In this issue: Q&A with an SDS Advocate: What were they doing on Rare Disease Day? (¡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! Spring into Action: Joyce's Rare Disease Day Experience Every year, on the last day of February, the international Rare Disease Community comes together to raise awareness about important policy and other issues related to rare disease. For us, every day is Rare Disease Day. Check out our updated Rare Disease Day website. Rare Disease Day, for us, is a launch pad for our "Spring into Action" campaign, with which we amplify the patient voice in SDS in order to improve patients' lives, be it through more focused, impactful research, community support, or advocacy. Over the next few weeks and months, we will highlight multiple efforts on how the SDS community springs into action, starting with how our community leveraged Rare Disease Day events to learn and make progress. Today, we bring you an interview with Joyce, a young advocate living with SDS, highlighting her Rare Disease Day experience. You can learn more about Joyce’s story of living with SDS on the Rare Disease Day website where she is featured as a hero or in this 60 Seconds of RARE video published by the RARE Revolutions Magazine. What event(s) did you participate in for Rare Disease Day and what was your motivation to participate? Joyce: On Rare Disease Day in 2024, I participated in the Rare Disease Legislative Advocates’ Annual Rare Disease Week on Capitol Hill. Over four days we attended conferences, caucus briefings, and discussions. On February 27th, everyone had meetings with their state senate offices and representatives to share their story and introduce legislation to help them in their journey. I was motivated to participate in this event not only because of my advocacy experience and public speaking skills, but also because I wanted to share my story to help assist and guide the government into making decisions that would benefit the rare disease community. I used my experiences and knowledge to my advantage to guide the minds of those in Congress to sign-off on key legislation that would impact the rare disease community. What was your most memorable moment from Rare Disease Day? My most memorable moment from Rare Disease Week was meeting others with rare diseases or connecting with rare diseases and advocating together. It was such an empowering moment to be able to connect with others who have experienced similar journeys – being together in one room to advocate for similar goals. We all were encouraging and standing with each other during our meetings and events to motivate ourselves and the people around us. I very much enjoyed being able to speak up about some issues involving the rare disease community and some possible legislation that would impact the SDS community. Did you learn anything new or gain any insights from your participation in Rare Disease Day events? I learned a lot this year on Rare Disease Week. I learned how to gain a stronger understanding of how to tell my story, and what details to share when speaking with government officials. I learned how I can incorporate my experience and journey with SDS into advocating for certain bills for the rare disease community as a whole. I gained insight from fellow peers, advocates, and leaders in the rare disease community about the diagnostic odyssey of rare disease patients and what each individual is doing to help us as a community. I learned how to transform my public speaking skills into a motivational day full of business and fun. Plus a fun little perk of attending this event is that I learned how to navigate my way through the US House of Representatives and Senate buildings through underground tunnels. How do you plan to continue advocating for SDS and other rare diseases beyond Rare Disease Day? I plan to continue to be an active member of the Rare Disease Legislative Advocates this year, speaking out for legislation for the rare disease community. This year I plan to be an active Young Adult Rare Representative as I enter my 16th year of life. I plan to continue to use my experience of living with a rare genetic disorder to further expand the knowledge of those around me about SDS and the problems surrounding our community. By using my story, I can have solid backing for my proposals to the congressmen and women, giving them a personal connection to the legislation. I also plan to continue to post on my SDS Instagram account @cure.sds, to provide information on the disease and what daily life looks like. What advice would you give to others who are interested in getting involved in advocacy efforts for Rare Disease? The advice I give to others is always to use their past experiences and traumas to their advantage in the field of advocacy. Use your insight and knowledge of living with or caring for someone with a rare condition to be able to speak up against the issues in the rare disease community. I always tell people they should not fear their disease and instead make it a part of them. In advocacy work, it is key to embrace your disorder to truly be able to speak out and stand up for what is right. By using your story, you can catch the eyes of people who may have never heard of your disorder and are willing to help. If you are just entering into the advocacy space, I recommend starting small, creating a social media platform to raise awareness and give insight into the common problems and daily life of living with a rare disorder. Never stop because something goes wrong, use that negative event as further inspiration to keep thriving as an advocate and as a human being. Not everything is going to go your way all the time, there will be some bumps in the road, so turn that negativity into strength. On behalf of our team at SDS Alliance - Joyce, we thank you for your hard work, dedication, and passionate advocacy for the SDS community on Rare Disease Day and everyday! We are grateful to have you as a member of our community and can't wait to see how you transform the lives of so many living with a rare disease. __________________________________________________________________________________ Check out our new SDS infographics (available in English and Spanish/Español)! __________________________________________________________________________________ If you’re interested in viewing some of this year’s Rare Disease Day events, many of them were recorded and are now available to stream online: The White House: Rare Disease Forum Broad Institute of MIT and Harvard: Rare Disease Day 2024: Climbing Ladders to Cures in Rare Disease Research National Institutes of Health (NIH): Rare Disease Day Event US Food and Drug Administration (FDA): FDA's Rare Disease Day 2024—Dedicated to Patients and Providers __________________________________________________________________________________ Actúe: la experiencia del Día de las Enfermedades Raras de Joyce En este número: Preguntas y respuestas con un defensor de SDS: ¿Qué estaban haciendo el Día de las Enfermedades Raras? Cada año, en el último día de febrero, la comunidad internacional de enfermedades raras se reúne para crear conciencia sobre políticas importantes y otras cuestiones relacionadas con las enfermedades raras. Para nosotros, cada día es un día de Enfermedad Rara. Para nosotros, el Día de las Enfermedades Raras es una plataforma de lanzamiento para nuestra campaña "Actúe en primavera", con la que amplificamos la voz de los pacientes en SDS para mejorar sus vidas, ya sea a través de investigaciones más enfocadas e impactantes, apoyo comunitario o abogacía. Durante las próximas semanas y meses, destacaremos múltiples esfuerzos. Hoy les traemos un resumen de cómo nuestro equipo aprovechó los eventos del Día de las Enfermedades Raras para aprender y progresar. Le preguntamos a Joyce, una joven defensora que vive con SDS, sobre su experiencia en el Día de las Enfermedades Raras. Puede obtener más información sobre la historia de Joyce sobre cómo vivir con SDS en el sitio web del Día de las Enfermedades Raras, donde aparece como una heroína o en este video de 60 Seconds of RARE publicado por la revista RARE Revolutions. ¿En qué eventos participó para el Día de las Enfermedades Raras y cuál fue su motivación para participar? Joyce: En el Día de las Enfermedades Raras de 2024, participé en la Semana Anual de Enfermedades Raras de los Defensores Legislativos de Enfermedades Raras en Capitol Hill. Durante cuatro días asistimos a conferencias, reuniones informativas y discusiones. El 27 de febrero, todos se reunieron con las oficinas y representantes del senado estatal para compartir su historia y presentar legislación que los ayude en su viaje. Me motivó a participar en este evento no solo por mi experiencia en defensa de derechos y mis habilidades para hablar en público, sino también porque quería compartir mi historia para ayudar y guiar al gobierno en la toma de decisiones que beneficiarían a la comunidad de enfermedades raras. Utilicé mis experiencias y conocimientos a mi favor para guiar las mentes de los miembros del Congreso para aprobar una legislación clave que afectaría a la comunidad de enfermedades raras. ¿Cuál fue tu momento más memorable del Día de las Enfermedades Raras? Mi momento más memorable de la Semana de las Enfermedades Raras fue conocer a otras personas con enfermedades raras o conectarme con enfermedades raras y abogar juntos. Fue un momento muy enriquecedor poder conectarme con otras personas que han experimentado viajes similares: estar juntos en una sala para abogar por objetivos similares. Todos nos animamos y nos apoyamos unos a otros durante nuestras reuniones y eventos para motivarnos a nosotros mismos y a las personas que nos rodean. Disfruté mucho poder hablar sobre algunos temas que involucran a la comunidad de enfermedades raras y algunas posibles leyes que afectarían a la comunidad SDS. ¿Aprendió algo nuevo u obtuvo alguna información a partir de su participación en los eventos del Día de las Enfermedades Raras? Aprendí mucho este año en la Semana de las Enfermedades Raras. Aprendí a comprender mejor cómo contar mi historia y qué detalles compartir al hablar con funcionarios del gobierno. Aprendí cómo puedo incorporar mi experiencia y mi trayectoria con SDS para defender ciertos proyectos de ley para la comunidad de enfermedades raras en su conjunto. Obtuve información de colegas, defensores y líderes de la comunidad de enfermedades raras sobre la odisea diagnóstica de los pacientes con enfermedades raras y lo que cada individuo está haciendo para ayudarnos como comunidad. Aprendí cómo transformar mis habilidades para hablar en público en un día motivador lleno de negocios y diversión. Además, una pequeña ventaja divertida de asistir a este evento es que aprendí a navegar a través de los edificios de la Cámara de Representantes y del Senado de los Estados Unidos a través de túneles subterráneos. ¿Cómo planea continuar abogando por el SDS y otras enfermedades raras más allá del Día de las Enfermedades Raras? Planeo seguir siendo un miembro activo de los Defensores Legislativos de Enfermedades Raras este año, defendiendo la legislación para la comunidad de enfermedades raras. Este año planeo ser un Representante Raro de Adultos Jóvenes activa al cumplir 16 años de vida. Planeo seguir utilizando mi experiencia de vivir con un trastorno genético poco común para ampliar aún más el conocimiento de quienes me rodean sobre el SDS y los problemas que rodean a nuestra comunidad. Al utilizar mi historia, puedo tener un respaldo sólido para mis propuestas a los congresistas, brindándoles una conexión personal con la legislación. También planeo seguir publicando en mi cuenta de Instagram de SDS @cure.sds, para brindar información sobre la enfermedad y cómo es la vida diaria. ¿Qué consejo le daría a otras personas interesadas en participar en esfuerzos de defensa de las enfermedades raras? El consejo que doy a los demás es siempre que utilicen sus experiencias y traumas pasados ​​a su favor en el campo de la defensa. Utilice su visión y conocimiento sobre cómo vivir con alguien con una enfermedad rara o cuidar de ella para poder hablar en contra de los problemas de la comunidad de enfermedades raras. Siempre les digo a las personas que no deben temer a su enfermedad y, en cambio, hacerla parte de ellos. En el trabajo de promoción, es clave aceptar su trastorno para poder verdaderamente hablar y defender lo que es correcto. Al utilizar su historia, puede captar la atención de personas que tal vez nunca hayan oído hablar de su trastorno y estén dispuestas a ayudar. Si recién está ingresando al espacio de la defensa, le recomiendo comenzar poco a poco, creando una plataforma de redes sociales para crear conciencia y brindar información sobre los problemas comunes y la vida diaria de vivir con una enfermedad rara. Nunca te detengas porque algo sale mal, utiliza ese evento negativo como inspiración adicional para seguir prosperando como defensor y como ser humano. No todo va a salir como quieres todo el tiempo, habrá algunos obstáculos en el camino, así que convierte esa negatividad en fuerza. En nombre de nuestro equipo en SDS Alliance - Joyce, le agradecemos su arduo trabajo, dedicación y defensa apasionada de la comunidad SDS en el Día de las Enfermedades Raras y todos los días. Estamos agradecidos de tenerla como miembro de nuestra comunidad y estamos ansiosos por ver cómo transforma las vidas de tantas personas que viven con una enfermedad rara. __________________________________________________________________________________ ¡Mira nuestras nuevas infografías sobre SDS (disponibles en inglés y español)! __________________________________________________________________________________ Do you enjoy the SDS & Science Snapshots? You can Sign up by using the button on the top right of this post:

"My journey as a mother of a child with a rare disease began when I had my 20-week ultrasound while pregnant with my son Alex", shares mom Paula. Paula shared their story beautifully in a detailed blog on the "Extra Lucky Moms" blog. Check it out! Below, with Paula's permission, we are sharing some short excerpts. "When Alex was five months old, he caught a cold. I watched as his little chest keep rising and falling. Then I could see his ribs and collar bone as he tried to suck in air. Something was wrong. His breathing was extremely labored. I rushed him to the emergency room. They immediately took him to a triage room. While they were examining him, I watched as my baby stopped breathing completely. It felt like time stopped, and it may have only lasted about 20 seconds in reality, but it was enough time for his entire body to turn this awful dark purple color. From head to toe, he was the color of an eggplant. I remember looking at the nurse and finally saying “Do something, he’s not breathing!” "After Alex’s ankle surgery [for a serious infection], one of the doctors recommended we see a genetic specialist. She was the first doctor to look at his entire medical history and suggest that there might be something that ties all of his seemingly random medical events together. So, we made an appointment with another specialist and more tests were done. Alex kept getting sick, coming down with colds, having labored breathing, and having to go to the emergency room. We were at the emergency room or at a doctor’s office almost every two to four weeks. We were hoping for some answers. While we waited for his genetic test results to come back in, our pediatrician noticed that Alex was flapping his hands a lot at one of his appointments. He would also occasionally walk on his toes. She started to ask me questions about his speech and his vocabulary. I shared this his vocabulary was limited but I attributed that to all the time he has been spending in the hospital. Then she hit me with something I was not expecting. She recommended we see a behavioral pediatrician to have him evaluated for Autism Spectrum Disorder. He did so many things well that once again, I naively believed that this would simply be an evaluation to check this off the list and rule it out. So, another appointment with another specialist was made. Then came the two weeks in October of 2020 that I will never forget. First, I received the call from the genetics office. They had Alex’s test results in and confirmed that he had a very rare genetic disorder called Shwachman Diamond Syndrome. All the person from the genetics office could tell me about it was that it is a bone marrow disorder and that I needed to make a follow up appointment with the hematology and oncology team at the children’s hospital. I had so many questions but she could not answer any of them because it was not her specialty. Her job on that call was just to deliver the diagnosis, not provide any answers. So like anyone would do, I went to the internet. And this is when my heart broke again. Shwachman Diamond Syndrome is a bone marrow disease that impacts every single system of the body." Read the full story on the "Extra Lucky Moms" blog, here.

In this issue: What is a pseudogene and why does it matter? Important genetic testing considerations 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! SBDS pseudogene complicates receiving an accurate genetic diagnosis for SDS Long diagnostic journeys, otherwise known as the diagnostic odyssey, are not uncommon across rare diseases, specifically SDS. The barriers to diagnosis often vary but can include limited access to providers knowledgeable about SDS, nonspecific initial SDS symptoms that can overlap with other conditions (e.g., pancreatic insufficiency can also be seen in patients with cystic fibrosis), and difficulties accessing genetic testing (see our Science Snapshot from 2023-02-05). However, even once genetic testing has been completed, some individuals with SDS face additional barriers to receiving a genetic diagnosis due to false-negative or false-positive results, again prolonging the diagnostic odyssey. In the article we are highlighting this week, inaccuracies in data analysis and special considerations for genetic testing for SDS, and the SBDS gene more specifically, are discussed. The authors describe a 3-month-old female in Korea with suspected SDS due to typical SDS symptoms (neutropenia, anemia, failure to thrive, decreased pancreatic enzymes, and elevated liver enzymes) who participated in genetic testing for SDS. Genetic testing revealed increased levels of one variant (i.e., mutation) commonly seen in individuals with SDS, but the proportion of this variant in comparison to other genetic changes was still lower than expected. This prompted the authors to complete a different type of genetic testing, called Sanger sequencing, which analyzes the SBDS gene one genetic position at a time. Sanger sequencing not only identified the previously detected variant, but it also detected a second genetic variant which is another variant commonly seen in individuals with SDS. Identification of this second variant in SBDS confirmed this individual’s diagnosis of SDS. But why was this second genetic variant not identified using the first method of genetic testing? Our genetic information, or DNA, collectively known as the genome, is a collection of over three billion letters (i.e., bases, A, T, G, or C) in a very specific sequence to form genes. However, less than 1% of these genes are used as instructions for building proteins (i.e., protein-coding genes). The bases in the remaining 99% of our genome contain important regulatory regions, protective DNA regions, and pseudogenes which can be compared to a “genomic fossil.” As a result of evolution, these pseudogenes were once considered to be functional protein-coding genes but are now inactive and obsolete genes in our genomic information today. These pseudogenes are highly similar in their sequence to that of their functional, protein-coding genes’ counterparts, and depending on the level of similarity (i.e., homology), can be difficult to differentiate between when performing genetic sequencing and data analysis. Some of the defects in pseudogenes that result in their inactivation are outlined in the image below. The SBDS gene, the gene mutated in most individuals with SDS, has a pseudogene, or genomic fossil, in another part of the genome. Depending on the sequencing method, protein-coding gene sequences can be switched with pseudogenes, such as SBDS, resulting in a false-positive or false-negative result. This YouTube video, published by PBS, explores pseudogenes through a historical lens and shares other real-life examples of pseudogenes and the important role they used to play. Compared to NGS methods, Sanger sequencing reads/identifies one genetic base at a time without fragmenting the original sequence. As a result, there is no re-alignment necessary, dramatically reducing the risk of inaccurate genetic testing results. Sanger sequencing is considered the gold standard of genetic testing for this reason, but is more time-consuming, labor intensive in its preparation, and expensive in comparison to NGS methods. In this week’s article, Sanger sequencing was performed as a second method of genetic testing and successfully identified two variants in the SBDS gene, confirming an SDS diagnosis for the 3-month-old female. The authors from this week’s article encourage readers to acknowledge “the risk of erroneous diagnosis of disease-causing genes with pseudogenes when performing short-read NGS.” Another report from April 2020, written by Yamada et al. (PMID: 32412173), discusses a similar experience with short-read NGS in multiple individuals with SDS and advocates for the use of other genetic testing methods (e.g., Sanger sequencing or long-read sequencing) to identify and/or confirm SBDS variants. Accurate genetic diagnoses of SDS are important for implementing appropriate screening protocols and treatment regimens. For those with negative genetic testing or one SBDS variant detected using short-read NGS and a clinical presentation suspicious for SDS, follow-up genetic testing could be considered using Sanger sequencing, long-read NGS sequencing, deletion analyses, and/or RNA sequencing to confirm the presence (or absence) of another variant in SBDS. __________________________________________________________________________________ For more information regarding pseudogenes, you can refer to the Talking Glossary of Genomic and Genetic Terms on the National Human Genome Research Institute’s website or to this article published by Blueprint Genetics, a genetic testing company. Variant Allele Frequency of Pseudogene-Related Variants in Short-read Next-Generation Sequencing Data May Mislead Genetic Diagnosis: A Case of Shwachman-Diamond Syndrome. Lee H, Lee JA, Lee H, Lee JS, Ko JM, Kim MJ, Seong MW. Ann Lab Med. 2023 Nov 1;43(6):638-641. doi: 10.3343/alm.2023.43.6.638. PMID: 37387500 Do you enjoy the SDS & Science Snapshots? You can Sign up by using the button on the top right of this post:

In Loving Memory Steve, Niamh's beloved husband, shares Niamh's story. On Thursday 11th August 2022, our world changed forever. This is the day our beloved Niamh passed away from a short illness caused by a bacterial infection which proved tragically fatal. On the Tuesday of that week she was in great form, we'd been out on a sunny day enjoying a few drinks in a beer garden and nice Chinese meal. On the Wednesday she fell ill and we took her to hospital, by the Thursday she had left us. The infection was called necrotising fasciitis, its a rare but dangerous bacterial infection. Niamh had chronic neutropenia which meant she was more likely to catch this, and sadly less able to fight it due to having a very weak immune system. Niamh had only found out within a year before she passed away of her diagnosis of SDS, which led to her neutropenia condition. Niamh actually took comfort and encouragement from her SDS diagnosis, it helped explain some of why she had suffered since a baby, she felt a new additional support from the online SDS community, and it gave her hope to find a way to live a more healthy life through leaning more about the condition. Cruelly ironic, we had an appointment with her consultant to learn more about SDS on the day she died. Niamh was in and out of hospital as a baby, regularly sick throughout her childhood, and barely a month went by as an adult without seeing one of her numerous medical consultants for the several conditions she was living with. Sadly this is the reality of living with SDS. She also suffered significant loss emotionally, in particular her beloved mother Mary passed away whilst Niamh was still in her teens. But despite all of this, Niamh was the loveliest, bubbliest, most cheerful, caring, generous and silliest person you could ever have the fortune to meet. Anyone that knew her said she would light up a room when she entered. Born and bred in Dublin, Ireland, she came from a large & loving Irish family, and she was extremely close to all from the close & extended family. She also made huge efforts to always spend time with her many friends, she was loyal and great company to all. A special mention to her best friend Karen, they knew each other since school and were like sisters, supporting each other through good times and bad. Niamh was well known in her community, since we moved into the neighbourhood 10 years ago she set upon herself to organise the first ever street party here (and also the 2nd and 3rd!) before covid put a halt on those. As a stop gap she dragged her karaoke machine onto the road and we played socially distanced bingo to keep everyone entertained through difficult isolating times. And she never stopped trying to get involved with local people and getting people together, no better shown than when within the year before she died she founded the Dublin 7 Women's Shed, which is now going from strength to strength with well over 100 members. Some of Niamh's very best friends though did not have 2 legs but 4. She was a lover of all animals, and in particular dogs. Whilst not working during covid Niamh minded several local dogs on a part time basis and took great joy out of this, as did all the doggies! And whilst we never had children, we did have our own little dog Basil, a Cavalier King Charles. Sadly Basil passed away 2 weeks after Niamh, he was 14 years old, and just as heart broken as everybody else, he loved his mammy very much. I met Niamh backpacking around New Zealand in 2006. Niamh loved a holiday whether it was exploring a new place, travelling round beautiful Ireland with Basil, or soaking up some rays in the sun. She said her favourite trip was when we went to Cuba, we did this on a group tour and typical of Niamh, she was the life and soul of the group and quickly nicknamed the Daiquiri Queen. Niamh loved to be busy when she was able, and also loved the outdoors, so her recent taking up of gardening suited her well. Her specialities were growing of spuds, tomatoes, sweetpea and sunflowers. Niamh loved to laugh, whether it be cheesy puns or sticking googly eyes everywhere. We'd regularly attend comedy gigs together. She had a daft and silly sense of humour, her giggle, often starting as a cackle and sometimes becoming so unstoppable that it almost caused her to choke and quickly grab her inhaler, was unique, unmissable and infectious, and full of joy. Niamh loved music and going to gigs, especially outdoor festivals. She always had a fun loving 60s/70s vibe and would have fit in well when the Beatles and Donovan were banging out the tunes. She could dance around to cheesy pop, and head-bang to something more rocky and punky. Her favourite band were Ash, and their song Shining Light we've since adopted as its such a beautiful description of Niamh, our shining light. Another band we got into recently are called Dream Wife. And that for me is the perfect description of Niamh. She was loving and caring. She was supportive and understanding. She was smart and funny. She was brave and courageous. She was great fun, the best craic you can imagine. She was beautiful from head to toe. She was my best friend and my soul mate. Life is unbelievable tough now without Niamh by our side. She was loved by so many, and we were all lucky to be loved by Niamh. Niamh was always one who saw the best of people and the positives in situations wherever they existed. So in that vain, along with some close family and friends, we'll be participating in a remembrance run this November, doing this both in Niamh's memory and also to raise funds for the SDS Alliance. https://www.dublinlive.ie/news/dublin-news/my-wife-died-rare-disease-27714675 https://www.gofundme.com/f/in-memory-of-niamh-curesds Niamh Lynch-Livsey, aged 44 years, forever young, always loved, always in our hearts.

In this issue: Recap of publication on Ataluren to pave the path for clinical trials. Learn more about how it works in this post. Welcome to our timely updates on all things SDS, Science, and Advocacy. We bring you a digest of recent scientific publications, conferences, and other newsworthy content - all relevant to SDS - with links to more details and learning opportunities. Are you interested in anything specific? Did we miss something? Let us know. Email genetics@SDSAlliance.org or message us on Facebook! This is all for you! An update on the development of Ataluren, a therapeutic approach targeting the c.183_184TA>CT mutation in the SBDS gene Over the past few years, important research has been ongoing in Dr. Valentino Bezzerri and Dr. Marco Cipolli’s laboratory in Italy to investigate the use of Ataluren to treat individuals with SDS. We previously wrote about this work, including a detailed summary by Dr. Bezzerri in a SDS & Science Snapshot edition from May 2022 and October 2023. This week, the publication has finally hit the shelves and is now available for free online. It expands the pre-clinical laboratory based research to solidify the rationale to enable clinical trials for Ataluren for a subset of SDS patient. The authors show, that Ataluren improved ribosome assembly and total protein synthesis in SDS-patient-derived cells in the lab Restored myelopoiesis in myeloid progenitors in the lab Improved neutrophil chemotaxis in an experimental model Reduced neutrophil dysplastic markers in the lab. Restored full-length SBDS protein production in osteoblasts (bone producing cells) donated by patients, suggesting that its beneficial role may go beyond the blood producing stem cells. The authors summarize: "Altogether, our results strengthened the rationale for a Phase I/II clinical trial of ataluren in SDS patients who harbour the nonsense mutation". Dr. Bezzerri also shared his work at the 2023 SDS POPS summit in May and joined us for a lively discussion at our first ever Ask-an-Expert Community Chat. It was fantastic. Check out the recording, below. As previous highlighted, the group tested the effect of Ataluren in the laboratory on cells of individuals with SDS who harbor the c.183_184TA>CT mutation in their SBDS gene. These preclinical studies showed: Improved SBDS protein levels and improved ribosome assembly and total protein synthesis; Reduced the elevated levels of p53 protein, which is found in excess in SDS tissues; and Improved migration of neutrophils, important cells in the immune system frequently reduced in individuals with SDS. These results are promising for Ataluren and its use as a "personalized medicine" approach for treating SDS patients carrying nonsense variants, such as c.183_184TA>CT. These preclinical results support the idea of developing of a Phase I/II clinical trial in the future for Ataluren in SDS patients who have a nonsense mutation. The SDS Alliance team will remain in communication with the SDS community about these trials when/if they become available. Be sure to sign up for updates! The figure below summarizes the findings published in the current article. The top of the figure shows what normally happens in SDS cells that harbor a nonsense variant. The bottom panel shows the mechanism of Ataluren and the improvements it makes on the cellular environment. What is the significance of the c.183_184TA>CT mutation in SBDS gene? A large percentage of SDS patients carry the variant (i.e., mutation), c.183_184TA>CT, in addition to the most common “splice site” variant. For instance, the c.183_184TA>CT variant is present in more than half of SDS patients. This genetic change leads to the generation of a premature stop in building the SBDS protein, similar to inserting a period in the middle of a sentence. These types of variants, known as nonsense variants, generally result in unstable protein intermediates and are rapidly degraded in the cell or produce a protein that has lost its function. What is Ataluren? Ataluren (PTC124) was launched in 2007 by PTC Therapeutics (NJ, USA), which promotes careful attention to “incorrect punctuation” in cells (e.g., an extra period in the middle of a sentence). This attention allows for more selective synthesis of proteins with normal structure (i.e., proteins without the extra period in the middle of the sentence). Furthermore, Ataluren has shown less toxicity and better safety than other drugs used for similar purposes. The use of Ataluren as a potential therapeutic agent for genetic disorders has been proposed for the treatment of Duchenne Muscular Dystrophy (DMD) and Cystic Fibrosis (CF). Most importantly, Ataluren has been approved for the treatment of DMD in Europe (but not in the US). Data from clinical trials showed that chronic Ataluren treatment is beneficial to DMD patients undergoing standard care, because it delays the progression of ambulation impairment and the worsening of pulmonary and cardiac functions. Interestingly, clinical studies revealed that the best results are observed in younger individuals, suggesting major benefits of early ataluren administration. Why is Ataluren not widely used? Despite promising pre-clinical results, Ataluren unfortunately failed in clinical studies for CF and was therefore discontinued. This early work suggested there may be highly variable clinical benefits in using Ataluren to treat individuals with CF. Because of such variable levels of effectiveness of Ataluren, it is important to perform extensive preclinical testing using cells in the laboratory, such as the recent work published by Cipolli et al., before trying Ataluren in people with SDS in clinical trials. Find additional information about Ataluren and its treatment of individuals with DMD by watching this YouTube video. Ataluren improves myelopoiesis and neutrophil chemotaxis by restoring ribosome biogenesis and reducing p53 levels in Shwachman-Diamond syndrome cells. Cipolli M, Boni C, Penzo M, Villa I, Bolamperti S, Baldisseri E, Frattini A, Porta G, Api M, Selicato N, Roccia P, Pollutri D, Marinelli Busilacchi E, Poloni A, Caporelli N, D'Amico G, Pegoraro A, Cesaro S, Oyarbide U, Vella A, Lippi G, Corey SJ, Valli R, Polini A, Bezzerri V.Br J Haematol. 2024 Jan;204(1):292-305. doi: 10.1111/bjh.19134. Epub 2023 Oct 24. PMID: 37876306 Do you enjoy the SDS & Science Snapshots? 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In this issue: Rare Disease Day is around the corner! How can I get involved? Welcome to our timely updates on all things SDS, Science, and Advocacy. We bring you a digest of recent scientific publications, conferences, and other newsworthy content - all relevant to SDS - with links to more details and learning opportunities. Are you interested in anything specific? Did we miss something? Let us know. Email genetics@SDSAlliance.org or message us on Facebook! This is all for you! Share Your Colors on Rare Disease Day! WHAT IS RARE DISEASE DAY? Rare Disease Day is the official international awareness-raising campaign for rare diseases, observed annually on the last day of February. The primary goal of this campaign is to increase awareness among the general public and decision-makers about rare diseases and their influence on the lives of families living with these conditions. Rare Disease Day was launched by EURORDIS Rare Diseases Europe and its Council of National Alliances in 2008. EURORDIS continues to lead the international campaign with a global patient community. Patient organizations from North America joined in 2009, followed by all continents by 2010. National Alliances, such as the Nation Organization for Rare Disorders (NORD) in the United States, ensure Rare Disease Day coordination at a national level, collaborating with local patient organizations and often organizing national events targeting policymakers. The number of participating countries has grown annually, with thousands of events now occurring on all continents in or around February. Since 2008, events have been held in over 100 countries. Fun Fact: You can virtually attend the NIH Rare Disease Day Event with SDS Alliance! Our Genetics Project Manager, Ashley Thompson, MS, CGC will be attending this event in-person to represent SDS Alliance and the SDS community this coming week. Stay tuned for our Snapshot next week for updates on these events and others! CELEBRATE THE UNIQUENESS OF BEING RARE With over 300 million people globally living with a rare disease (and an estimated 5000 individuals with SDS in the US and Europe), we join hands with you across borders and amidst the 6000+ rare diseases to advocate for equitable access to diagnosis, treatment, care, and social opportunities. The key message for Rare Disease Day 2024 is SHARE YOUR COLORS! Here are some ways to get involved in this year's campaign: 1.GET INVOLVED ON SOCIAL MEDIA Share your Rare Disease Day event videos - such as the timeless video we created for SDS, below - and photos on social media using #RareDiseaseDay and tag @rarediseaseday. You can also express your support for those living with rare diseases in your community by sharing a photo with painted hands on social media. Explore the Rare Disease Day website for downloads including images, profile picture frames, Instagram filters, and Zoom backgrounds, and more that you can use on social media! Use crucial rare disease statistics to convey that while each disease may be rare, collectively, they impact a vast number of people. 300 million people worldwide live with a rare disease. There are over 6000 different rare diseases. 72% of rare diseases are genetic. 70% of these genetic rare diseases begin in childhood. There are an estimated 5000 individuals living with SDS in the US and Europe, and many more are undiagnosed! 2. ORGANIZE AN EVENT! Every year, thousands of events across over 100 countries commemorate Rare Disease Day. Most events will be online, allowing people worldwide to participate. Plan an online event in or around February for Rare Disease Day to heighten awareness of rare diseases in your community. Here are some successful ideas from global organizers: Illuminate your home for Rare Disease Day: see the Light Up for Rare Toolkit for more information. Raise awareness on Facebook and Instagram Live, and invite your friends. Hold an art, photography, or essay-writing competition. Organize a walk. Plan a sporting event. Present your story to your local authorities. 3. BECOME A FRIEND Become a Rare Disease Day friend to showcase your organization or company’s support for the campaign! Simply fill in your details to create a profile page on the Rare Disease Day website. This will display your commitment to supporting people living with a rare disease. 4. TELL YOUR STORY! Raise awareness about rare diseases and their impact on people’s lives by sharing your personal experience of living with SDS or caring for someone who does. Submit your written or video testimony on the Rare Disease Day website and explore stories already shared by others! 5. TAKE ACTION LOCALLY In addition to organizing events, you can act locally in your country, region, or area to raise awareness of rare diseases! On Rare Disease Day, we advocate for equity for people living with a rare disease worldwide. CONTACT THE PRESS Reach out to local or regional newspapers and radio stations to cover your Rare Disease Day event. Send out a press release to your area’s media, highlighting the issues most crucial to rare disease patients in your country. Watch the webinar ‘How to Use Rare Disease Day to Advance Your Advocacy Objectives’ to learn the basics! GET POLITICAL Write to key decision-makers about the pressing issues facing rare disease patients in your country, urging them to prioritize rare diseases! Advocate to policymakers for equitable access to diagnosis, treatment, care, and social opportunities for those living with a rare disease. For guidance on advocating for rare diseases within Universal Health Coverage, refer to the Rare Disease Day Equity Toolkit. Invite politicians to your organization, to an event you’re hosting, or to a rare disease research lab. If you live in Europe, encourage your MEP to join the Parliamentary Advocates for Rare Diseases Network. If you live in the United States, register for Rare Disease Week on Capitol Hill hosted by the Rare Disease Legislative Advocates. 7. DOWNLOAD COMMUNICATION MATERIALS The official Rare Disease Day communication materials and logo are freely available for your Rare Disease Day events' promotion. Materials available in Mandarin, English, Arabic, Spanish, Portuguese, French, Hindi, and Russian. Also available for download: The official Rare Disease Day logo Website countdown Rare Disease Day style guide Fonts Webinar toolkits. If you, your friends, family, and colleagues take part in Rare Disease Day, don’t forget to share your photos from activities worldwide by uploading them to the Rare Disease Day website! We cannot wait to see how the SDS community lights up for rare this week! __________________________________________________________________________________ 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 matter in rare disease research and how can I get involved? Welcome to our timely updates on all things SDS, Science, and Advocacy. We bring you a digest of recent scientific publications, conferences, and other newsworthy content - all relevant to SDS - with links to more details and learning opportunities. Are you interested in anything specific? Did we miss something? Let us know. Email genetics@SDSAlliance.org or message us on Facebook! This is all for you! Embracing Diversity in Clinical Research: A Global Perspective As we honor Black History Month in the United States, it's essential to recognize the importance of diversity in clinical research and trials. Diversity in this context refers to including people from all walks of life – different races, ethnicities, backgrounds, and countries – in research studies. Why does this matter for those of us in the rare disease community? Embracing individuals from diverse backgrounds in clinical research is fundamental for advancing medical knowledge and improving healthcare outcomes worldwide. When clinical trials include people from diverse backgrounds, it helps scientists understand how treatments work for everyone. Every person is unique, and factors like where they live, their genes, and their culture can affect how they respond to treatments. By including a wide range of people in research, scientists, physicians, and other researchers can make sure that treatments are safe and effective for everyone, including those with rare diseases. Below is a video from a session at the 2023 Global Genes RARE Health Equity Forum: Understanding the Patient Perspective – How to Ensure Diverse Patient Participation in Clinical Trials and Research. In this session, the panelists discuss how patients can/should be on the front lines with their community ecosystem, and what that relationship should look like between community leaders and researchers. While we often hear about the need for diversity in terms of race and ethnicity, it's equally important to consider a broader global perspective. Rare diseases affect people all over the world, and what works for one person might not work for another. By involving researchers from different countries, we can learn from each other and find better treatments that work for everyone, no matter where they live. At Shwachman-Diamond Syndrome Alliance, we recognize that our community is diverse, encompassing individuals of various racial, ethnic, and cultural backgrounds from around the world, and we believe that everyone's voice deserves to be heard. By actively working together and engaging with our diverse global community, we aim to accelerate progress toward improved treatments and outcomes for individuals with SDS across the world. Together, let's continue to champion diversity and inclusivity in clinical research, ensuring that everyone has access to equitable and effective healthcare. __________________________________________________________________________________ The Rare Disease Diversity Coalition (RDDC) serves as a fantastic resource to the rare disease community – bringing together rare disease experts, patient organizations, health and diversity advocates, and industry leaders with a deep knowledge of the medical, industry, regulatory, and cultural challenges facing people of color with rare disease. __________________________________________________________________________________ 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! __________________________________________________________________________________ For more information about the importance of engaging a diverse global community in clinical research and trials, you can listen to these podcasts from Global Genes in addition to watching other sessions from the 2023 Global Genes RARE Health Equity Forum: Turning Words into Action: Equity, Diversity, and Inclusion in Rare Disease Addressing the Barriers to Patient Participation in Clinical Trials __________________________________________________________________________________ Do you enjoy the SDS & Science Snapshots? You can Sign up by using the button on the top right of this post:

Our SDS Story and what lead to Hero Kids in the Making Wg Williams, Elijah's dad, shares their story. "At only 15 months old, my son started undergoing lots of medical testing and treatments associated with his Shwachman-Diamond syndrome (SDS). He was only about 28 months old when his medical treatment-related anxiety started to become concerning. This became a separate new issue of his negative well-being. His anxiety would start to trigger in the parking lot of the doctor's office and only heightened from there. When he heard his named called in the waiting room he would start to cry in fear. At the time I was looking in the marketplace for the ideal childhood product that would inform, distract and reward my son in his participation in these procedures. I was looking for something in which the sugar-coat wasn’t so thick, and the distraction did not suggest that pain wouldn’t exist. I found no such children's product. I knew from having 11 nieces and nephews that regardless of what adults told children, they created fictitious monsters for their fears and imagery heroes overcome them. I wanted my son to see himself as a brave hero overcoming his reasonable fears associated with the pain and uncharted aspects of his medical tests and treatments. I then started to think that I could create such a tool myself. Being a big sci-fi fan and amateur writer, I remembered a quote I had learned; “Any sufficiently advanced technology is indistinguishable from magic”. This was from Arthur C. Clarke's “Profiles of the Future: An Inquiry into the Limits of the Possible”, a non-fiction book. I wanted my son to see himself as a brave hero overcoming his reasonable fears associated with the pain and uncharted aspects of his medical tests and treatments. I then started to think that I could create such a tool myself. I was thinking of a story that would be on a kid’s level of understanding and within their childhood interests. This would be a fun fantasy tale to grasp a child's imagination but also inspire bravery. I wanted an origin type story with cute magical animals that kids would adore. I wanted to include how these kids, who are actual heroes, could become their own hero kid in the making. I wanted a story easily understood by very young kids but still interesting and exciting to kids 10 years old. Children like him will always be heroes and modern medicine is truly magical. This story although fantasy, would also have to be an accurate kid’s self-help instruction manual for these medical procedures. The end result was this children’s picture book, Hero Kids in the Making!" About Wg Williams' children's picture book: Finally, a tool that prepares children for medical procedures in a fun way! This colorful storybook was especially created to help reduce childhood fears in their inevitable encounter with medical devices. "Hero Kids in the Making" is a children's picture book that redirects the imagination of a pediatric patient from a fearful perspective and towards a hero making tale that inspires bravery. This fun rhyming story turns medical procedures into cute, magical creatures. Instruments such as stethoscopes, syringes and imaging equipment are transformed into these magical animals, now in disguise. It's a fantasy hero making version of what the child will really experience during a doctor's or hospital visit. When a child familiar with this fantasy tale experiences medical procedures, they instantly become a hero character of the story themselves. The Coloring Book collaboration: When the SDS Alliance heard bout the book, the team fell in love with the story immediately. We started to think about how we could make it more accessible (easy to download and print) and more interactive for the kids. This is how the coloring book idea came to be. And luckily for the community, a 9-your-old child with SDS volunteered to create illustrations. The Hero Kids in the Making COLORING BOOK is now available on our kids' corner page. Check it out, today. To request printed copies and/or stickers, email us at connect@SDSAlliance.org

In Loving Memory Gabe passed away from AML following an unsuccessful stem cell transplantation, surrounded by his family. He leaves behind a sister, his parents, and a loving community of extended family and friends. His parents and community are so proud of all he has been able to achieve in his life. He graduated high school despite being sick, with a GPA of 4.7 and an Eagle Scout. His mom shares: Always trying to make his parents proud and always wanting to help. He wanted to be a biomedical engineer and change the world. If you would like to support his family, please consider donating to the GoFundMe page the family has set up at the start of his transplant journey: https://www.gofundme.com/f/35s8s2-team-gabe

In this issue: Why is advocacy and research on cancer prevention so critical in the fight against cancer in the SDS 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! Understanding World Cancer Day and National Cancer Prevention Month: A Vital Effort for the Shwachman-Diamond Syndrome Community This past week, on February 4, communities from all over the world came together to raise awareness about cancer prevention, cancer care, and the barriers that prevent equitable access to these life-saving measures on World Cancer Day. In fact, the whole month of February marks National Cancer Prevention Month in the United States, a time dedicated to raising awareness about cancer prevention strategies and advocating for healthier lifestyles. In a world where cancer affects millions of lives each year, this month serves as a reminder of the importance of proactive measures in reducing cancer risk. For communities like ours affected by Shwachman-Diamond Syndrome, where the risk of developing cancer, especially myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML), is significantly elevated, this awareness becomes even more critical. Studies have shown that approximately one in three individuals with SDS will develop MDS or AML by the age of 30, underscoring the urgent need for effective prevention strategies within this community. Below is a video by Osmosis that explains what blood cancer (leukemia) is. Although AML is the biggest concern in SDS, it is important to recognize that other types of blood cancers, and several types of other cancers have been reported in SDS patients. See for example this article from France by Dr. Jean Donadieu., which we will summarize in an upcoming issue. World Cancer Day and National Cancer Prevention Month provide an opportune moment to highlight the significance of early detection, healthy lifestyle choices, and regular screenings in reducing cancer risk, particularly for individuals with SDS. While the genetic predisposition to leukemia in SDS cannot be altered (yet!), lifestyle factors such as maintaining a balanced diet, exercising regularly, smoking cessation, and avoiding exposure to environmental toxins can play a crucial role in mitigating overall cancer risk. Moreover, regular medical surveillance and screenings tailored to the specific needs of SDS patients are paramount. Routine blood tests, bone marrow evaluations, and genetic counseling can aid in the early detection of any abnormalities or pre-cancerous conditions, allowing for timely intervention and treatment. Although advancements in medical research have led to the development of targeted therapies and treatment protocols tailored to the unique challenges presented by many cancers, research is still ongoing about how we can better treat MDS, AML, and other cancers in individuals with SDS. As we observe World Cancer Day and National Cancer Prevention Month, let us reaffirm our commitment to promoting health, advocating for access to comprehensive healthcare services, and supporting ongoing research efforts aimed at better understanding and addressing the complexities of cancer risk within the SDS community. By fostering a culture of prevention, education, empowerment, and active participation in all facets of research and therapy development, we can move towards a future where the burden of cancer is significantly reduced, and individuals with rare disorders like SDS can live longer, healthier lives free from the fear of cancer. __________________________________________________________________________________ Why is research on cancer prevention so critical to progress against cancer? This resource from the National Cancer Institute provides an overview of opportunities and challenges in cancer prevention research: http://bit.ly/31oGH8O __________________________________________________________________________________ The Centers for Disease Control and Prevention is working to prevent cancer through a number of innovative programs. Here’s how they are achieving progress against the disease: http://bit.ly/2SlvVvR __________________________________________________________________________________ For more information about World Cancer Day and National Cancer Prevention Month, you can visit these websites: World Cancer Day (Materials available in multiple languages!) American Association for Cancer Research: National Cancer Prevention Month Cancer Prevention Quiz __________________________________________________________________________________ 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: Unveiling the Mysteries: CZI Blog Breaks Down Your Body's Building Blocks – Surprising Answers to Your FAQs Welcome to our timely updates on all things SDS, Science, and Advocacy. We bring you a digest of recent scientific publications, conferences, and other newsworthy content - all relevant to SDS - with links to more details and learning opportunities. Are you interested in anything specific? Did we miss something? Let us know. Email genetics@SDSAlliance.org or message us on Facebook! This is all for you! The Science Snapshot this week contains content modified from a blog post published by the Chan Zuckerburg Initiative (CZI) and written by Samantha Yammine. __________________________________________________________________________________ Revealing the Mysteries of Human Cells In a previous Science Snapshot on Understanding the Role of Genes, we briefly reviewed what cells are, the role of genes as instructions for these cells, and the difference between germline/hereditary variants (i.e., mutations) and somatic/acquired variants. Our bodies are composed of trillions of cells that have many different roles – to help us grow, digest food, protect us against infections, and more. These different tasks are controlled by a set of instructions known as genes. (We even have genes whose purpose is to protect us against cancer!) Genes are made up of DNA, which you inherit from your parents, and they determine things like your eye color, height, and even your risk for certain health conditions. In this week’s Science Snapshot, we will be highlighting an interactive and informative blog post published by the Chan Zuckerburg Initiative (CZI) and written by Samantha Yammine, which answered some of the frequently asked questions about the cells that make up our bodies. How many cells are there in the human body? The current best estimate is that the average body contains about 37.2 trillion human cells. There are more cells making up the human body than the number of seconds in one million years. And about 372 times as many cells making just one body than there are stars in our home galaxy, the Milky Way. And that’s without factoring in the trillions of single-celled microbes living throughout the human body in symbiosis (i.e., these microbes positively benefit the function of the human body just as our bodies support their survival). These trillions of cells are the basic functional unit of our biology, coming together to form the different organ systems in our body. Cells come in many forms and functions — from elongated cardiomyocytes that help the heart contract, to the tree-shaped neurons that transmit electrochemical messages throughout the brain, and biconcave, disc-shaped cells carrying iron throughout our blood. Researchers are working to map all of these different cells in our body to better understand health and disease. Image credit: 10 Questions Revealing the Mysteries of Human Cells How big is a cell? Human cells come in a range of sizes, though most are too small to be seen with the naked eye. The main exception to that is the ovum, or egg cell, which is among the largest cells in the body at about 0.1 millimeters (or 100 micrometers) across. Rival to the unusually large size of the ovum are motor neurons emanating from the spinal cord down to the biggest toe. These are about 100 times thinner in diameter than the ovum, but have a single projection running the length of the leg, reaching up to one meter long. Most other human cells average about 10-100 micrometers in diameter. To picture that scale, imagine a single grain of salt cut into five pieces. Each of those pieces would be about the size of the average human cell — no longer visible without magnification, and so small that about 635 of these cells could fit across the diameter of a penny. The size and shape of a cell is closely tied to its function, and can change over time. The growth and division of cells are very carefully regulated to maintain a healthy state. Does every single cell in my body have the same DNA? For the most part, yes, every cell in the body has roughly the same set of DNA. That’s because all cells in the body originate from the fertilized egg, created through many, many rounds of cell division. Each time the cell divides, it makes a copy of its genetic material so there is enough to be passed on to the new cell. While there are many “proofreading” steps to reduce errors in the process of duplicating DNA, there are approximately 120,000 copying mistakes across the 6 billion bases in the genetic code every time a cell divides. While most of these changes do not amount to any significant changes in the genetic code, they can accumulate as cells in the body continue to divide over our lifetime. While every cell in a person’s body has nearly the same set of DNA, cells become different depending on the subset of the DNA being used. It’s similar to how an orchestra works: all of the instruments are there, but not all of them are getting played at once, and depending on the timing and combination of instruments you can get completely different music from the same set of instruments. While every cell has the full set of DNA, as a cell develops and specializes it uncoils the parts of DNA it needs to use and coils up the parts that are less relevant to its functions. That’s how a muscle cell ends up different from a skin cell, even though they have the same set of genetic instructions. Researchers want to learn more about how differences in people’s DNA, environments, and lifestyles impact their health to formulate more precise treatments and prevention strategies. CZI has partnered with the US’ four historically Black medical colleges to further support their cutting-edge scientific research in this field to accelerate precision health for all. Image credit: 10 Questions Revealing the Mysteries of Human Cells How many different types of cells are there in the human body? Historically the answer has been that there are about 200 different types of cells in the human body, but new technology in the last decade has uncovered many more than that, totalling a couple thousand. For example, we’ve known for over a century that there are four main types of cells in the brain: message-conducting neurons, star-shaped support cells called astrocytes, cells that insulate neuronal connections called oligodendrocytes, and specialized immune cells that survey and respond to changes in the brain called microglia. From the first glimpses of these cells through the earliest of microscopes it became clear there are many subcategories of each of these cell types. But it’s taken advances of imaging technology and molecular biology to fully begin to realize just how varied cells can be. For example, the Tabula Sapiens is a project by the Chan Zuckerberg Biohub San Francisco and CZI to map cells of the human body using molecular data. They have already characterized over 400 different cell types using molecular data from studying 500,000 cells from 24 different tissues and organs. The data in these comprehensive cell atlases put a spotlight on the subtle differences between cells that are key to maintaining health, and help us better detect the early changes that lead to disease. How does understanding the cell’s response to disease allow us to develop new therapies? Diseases result from a change in our body’s function, right down to the level of our cells. By studying which cells are affected in a disease and what changes are happening to everyday cell processes, researchers will be better poised to treat the root cause of a disease. That’s because understanding more about the biology of a disease can enable researchers to identify new targets for medications, better understand disease progression, make more personalized predictions of how someone may respond to a treatment, and develop preventative measures for disease. For example, rare diseases often involve specific genetic mutations or changes to how genes and proteins are regulated, which point to the role they play in our cells. Through the CZI Patient-Partnered Collaborations for Rare Neurodegenerative Disease and Single-Cell Analysis of Rare Inflammatory Pediatric Disease, researchers and patient organizations are partnering to accelerate our understanding of some of the more than 7,000 rare diseases affecting more than 300 million people worldwide. This work not only advances us towards new treatments for these diseases, but gives us a better understanding of basic cellular processes that are important to treating common diseases, too. Image credit: 10 Questions Revealing the Mysteries of Human Cells What are some unsolved problems in cell biology? Each of the 37.2 trillion cells in the human body is like a whole city of biological activity. Each cell is complex with many parts interacting within an ever-changing environment. There is so much we still don’t know about how individual cells in our bodies change over time and how they interact as systems in our tissues and organs. While new technology is giving researchers a front-row seat to that activity, collaboration and open sharing of data and tools is key to transforming this new information into scientific breakthroughs. CZI is building open source software tools to accelerate science, funding important research and launching institutes to do research that can’t be done in conventional environments. For the next 10 years, our goal (of the CZI and SDS Alliance!) is to understand the biggest biological mystery about the human body — the cell. A foundational understanding of how they work will lead to discoveries that will change medicine in the decades that follow. Image credit: 10 Questions Revealing the Mysteries of Human Cells ____________________________________________________________________________ For more information about what are some of the important cellular components, like ribosomes and mitochondria, you can review this previously published Science Snapshot or watch this YouTube video. __________________________________________________________________________________ 10 Questions Revealing the Mysteries of Human Cells. Chan-Zuckerburg Initiative Blog Post Written by Samantha Yammine July 27, 2023 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: Rare Disease Moonshot: Europe’s Public-Private Coalition to Erase the Rare Disease “White Spots” Welcome to our timely updates on all things SDS, Science, and Advocacy. We bring you a digest of recent scientific publications, conferences, and other newsworthy content - all relevant to SDS - with links to more details and learning opportunities. Are you interested in anything specific? Did we miss something? Let us know. Email genetics@SDSAlliance.org or message us on Facebook! This is all for you! Rare Disease Moonshot: Europe’s Public-Private Coalition to Erase the Rare Disease “White Spots” In their latest issue, the DIA Global Forum publication highlights policy advances for rare disease research at the European level. Read the full article here. "The knowledge and infrastructure required to unlock rare disease “white spots,” diseases where there is currently no science or translational capability, call for a different strategic paradigm. The mission of the Rare Disease Moonshot is rooted in boosting public-private collaborations. Many challenges in modern medicine are too big for one organization to tackle alone. They require true collaboration between a diverse network of companies, policymakers, regulators, academics, civil society groups, and patients. Rare diseases present one such challenge." ~The authors of the article highlight. “The Rare Disease Moonshot taps into the potential of complementary organizations committed to accelerating progress in this overlooked field. It includes the patient voice alongside those of researchers and experts in biobanks and data analytics, translational medicine, clinical trials, regulatory science, and the biopharmaceutical industry.” The Patient Voice YOUR VOICE MATTERS! Make it count! Turn hope into action an join us! The patient voice -- or more specifically, patient-reported data -- is crucial for drug development and regulatory approval by the FDA and EMAE for several reasons. Including patient perspectives and experiences in the evaluation process enhances the overall understanding of a drug's effectiveness and safety. Patient-Centric Focus: Incorporating patient-reported outcomes (PROs) ensures that drug development is centered around patients' experiences and the impact of the condition on their daily lives. This patient-centric focus aligns with the goal of developing treatments that genuinely address patients' needs and improve their quality of life. Measuring Treatment Benefits: Patient-reported data provides direct insight into the benefits of a treatment from the patient's perspective. This information is particularly valuable in assessing the drug's impact on symptoms, functioning, and overall well-being, which may not be fully captured by traditional clinical measures alone. Endpoint Selection: Patient-reported outcomes can help inform the selection of meaningful and relevant endpoints for clinical trials. By including endpoints that matter to patients, researchers can design studies that better reflect the real-world impact of a drug, making the results more applicable to patients' experiences. Clinical Trial Design and Recruitment: Patient-reported data is essential in the design of clinical trials, helping researchers determine the appropriate study population, design patient-friendly protocols, and enhance recruitment strategies. This contributes to the overall success and efficiency of clinical trials. Regulatory Requirements: Regulatory agencies, such as the FDA, increasingly recognize the importance of patient-reported data in evaluating drug safety and efficacy. In many cases, the FDA requires the inclusion of PROs in clinical trial protocols, and positive patient-reported outcomes can support a drug's approval by demonstrating its meaningful impact on patients' lives. Labeling and Communication: Patient-reported data can influence the content of drug labels, ensuring that important information about the drug's benefits and risks is communicated clearly to healthcare providers and patients. This transparency aids in informed decision-making and appropriate use of the medication. Post-Marketing Surveillance: Patient-reported data continues to be valuable after a drug is on the market. Monitoring patient experiences and outcomes post-approval helps identify any previously unrecognized side effects, assess long-term benefits, and guide further recommendations for use. Health Economics and Market Access: Patient-reported outcomes contribute to health economic assessments and market access strategies. Demonstrating the positive impact of a drug on patients' lives can influence reimbursement decisions and market access, making the drug more widely available to those who need it. In summary, patient-reported data is integral to the drug development process, providing a comprehensive understanding of a drug's benefits and risks. Its inclusion enhances the credibility of clinical trials, regulatory submissions, and post-marketing evaluations, ultimately contributing to improved healthcare decision-making and better outcomes for patients. YOUR VOICE MATTERS! Make it count! Turn hope into action an join us! Do you enjoy the SDS & Science Snapshots? You can Sign up by using the button on the top right of this post: