image: Vikaas Sohal Awarded Grant by SynGAP Research Fund dba Cure SYNGAP1
Credit: Vikaas Sohal and SRF dba Cure SYNGAP1
Mill Valley, CA – March 25, 2025 – The SynGAP Research Fund (SRF) dba Cure SYNGAP1 501(c)(3) announced a $130,000 grant to Dr. Vikaas Sohal at The Regents of The University of California, San Francisco. The grant supports research into new therapies for reversing cognitive deficits in SYNGAP1-related disorders (SRD) by enhancing key brain functions.
Dr. Sohal’s research focuses on cognitive flexibility—the ability to adapt behavior in response to environmental changes—a skill often impaired in individuals with SRD. Utilizing mutant mouse models, Dr. Sohal and his team will assess the role of prefrontal gamma oscillations—high-frequency brain waves that are disrupted in individuals with SRD—in improving cognitive flexibility. His previous work has shown that enhancing these oscillations can reverse cognitive deficits in mutant mice. With this grant, Dr. Sohal aims to confirm these findings in SYNGAP1-specific models and explore new therapeutic strategies to improve cognitive function in SRD patients.
Why We Supported This Project
Individuals with SRD often struggle with adapting to new situations due to cognitive challenges. Dr. Sohal’s research is especially promising because it targets brain activity that is crucial for flexible thinking. By improving how these brain patterns work, this project has the potential to discover treatments that could make everyday life easier for people with SRD and their families.
In a promising leap toward targeted treatments for cognitive challenges in neuropsychiatric disorders, Dr. Sohal and his team are exploring the role of gamma oscillations in the brain. As Dr. Sohal explains, “The goal of our research is to identify brain circuits and patterns of brain activity that play important roles in cognition and can be targeted to improve cognitive functioning in neuropsychiatric conditions. We have been particularly interested in rhythmic patterns of brain activity called gamma oscillations. We have shown that gamma oscillations play a critical role when individuals change their behavior in order to adapt to changes in the external world, and have identified specific circuits which help coordinate these oscillations across different parts of the brain.”
The team’s preliminary findings suggest a compelling connection to SYNGAP1-related disorders. Dr. Sohal elaborates, “Our preliminary data suggests that mutant mice which lack one copy of the Syngap1 gene have difficulty changing their behavior when the rules of a task change, and stimulating circuits which boost gamma oscillations may lead to long-lasting improvements in this ability.” With the SynGAP Research Fund’s financial backing, Dr. Sohal and his team aim to confirm these findings in Syngap1 mutant mice. He notes, “The SynGAP Research Fund has played a critical role in helping us identify SYNGAP1-related disorders as potential applications for our research, and now, we hope to leverage their financial support to complete proof-of-concept experiments that will demonstrate how our approach, targeting gamma oscillations, could serve as the basis for new treatments.”
Building on Previous Research
Dr. Sohal’s earlier studies demonstrated that enhancing gamma oscillations in the brain’s prefrontal cortex improved cognitive flexibility in mice lacking proper neuron function. This new project will build on those findings by applying them to SYNGAP1-specific cases.
From the SRF Community: Leadership Perspectives
“The psychiatric issues faced by patients with SYNGAP1-related disorders are significant, often addressed too late, and frequently lead to crises for families. This remains one of the main unmet needs in our community. Having a researcher of Dr. Sohal’s stature examine our disease with a focus on behavior change is a significant win for our patients. I am hopeful that this work will lead to improved treatments for our loved ones,” says Mike Graglia, Founder of SRF.
SRF’s Chief Scientific Officer, Kathryn Helde, says “We are incredibly grateful to have Dr. Sohal working on a preclinical model of SYNGAP1-related disorders. His work examines the intractable symptom of cognitive inflexibility and has addressed a subset of that in an elegant, futuristic way that may lead to treatments – treatments that may increase cognitive flexibility in humans living with SRD. His initial findings are exciting, and we look forward to future results and any therapeutic strategies that may come from his research.”
Family Donations Make Progress Possible
Dr. Vikaas Sohal stated, “The generous support of families makes a direct impact on advancing this research by providing timely support at a critical stage. Specifically, this support makes it possible to advance from having an exciting idea, to doing the preliminary experiments and getting the proof-of-concept data that is needed to obtain federal funding.”
Anthony Navarro, Resource Mobilization Director for SRF, highlighted the impact of family donations, saying, "Every dollar donated by families fuels progress toward understanding and treating SYNGAP1-related disorders. This work isn’t just about science—it’s about hope." He added, "The generosity of our community is a reminder that together, we can accelerate research that improves lives."
About UCSF
The UCSF Department of Psychiatry and Behavioral Sciences and the Langley Porter Psychiatric Institute are among the nation's foremost resources in the fields of child, adolescent, adult, and geriatric mental health. Together they constitute one of the largest departments in the UCSF School of Medicine and the UCSF Weill Institute for Neurosciences, a cross-disciplinary alliance that leverages UCSF’s unrivaled bench-to-bedside excellence in the neurosciences by bringing together world-class researchers and top-ranked physicians to solve some of the most complex challenges in the human brain.
About SYNGAP1-Related Disorders (SRD)
SYNGAP1-related disorders (ICD-10 F78.A1) is a rare genetic disorder caused by variants on the SYNGAP1 gene that reduce SYNGAP1 protein levels. SRF has identified over 1,530 patients to date, and the number grows weekly. This protein acts as a regulator in the synapses (where neurons communicate with each other). When SYNGAP1 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 SYNGAP1 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 SRF’s Seven Scientific Programs
SynGAP Research Fund has seven scientific programs. These programs reflect SRF’s urgency to develop disease modifying treatments. These include the following:
- BTS - Basic and Translational Science
- Purpose - Drug Repurposing
- SMART - SYNGAP1 Missense Analysis, Research & Therapeutics
- SBOM - SYNGAP1 Biomarkers & Endpoints
- Facilitate - Develop and Share Research Tools and Reagents
- SRDC - SYNGAP1-Related Disorders Characterization
- ProMMiS: Prospective Multidisciplinary, Multisite Study for Clinical Excellence - Natural History Study at Multidisciplinary Clinics
This grant falls into the SBOM program. Biomarkers (e.g. in blood, CSF, EEGs, actigraphy) and clinical measures (ORCA, Bayley, etc.) are required to determine treatment efficacy and disease progression, and may improve diagnostics. SRF has funded over $550K in SBOM grants.
About the SynGAP Research Fund
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. There are sister organizations founded by local families in the UK in 2020, Europe (the Netherlands) in 2022, as well as both Australia & Latin America (Colombia) in 2023. Completely family-led, SRF is a leading funder of SYNGAP1 research having committed over $6.2 million in grants as of the end of 2024.
SRF’s grant program awards one or two-year grants to investigators, physician residents, and clinicians interested in studying SYNGAP1. SRF’s mission is to accelerate the availability of safe and effective treatments that meaningfully modify SRD to reduce suffering for patients and their families. Current funding priorities include essential milestones for clinical trial readiness. You can learn more about SRF and their accomplishments by reading their current Impact Report.
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, The World Orphan Drug Congress, and Research America.