Dup15q Alliance

We would like to thank Ultragenyx for being a sponsor of the 2024 Research Symposium. The Angelman Syndrome Foundation + Dup15q Research Symposium fosters a space where diverse opinions and a wide range of expertise can unite. The Research Symposium brings together an outstanding community of researchers and clinicians to share unpublished work, participate in conceptual discussions and reflect on the big picture as it relates to Angelman Syndrome, Dup15q Syndrome, and pathways toward effective treatments. It provides the opportunity to educate and inspire our future scientists. In 2024, we are proud to offer collaborative training with Angelman Syndrome Foundation, to provide even more opportunities for professionals to receive training and resources based on the 15th chromosome abnormalities. #Ultragenyx #Dup15q #ASF #Research

The community, now known as the Dup15q Alliance, was initially established in 1994 as the IsoDicentric 15 Exchange, Advocacy and Support (IDEAS), a network offering information and support to families with individuals diagnosed with IsoDicentric 15 or other Chromosome 15 abnormalities. A decade later, in 2004, with 250 members, the organization officially became a nonprofit with 2 major focus areas 1. Providing resources, education, and assistance to families affected by IsoDicentric 15 and related disorders. 2. Uniting families, researchers, and professionals; and promoting research, awareness and understanding of IsoDicentric15 and related disorders. Transitioning to a nonprofit status was a significant effort, requiring extensive work. Special recognition goes to Todd Luchsinger, Evelyn O’Dell, Brian Gazewood, and Nicole Cleary for their contributions. Today, we have over 2,200 families worldwide affiliated with Dup15q Alliance.

LEARN Dup15q Genetic Report Curation In October 2023, the genetics clinician review team, Ana Forsythe and Katie Garbarini, set out to review and validate diagnoses on the 173 Dup15q genetics reports in the LADDER database. From the dataset, they confirmed a Dup15q diagnosis for 96% of uploaded reports. Next, the team curated the information to build a comprehensive dataset with details describing frequency in copy number variation, structure, duplication size, and parent of origin. Interestingly, in addition to traditional interstitial duplication (3 copies of the 15q11.2-13.1 region) and isodicentric duplication (4 copies), three individuals within the dataset were found to have up to 6 copies of 15q11.2-13.1. This copy number variation was caused by either a supernumerary isodicentric or ring chromosome. Another noteworthy finding relates to mosaic Dup15q cases. Typically, individuals with Dup15q have extra copies of the 15q11.2q13.1 region in all their cells; however, individuals can be “mosaic” for Dup15q, meaning that only some of their cells have the genetic change causing Dup15q. In the validated dataset, 12 participants were confirmed as having mosaic Dup15q syndrome. Why is this important? This is the first large-scale genetic subtype validation effort on a diverse Dup15q dataset. This achievement is foundational to using LADDER because it provides concrete and validated genetic subtype data for researchers and industry partners interested in Dup15q drug development. In fact, these data are currently being prepared for a forthcoming publication on seizure management in Dup15q, with an expected publication by the end of this year.

The DREAM (Dup15q Research Engagement, Activities, and Mechanisms) Fund grant program opportunities: https://lnkd.in/ecWdxFYM This is intended to fund small proof-of-concept studies with a translational focus to generate data for future large-scale research initiatives and funding. Applicants may request up to $50,000 in direct costs to be expended within 12 months. Applications are open to research investigators affiliated with an academic institution, hospital system, non-profit institution, or other accredited research institutions based in the United States (U.S.) or internationally. We are looking to support proposals related to the following areas: Biomarkers and clinical endpoints development; Molecular pathobiology and genotype-phenotype relationships; The role of hypotonia in disease progression and outcomes; Drug repurposing; and Pubescence and disease trajectory. All proposals will undergo rigorous peer review by the Dup15q Alliance and experts within our research and clinical networks. Interested applicants should see the full instruction package and may contact research@dup15q.org and carrie.howell@dup15q.org with any questions about the application process. Proposals will be accepted on a rolling basis until August 1, 2024.

Since 2003, the Dup15q Alliance has sponsored research roundtable meetings. These meetings provided an opportunity for researchers to discuss their current research on chromosome 15q duplications, engage in conversation with the Dup15q Alliance Board of Directors regarding future research priorities, and explore opportunities for future collaborations. In 2014 for first time, we partnered with the Angelman Syndrome Foundation to put on a joint scientific meeting. We continued to bring together an outstanding community of researchers and clinicians to share unpublished work, participate in conceptual discussions, and reflect on the big picture as it relates to Dup15q Syndrome, Angelman Syndrome, and pathways toward effective treatments. It provides the opportunity to educate and inspire our future scientists. Why did we join forces? Angelman syndrome is caused by a deletion of the same region of chromosome 15q that is duplicated in Dup15q syndrome. Those with Angelman syndrome have too little; those with Dup15q have too much. Given the close relationship between the syndromes, those who work on one of the syndromes are often interested in the other.

What a great opportunity for caregivers and those interested in understanding the basics of biotech and drug discovery to attend a free course to increase your knowledge. Knowing Dr. Fink for a few years now, I can say, you don't want to miss this opportunity!

Trial to Study: Affects of Bexicaserin on Seizure Reduction Longboard Therapeutics recently initiated a trial to study the effects of Bexicaserin on seizure reduction in patients with developmental and epileptic encephalopathies, including Dup 15q syndrome. Longboard recently announced additional positive data from their Open Label Extension. An Open Label Extension allows all participants of the Phase 2 study to continue taking study drug and those who were taking placebo in the first phase are then given Bexicaserin. We are excited to share this interim analysis of the PACIFIC study's Open Label Extension (OLE) related to bexicaserin's development program. Here are the highlights: • Bexicaserin achieved an overall median seizure reduction of 56.1% in countable motor seizures over an approximate 6-month treatment period; participants randomized to the PACIFIC placebo group achieved a median seizure reduction of 57.3% • Favorable safety and tolerability results observed • 100% of participants who completed the PACIFIC Study entered the OLE In addition, an End of Phase 2 Meeting has been scheduled with the U.S. FDA for this summer, which keeps us on track for initiation the global Phase 3 program later this year. This is an important step towards potentially new, meaningful treatment for DEE patients, including individuals affected by Dup15q syndrome.

Check out the Dup15q Alliance's NEW Science Spotlight Newsletter from Ryan Rogers-Hammond, Ph. D., Dup15q Director of Scientific and Clinical Initiatives. Read online here: https://lnkd.in/e8VFua3q #Dup15q #Research #Believe #ScienceSpotlight #Newsletter #ClinicalInitiatives #LearnTreatCure #Community

We are so sad to see Dr. Ryan Rogers-Hammond leave the Alliance. She has done an incredible amount of work over the last year. We have moved our Science Director role to full-time. If you know of someone who may be interested in joining our team, please share the link below. https://lnkd.in/eZfuban7

Today we are focusing on the TREAT component of our Learn- Treat - Cure initiative for our science and research strategy. To TREAT the disorder, the Dup15 Alliance will promote and support research that informs strategies to improve patient quality of life through symptom management and elimination. Let's break down how Dup 15q clinics play an important role in connecting patients to clinical trials, from our latest Science and Clinical Initiatives (SCI) Spotlight Newsletter. Read online here: https://lnkd.in/eSCAf_3u #Dup15qResearch #Believe #LearnTreatCure #Treat #Dup15qClinics