Unravel Biosciences and SynGAP Research Fund (SRF) Announce clinical research to accelerate new and repurposed therapies for SYNGAP1-related disorders

(Press-News.org) Mill Valley, CA – September 10, 2024 – The SynGAP Research Fund 501(c)(3) announced a collaboration with Unravel Biosciences, Inc., an AI-enabled therapeutics company, to initiate a clinical study aimed at generating primary clinical data, uncovering novel therapeutic targets, repurposing existing drugs, and stratifying SYNGAP1-Related Disorders (SRD) patients into subgroups based on their predicted response to selected drugs. This collaboration will utilize Unravel’s rareSHIFT™ discovery services and BioNAV™ AI platform to advance the development of targeted therapies for SRD.

As part of this study, Unravel will employ its proprietary nasal swab collection methodology to gather RNA transcriptomes from SRD patients and matched healthy family members. The study is unique in its dual approach: analyzing a large cohort of patients with diverse mutations and symptoms. The datasets will be processed using Unravel’s BioNAV™ AI-driven drug and target prediction platform, simulating the response of over 40,000 molecules. This will help identify drug candidates that are most likely to be effective for patients with various specific genetic mutations and symptom severities. The results of this study will inform SRF’s clinical translation strategy, generating repurposing candidates as well as novel, optimized therapeutic targets.

Why SRF is Pursuing This Project The Syngap Research Fund (SRF) is deeply committed to finding better treatments for children with SYNGAP1-Related Disorders as quickly as possible. This partnership with Unravel Biosciences is a significant step forward in that mission. By using advanced AI and innovative methods, we aim to rapidly identify the most effective therapies that can improve the lives of SRD patients. Our goal is simple: to find better drugs now that can reduce suffering for people affected by SYNGAP1-Related Disorders.

Building on Unravel Biosciences' Success in Rare Disease Research Unravel Biosciences has a strong track record in rapidly identifying and advancing drug candidates for complex diseases, particularly rare neurodevelopmental disorders. Recently, Unravel expanded its collaboration with the CSNK2A1 Foundation to accelerate the identification of drug candidates for Okur-Chung Neurodevelopmental Syndrome, a condition with genetic similarities to SYNGAP1-Related Disorders. This expansion highlights Unravel’s commitment and expertise in applying AI-driven drug discovery to rare genetic conditions. Additionally, Unravel's platform has led to four clinical trials starting in 2024, including RVL002 and RVL027, further demonstrating the efficacy of their approach.

SRF Family Donations Make Progress Possible “Thank you to our donors who made this project possible. We are eager to leverage Unravel to find more options for our families. Parents are fighting epilepsy, autism, sleep, behavior and multiple other challenges. We need better drugs and we need them urgently,” says SRF’s Founder, Mike Graglia.

What the Scientists Are Saying SRF’s CSO, Kathryn Helde, says,“The Unravel approach is a powerful and fast combination of molecular readouts from patients with AI-driven analysis of bioinformatics. While SRF has supported other drug discovery efforts, they have each looked for answers in a different way. I am excited about this particular effort, and we expect to have candidates in as soon as 3 months.”

“We are excited to partner with SRF on this critical, large-scale study of SYNGAP1 patient drug response,” said Richard Novak, Ph.D., Unravel Co-Founder and CEO. “Our personalized target discovery approach combined with a population-level study to understand drug response differences across SYNGAP1 patients will enable rapid drug development for patients needing effective treatments today. Working directly with a patient population will further accelerate and clinically de-risk SRF’s existing preclinical programs to optimize clinical development strategies.” 

“The role of patient families in advancing science and enabling the research community to find treatments for rare diseases such as SYNGAP1 is critical,” said Frederic Vigneault, Co-Founder and CSO of Unravel. “Many recent advances in our basic scientific understanding of disease mechanisms and early-stage drug development have been made possible by direct financial contributions from families and caregivers of patients, and we are truly grateful for that support.”

About Unravel Biosciences Unravel Biosciences is the first rapid prototyping therapeutics company, integrating AI systems biology computation with rapid in vivo screening and clinical validation of discovered targets with unprecedented efficiency. Unravel leverages its proprietary BioNAV™ platform combining target and drug discovery, preclinical screening, and patient stratification to find treatments for complex diseases. Unravel's platform has led to four clinical trials starting in 2024. Unravel's platform developed RVL002, a first-in-class new small molecule targeting mitochondrial metabolism, and RVL027, a molecule targeting a novel mechanism to treat dystonias. The rareSHIFT™ program provides platform access to foundation and biotech partners to accelerate and clinically derisk therapeutics. For more information, visit www.unravel.bio and www.rareshift.org.

About SYNGAP1-Related Disorders (SRD) SYNGAP1-Related Disorders (ICD-10 F78.A1; ICD-11 LD90.Y) is a rare genetic disorder caused by variants on the SYNGAP1 gene that reduce SynGAP protein levels. SRF has identified over 1,454 patients to date, and the number grows weekly. This protein acts as a regulator in the synapses (where neurons communicate with each other). When SynGAP protein levels are too low, we see an increase in excitability in the synapses making it difficult for neurons to communicate effectively. This leads to many neurological issues seen in SynGAP patients.

Symptoms of SYNGAP1 include primarily neurological issues, including autism spectrum disorder, intellectual disability, epilepsy, hypotonia (low muscle tone), gross and fine motor delays, and visual abnormalities such as strabismus (crossed eyes) as well as gastrointestinal challenges and disordered sleep.

About the SynGAP Research Fund (SRF) The mission of the SynGAP Research Fund (SRF) is to improve the quality of life for SYNGAP1 patients through the research and development of treatments, therapies, and support systems.

SRF was founded in the US in 2018 as a 501(c)(3) US public charity, and families created sister organizations for SRF in the UK in 2020, in Europe (Netherlands) in 2022, and in Latin America (Colombia) in 2023. 

Completely family-led, SRF is the largest non-government funder of SynGAP research having committed over $6 million in grants. The founders cover operational costs, ensuring donations fund science & patient-related programs. SRF’s grant program awards one or two-year grants to investigators, physician residents, and clinicians interested in studying SYNGAP1. SRF grants are intended to help researchers explore novel ideas and answer open questions related to the clinical aspects of and therapies for SRD.

For more on SRF, visit curesyngap1.org or follow @cureSYNGAP1 on LinkedIn, YouTube, Instagram, Facebook, TikTok, or X.

SRF is a member of FasterCures, COMBINEDbrain, Global Genes Foundation Alliance, Everylife Foundation Community Congress, Epilepsies Action Network, Personalized Medicine Coalition, Rare Epilepsy Network, Epilepsy Leadership Council, Alliance for Genetic Etiologies in Neurodevelopmental Disorders and Autism (AGENDA), California Action Link for Rare Diseases, American Brain Coalition, Genetic Alliance UK, Rare Disease UK, Syndromes Without a Name (SWAN UK), Jumpstart Program, Patient Worthy, Autism Brain Net, Innovation and Value Initiative, Rare Disease Diversity Coalition, Cambridge Rare Disease Network, Breaking Down Barriers, Rare-X, Mencap, IndoUSRare, and The World Orphan Drug Congress.

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