image: Dr. Clement Chow receives Grant from SynGAP Research Fund
Credit: Dr. Clement Chow and SynGap Research Fund
Mill Valley, CA – October 29, 2024 – The SynGAP Research Fund 501(c)(3) has awarded a pair of grants to Dr. Clement Chow, a geneticist and Associate Professor in the Department of Human Genetics at the University of Utah. These grants are crucial steps in advancing therapeutic development for SYNGAP1-Related Disorders (SRD).
Dr. Chow has a strong track record with drug discovery with publications and patients being treated in NGLY1 deficiency, Charcot-Marie-Tooth Disease (CMT4J), Retinitis Pigmentosa, and Congenital Disorders of Glycosylation (NGLY1, PIGA-CDG, DPAGT1-CDG) diseases.
The first grant, awarded in 2023, used a commercially available raskol RNAi knockdown Drosophila (fruit fly) model that replicates the SYNGAP1 mutation observed in patients, providing a critical tool for drug screening. Through this model, Dr. Chow’s team screened approximately 1,600 primarily FDA-approved drugs, leading to the identification of N-acetyl-L-leucine (NALL) as a promising candidate for treating SRD. NALL, a modified amino acid, has demonstrated potential in stabilizing brain function and enhancing cellular processes like autophagy. It has been explored in clinical trials for conditions such as cerebellar ataxia and Niemann-Pick disease type C, where it has shown some efficacy in improving motor function and overall quality of life in patients.
Building on these promising results, the follow-up grant, funded in 2024, supports advanced studies to validate NALL’s therapeutic potential and understand how it may alleviate the symptoms of SYNGAP1-Related Disorders. These preclinical studies are not only critical for fast-tracking potential treatments into clinical settings but also for deepening our understanding of the underlying biology of SYNGAP1 mutations.
NALL was approved by the FDA for NPC on September 24, 2024 under the brand name AQNEURSA™ (levacetylleucine).
Why SRF is Supporting This Project
The Syngap Research Fund (SRF) is committed to advancing the development of treatments that can improve the quality of life for individuals affected by SRD. Drug repurposing is a key strategy in this mission, as it allows researchers to identify potential treatments from molecules that are already known to be safe in humans. By screening existing FDA-approved drugs, researchers can bypass early stages of drug development, such as safety testing, since these drugs have already been approved for other uses. This approach can significantly shorten the timeline from discovery to clinical application, which is critical for families and patients dealing with the urgent and debilitating symptoms of SYNGAP1-Related Disorders.
SynGAP Research Fund’s Scientific Director, Lindsay Wieczorek, PhD, says, “For families grappling with the challenges of SYNGAP1-Related Disorders, the standard timeline of drug and treatment development is simply too long. Each day without an effective therapy feels like an eternity when you’re watching your child and family struggle. That’s why drug repurposing is so critical—It allows us to streamline the process and focus on what truly matters: finding and delivering solutions that can make a real difference now. At SRF, we’re committed to pursuing every possible avenue to bring these treatments to our community as quickly as possible.”
Mike Graglia, Founder of SRF, says “Dr. Chow is exceptionally collaborative. We are lucky to be working with him. This was the fastest follow-on grant we have ever approved, both because of the impact of this work and because Dr. Chow and his lab are such good partners. I encourage all patient advocacy groups to reach out to him.”
Potential Impact of the Research
Dr. Chow’s research has the potential to significantly accelerate the development of effective therapies for SYNGAP1-Related Disorders through the innovative use of drug repurposing. By leveraging existing FDA-approved drugs, this approach can bypass the lengthy and expensive early stages of drug development, focusing instead on identifying compounds that may offer immediate therapeutic benefits for SYNGAP1 patients.
The identification of NALL as a top candidate for treatment demonstrates the promise of this strategy. If further studies validate NALL’s effectiveness, it could be transitioned into clinical trials more quickly than a new drug might be. While this research primarily focuses on SRD, the success of this approach could also provide valuable insights for applying drug repurposing to other rare neurodevelopmental conditions, potentially broadening the impact of these findings.
Dr. Chow highlights the importance and potential impact of this research, he says “we want to help people living with SYNGAP1 however we can. By combining the unique advantages of the fruit fly with drug repurposing we can quickly uncover a potential therapy that may change lives. Drug repurposing holds the potential to help SYNGAP1-related disorders and many other rare diseases.”
Learn more
Dr. Chow shared about his research at the 2023 SYNGAP1 Conference hosted by SRF, the recording is available on the cureSYNGAP1.org site. Also there are two blogs written by SRF at the time of this release about NAL one updating on an early patient experience and another describing potential mechanisms of action. Dr. Chow will be sharing more at the upcoming 2024 SYNGAP1 Conference hosted by SRF in Los Angeles on December 5th.
About Dr. Chow
Dr. Clement Chow is an associate professor in the Department of HUman Genetics at the University of Utah School of Medicine. The Chow lab is committed to transforming basic science into real therapies. They partner with patients, families, foundations, and physicians to make discoveries that may improve the lives of those living with rare diseases.
About University of Utah Health
University of Utah Health provides leading-edge and compassionate care for a referral area that encompasses Idaho, Wyoming, Montana, and much of Nevada. A hub for health sciences research and education in the region, U of U Health has a $492 million research enterprise and trains the majority of Utah’s physicians and more than 1,670 scientists and 1,460 health care providers at its Colleges of Health, Nursing, and Pharmacy and Schools of Dentistry and Medicine. With more than 20,000 employees, the system includes 12 community clinics and five hospitals. U of U Health is recognized nationally as a transformative health care system and provider of world-class care.
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 SYNGAP1-Related Disorders 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) 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.