Drug repurposing offers hope for SYNGAP1 patients

The SynGAP Research Fund 501(c)(3) has awarded two grants to Dr. Clement Chow, a geneticist and associate professor in the Department of Human Genetics at the University of Utah. These grants are critical steps in advancing therapeutic development SYNGAP1-Related Disorders (SRD).

Dr. Chow has a strong track record in drug development with publications and patients treated with NGLY1 deficiency, Charcot-Marie-Tooth disease (CMT4J), retinitis pigmentosa, and congenital glycosylation disorders (NGLY1, PIGA-CDG, DPAGT1-CDG). diseases.

The first grant, awarded in 2023, used a commercially available one Raskol RNAi knockdown Drosophila (Fruit fly) model that replicates this SYNGAP1 The mutation observed in patients represents an important tool for drug screening. Using this model, Dr. NALL, a modified amino acid, has been shown to have the potential to stabilize brain function and improve cellular processes such as autophagy. It has been studied in clinical trials for conditions such as cerebellar ataxia and Niemann-Pick disease type C, where it has shown some effectiveness in improving motor function and overall quality of life in patients.

Building on these promising results, the follow-up grant funded in 2024 will support advanced studies to validate the therapeutic potential of NALL and understand how it may alleviate the symptoms of NALL SYNGAP1-Related disorders. These preclinical studies are critical not only for rapidly translating potential treatments into clinical settings, but also for deepening our understanding of the underlying biology SYNGAP1 Mutations.

NALL was approved by the FDA for NPC on September 24, 2024 under the brand name AQNEURSA™ (levacetylleucine).

Why SRF supports this project

The Syngap Research Fund (SRF) is committed to advancing the development of treatments that can improve the quality of life for people with SRD. Drug reuse is a key strategy in this mission because it allows researchers to identify potential treatments using molecules already known to be safe for humans. By screening existing FDA-approved drugs, researchers can bypass early stages of drug development, such as safety testing, because these drugs are already approved for other uses. This approach can significantly shorten the time from discovery to clinical use, which is critical for families and patients struggling with urgent and debilitating symptoms SYNGAP1-Related disorders.

Scientific Director of the SynGAP Research Fund, Lindsay Wieczorek, PhD, says: “For families grappling with the challenges SYNGAP1-related disorders, the standard time frame for developing drugs and treatments is simply too long. Every day without effective therapy feels like an eternity as you watch your child and family struggle. This is why drug reuse is so important. It allows us to streamline the process and focus on what matters most: finding and delivering solutions that can make a real difference now. At SRF, we are committed to pursuing every avenue possible to bring these treatments to our community as quickly as possible.”

Mike Graglia, founder of SRF, says: “Dr. Chow and his lab are such good partners. I encourage all patient advocacy groups to contact him.

Possible implications of the research

The research of Dr. Chow has the potential to significantly accelerate the development of effective therapies SYNGAP1-Related disorders resulting from the innovative use of drug repurposing. By leveraging existing FDA-approved drugs, this approach can bypass the lengthy and expensive early phases of drug development and instead focus on identifying compounds that may provide immediate therapeutic benefits SYNGAP1 patients.

The identification of NALL as a leading candidate for treatment shows the promise of this strategy. If further studies confirm NALL's effectiveness, it could move into clinical trials more quickly than a new drug. While this research focuses primarily on SRD, the success of this approach could also provide valuable insights for applying drug repurposing to other rare neurodevelopmental disorders and potentially expand the impact of these findings.

We want to help people who live with SYNGAP1 however we can. By combining the fruit fly's unique benefits with drug repurposing, we can quickly discover a potential therapy that can change lives. Reusing medicines can be helpful SYNGAP1-related disorders and many other rare diseases.

Dr. Clement Chow, geneticist and associate professor, Department of Human Genetics, University of Utah