$230K grant awarded to The Jackson Laboratory (JAX) to advance translational research on SYNGAP1-Related Disorders

(Press-News.org) Mill Valley, CA – December 4, 2024 – The SynGAP Research Fund (SRF) has awarded a $230,000 grant to The Jackson Laboratory Rare Disease Translational Center to characterize a mouse model for SYNGAP1-Related Disorders, (SRD), a severe neurodevelopmental disorder marked by seizures, intellectual disabilities, and motor and behavioral challenges. 

This work, under Matthew Simon Ph.D., senior study director and lead scientist at The Jackson Laboratory (JAX), will focus on the characteristics of the SYNGAP1-Q503X mouse model, which mirrors a specific patient variant of SRD. 

A key SRF partner, Tevard Biosciences, will use the SYNGAP1-Q503X model to test their innovative tRNA suppressor therapy, as illustrated by Tevard’s CEO at the 2023 SYNGAP1 Conference.

Why We Supported This Project While many RNA modulating and gene replacement strategies work on all types of premature stops, a class of treatments called tRNA suppressors correct specific nonsense variants, and they work for many different disorders. To reduce barriers to bringing tRNA suppressor therapies for SRD into trials, and with collaborative engagement with Tevard Biosciences, SRF funded the creation and characterization of the SYNGAP1-Q503X mouse model. 

Researchers can order this model through JAX, ultimately making it possible to test and compare therapeutics from more industry partners working on other precision medicines for SRD. 

Building on Foundational SYNGAP1 Research SRF is committed to providing reagents – animal models and patient samples – for research. SRF’s first grant to Dr. Rick Huganir’s Lab led to the creation of two patient-based mouse models of SYNGAP1-Related disorders (SYNGAP1-C.3583-9G>A and SYNGAP1-L813RfsX22). 

JAX hosts an extensive repository of SYNGAP1 mouse models, including the initial research tools that either knockout the gene or conditionally restore its function; these have been the tools for much of what is known about SYNGAP1 biology in mice. JAX houses both of the patient-derived models of SYNGAP1-Related disorders from Huganir and a fully humanized SYNGAP1 model–which replaces the 35kb mouse locus with the 33kb human locus and includes the human AS1 transcript in the 3’ region–donated by the Prosser Lab at Penn.

Voices from the SRF Community and Partners “As more and more biotechnology companies work on developing therapies for SRD, the need for a CRO with expertise in SYNGAP1 animal models becomes more acute,” says Mike Graglia, founder and CEO of SRF. “Not all companies have animal facilities and many of the existing academic labs are at capacity. Anticipating this bottleneck, SRF is investing in the expertise at JAX, specifically related to our mouse models, so that companies have a strong option for testing their assets. It has been a pleasure to work with the team at JAX and we are looking forward to seeing the results of this investment.”

“At the JAX Rare Disease Translational Center, we are excited to be working with the SynGAP Research Fund to produce a new patient-derived research model for the SYNGAP1 community,” said Matthew Simon, Ph.D., senior study director and lead scientist at JAX. “By working directly with Mike and Kathryn and the families they represent, we are able to bring their perspectives and priorities into alignment with the science and resources we are building to better serve the SYNGAP1 and rare disease communities. Together with dedicated advocates and parents, we can focus our efforts to generate, validate, test and share mouse models as a platform for the basic and translational research communities that will see new therapies developed and delivered to the clinic.”

Gregory Robinson, Ph.D., Chief Scientific Officer at Tevard, commented, “Tevard’s work in epilepsy has greatly benefited through use of the SYNGAP1-Q503X mouse model. With it, our teams at Tevard will confirm that our Suppressor tRNA approach can restore protein function lost due to the nonsense mutation associated with a broad range of genetic epilepsies including with SYNGAP1. We look forward to continuing our collaboration with SRF in investigating this important animal model for this devastating disease, which currently has no effective, disease-modifying therapies.”

Kathryn Helde, Ph.D., SRF’s Chief Scientific Officer, is excited to be working closely with the team at JAX. “Dr. Matthew Simon has the expertise to guide us and the flexibility to collaborate with us. As we get new data from the project, we evaluate and streamline the second half of the characterization to get high quality observations for our research partners. Working with the Rare Disease Translational Center allows us to use our donations in the most effective way possible.”

Family Donations Make Progress Possible Donations from the SYNGAP1 community are crucial for enabling SRF’s mission. The contributions of SRD families directly support research like this, fostering innovation that offers hope to affected individuals and families.

As Dr. Matthew Simon at JAX notes, “The inspirational and insightful contributions of advocates and parents from SRF on behalf of their families not only keep the research moving ever forward, they remind us how powerful a community of dedicated individuals can be.”

“We rely on donations from families and we are committed to ensuring every dollar donated makes a meaningful impact,” said Anthony Navarro, Resource Mobilization Director at SRF. “We are grateful to every family who supports SRF and allows this critical work to continue.”

About JAX’s Rare Disease Translational Center JAX is an independent, nonprofit biomedical research institution with nearly 3,000 employees in locations across the United States, Japan and China. Its mission is to discover precise genomic solutions for disease and empower the global biomedical community in the shared quest to improve human health. The Rare Disease Translational Center serves that mission by empowering rare disease solutions through partnership, innovation, and scaled pre-clinical pipelines to deliver targeted therapies from lab to clinic swiftly and effectively. The center aims to provide patients with an efficient path from diagnosis to therapy, allowing them to live longer, healthier lives. 

About Tevard Biosciences Tevard Biosciences is a pioneer in creating tRNA-based therapies for a broad range of genetic diseases, including in heart disease, neurological disorders, and muscular dystrophies. Tevard’s leading Suppressor tRNA platform has resulted in the first compelling findings showing restored protein levels and improved function across disease categories in in vivo models of genetic “nonsense” mutations. Tevard’s team is efficiently advancing its programs toward clinical trials, including through a collaboration with Vertex Pharmaceuticals to develop novel tRNA-based therapies for patients with Duchenne muscular dystrophy (DMD). Tevard joined the Lilly Gateway Labs community by relocating to Eli Lilly and Company’s newest R&D facility in Boston, MA. For more information, please visit www.tevard.com.

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 1,497 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 SRD include primarily neurological issues including autism spectrum disorder (ASD), intellectual disability, epilepsy, hypotonia (low muscle tone), gross and fine motor delays, global developmental delay, 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) dba Cure SYNGAP1 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 $6.2 million in grants. The founders cover operational costs, ensuring that 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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