is, ensuring very fresh stem cells and reducing the chance of delays during transport. They can also be available to donated additional stem cells during recovery, if needed. In many countries, haplo-transplants are preferred due to much higher costs associated with unrelated donors. There are medical centers that specialize in haplo-transplants, and there are many active clinical trials ongoing to improve outcomes. Another alternative are cord blood stem cells. We will cover that in another post. This video covers both options in great detail. New case report of a haplo-transplant in an adult SDS patient In the SDS community, we have only been aware of one successful haplo-transplant. But last week, a new case report from Japan has been published. The authors describe their experience treating a 21-year-old male patient with SDS, diagnosed with SDS genetically, as an adult. He developed acute myeloid leukemia (AML) and received a hematopoietic stem cell transplantation from his father, who is human-leukocytic-antigen-haploidentical. The patient received standard conditioning chemotherapy, total body irradiation, and Graft-versus-host disease prophylaxis. Unfortunately, although the patient achieved a complete remission initially, AML relapsed a year later. He passed away of sepsis. [Haploidentical stem cell transplantation for acute myeloid leukemia associated with adult-onset Shwachman-Diamond syndrome].Uemura Y, Hirakawa T, Matsunawa M, Kozuki K, Saiki Y, Takimoto M, Sano F, Watanabe K, Inoue Y, Arai A. Rinsho Ketsueki. 2022;63(2):94-98. doi: 10.11406/rinketsu.63.94. PMID: 35264508 Japanese. This report highlights the importance of focusing our research on the prevention of AML and our advocacy efforts on early and wide reaching SDS diagnosis of patients. Do you enjoy the SDS & Science Snapshots? You can Sign up by using the button on top right of this post:

In this issue: Genes involved in SDS, autosomal recessive inheritance, and what is a mutation vs. a VUS? 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! What genes are responsible for SDS? Our genomes are organized into 23 pairs of chromosomes, made up of very long stretches of DNA. Genes are shorter sequences on the DNA, and each gene encodes one specific protein. Usually, the name of the gene corresponds to the name of the protein. The gene responsible for over 90% of SDS cases is called SBDS (for Shwachman-Bodian-Diamond-Syndrome), and the protein it encodes is called the SBDS protein. It was discovered by Dr. Johanna Rommens and her team, and published in 2003. Since then, several additional genes have been implicated in SDS, namely DNAJC21, EFL1, and SRP54. This GeneReviews article provides a comprehensive overview. Each of these newer genes account for less than 1% of SDS patients. For about 10% of patients who meet the clinical definition of SDS, no genetic cause has been found thus far. This means that they don't have mutations in any of the genes mentioned above, or have only one mutation (which would only make them carriers). Research is ongoing in several labs around the world to look for additional genes that could be responsible for SDS; and to find additional hard-to-find mutations in the known genes. For example, traditional sequencing techniques are not able to identify large deletions that could have removed parts of the chromosome that contain the SBDS gene, and the patient could appear to have only one mutation. To find such large deletions, specialized testing is needed. Also note, that Analysis of SBDS is complicated by the presence of a highly homologous pseudogene, SBDSP. Please reach out to an experienced SDS specialist or geneticist if these challenges could be relevant to you. We can help you connect with one (email us at connect@SDSAlliance.org). What does it mean to be a carrier, not a patient? SDS is inherited in an autosomal recessive pattern. This means that in order for SDS to happen, both copies of the gene have to lose (or significantly reduce) their function through mutations or deletions. Note: This is actually quite a unique situation is SDS: complete loss of SBDS is not compatible with life. Therefore, all "SBDS" SDS patients have a mutation that greatly reduces the amount of functional SBDS protein, but doesn't completely eliminate it. The splice site mutation c.258+2T>C you may have heard about, or seen in your own genetic reports, is the most common SBDS mutation and can still produce a very small amount of functional SBDS protein. If one copy of the gene is normal (functional), than the cell can make enough protein to make up for the mutated copy of the gene, and the cellular function can be maintained without issues. That is why carriers typically don't show any SDS symptoms. What is a mutation vs. a VUS? Both terms refer to a change in a gene, i.e. a change in the sequence of the 4 bases (A, C, T, G) that make up the genetic code. Our genomes are made up of billions and billions of base pairs of DNA. The majority of the sequence is the same across all humans, but a tiny amount differ (0.01%). That means, such a difference occurs once in every thousand letters of the genome on average. However, due to the negative connotation of the word “mutation,” the human genetics community has started to use a new term: “variant.” The term variant underlines the fact that not all variants are harmful. Sometimes it can be difficult to tell whether a variant is harmful or harmless. The mass screening of genes is called Next Generation Sequencing (NGS). NGS genetic testing involves looking closely at the base sequence in our DNA code. When the DNA bases are changed, the gene may function differently. Most variants are harmless and in fact make you unique. Some gene variants may even be beneficial, and can offer a benefit during evolution. For example, a variant could potentially increase our natural defense against some viruses. On the other hand, some gene variants can lead to genetic disorders, such as SDS. Based on their capabilities of causing disorders, variants are classified into five major categories: Pathogenic Likely pathogenic Variants of uncertain significance (VUS) Likely benign Benign When looking at a particular variant, it can be tricky to figure out into which category it belongs. The determination is usually made by testing laboratories based on various types of evidence. For example, if many patients with a particular disorder all have the same "variant" or "mutation", and the protein's function is well known, then researchers make the determination that is is pathogenic. This information is then available to the testing laboratories through specialized online databases, and scientific publications. If such information is not established for a particular variant, computer modeling and comparison of the sequence of the same gene in other organisms can provide good evidence. For example, if a change is detected in a region of the protein that is known to be critical for its function, then the variant may be "likely pathogenic". And/or if the change is in a region of the gene that is the same across multiple species, then that suggests that it is critical for the protein's function, and again is "likely pathogenic". Unfortunately, more often then not, the above mentioned evidence is not present, and therefore scientist and clinicians don't have enough information to determine the significance of the variant. In those frequent cases, the variant would be called a VUS (variant of uncertain significance). The best way to determine whether a variant is significant would be to develop a functional assay to determine whether the cellular process in which the protein is involved is disrupted; or whether some other key phenotype is affected. Another term for these measures are biomarkers, and as explained in a previous snapshots issue, they are incredibly important for therapy development as well. In the case of SDS, if there was an easy, validated assay to measure ribosome assembly or other markers, that would be a great way to tell whether a VUS in SBDS has any significance. We are currently working with our partners on develop biomarkers for this and other reasons. Have you or your loved-one received VUSs in your genetic report? It’s important to work closely with an experienced SDS specialist or geneticist to help you understand what the VUS might mean for you or your family. Not all variants in SBDS or the other SDS genes means SDS. If a child is diagnosed with a VUS, it is helpful to have mom and dad tested as well to see if either of them have the same variant. If a parent shares a variant with their child, but the parent does not have symptoms that the child is experiencing, it is less likely that the VUS is pathogenic (or it would have likely affected the parent). Every family with SDS as a potential diagnosis on their genetic report should reach out to an SDS specialist and enroll in a Registry and/or Natural History Study that covers your geographical area. Find a list, here: https://www.sdsalliance.org/sds-registries. Contact us at connect@SDSAlliance.org if you need additional guidance. Why do I need to know whether I or my loved-one has "genetic" SDS? As mentioned above, over 90% of SDS patients have mutations in both copies of their SBDS gene. This group of patients have been most thoroughly studies, as this is where most data is available. As most of us are keenly aware, SDS in these patients causes a high risk of MDS/AML (leukemia). However, this risk has NOT been established in SDS patients without a known genetic cause (often referred to as "clinical" SDS patients, or SDS-like). A recent example of some amazing research was published last year by Dr. Shimamura's group, where acquired / somatic mutations were measured and summarized. We can cover the article in more detail another time. The article is available for download, here: https://pubmed.ncbi.nlm.nih.gov/33637765/ As we learn more over time, it is very possible that different types of SDS patients will benefit from different types of monitoring and treatment options. Perhaps one group will need frequent monitoring for leukemic transformation and clonal hematopoiesis, while the others may not need monitoring that often. One group may benefit from some types of treatment options, while others may need other options. The natural history of the different groups may be different as well, and could have implications on how clinical trials and comparator arms are structured. Regardless of what category of SDS you or your loved-one falls into, please consider participating in research, be it in registries or clinical trials in the future. Find a list, here: https://www.sdsalliance.org/sds-registries. Do you enjoy the SDS & Science Snapshots? You can Sign up by using the button on top right of this post:

The last day of February is Rare Disease Day, but for us - rare disease families and advocates - every day is rare disease day. But no worries! We just got extra help! Please meet Ribo & Somi, the ribosome superheroes. They are our new mascots, with the mission to #CureSDS, and teaching the kids in our community about SDS science and advocacy in a fun and approachable way. They are launching into action with two new resources for kids: The 2022 Coloring Calendar full of information about all things SDS, and a new page on our website dedicated to kid friendly information and resources. Check out: www.SDSAlliance.org/kids-corner Have fun learning and advocating! (P.S. new T-shirts and other fun themed items coming soon. Stay tuned.) Update: New languages and formats for the calendar have been added and can be downloaded from www.SDSAlliance.org/kids-corner!

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