image: Prof. Zempleni and the UNL Logo
Credit: University of Nebraska Lincoln
Mill Valley, CA – July 10, 2024 – The SynGAP Research Fund 501(c)(3) announces a $190,636 grant, for work to be done in 2024 and 2025, to Professor Janos Zempleni, PhD of the University of Nebraska-Lincoln, to establish data required for regulatory approval for his novel treatment using an engineered version of naturally-occurring particles called exosomes. His first grant from SRF established the engineered changes required to accumulate exosomes in the brain. SRF is pleased to support the continued development of a non-invasive and targeted delivery system for therapeutics to treat SYNGAP1-Related Disorders (SRD).
Why We Supported This Project
SynGAP Research Fund’s mission to accelerate the development of treatments for SYNGAP1-Related Disorders includes a broad range of steps that it takes to go from idea to medicine. Every therapeutic strategy requires a delivery system, and Professor Zempleni’s delivery system was optimized in his previous SRF- funded project. The current grant advances the engineered exosome delivery system loaded with SYNGAP1 mRNA to safe and effective use in patients, from its current status: effective in animal studies. To move into humans, regulatory agencies will require answers to questions such as:
- What is the shelf-life of the therapeutic delivery system?
- What is the appropriate dosage and frequency of treatment?
- Will there be an immune, kidney, or liver response to this therapeutic?
- What is the half-life in the body when administered?
Building on Promising Early Results
Professor Zempleni gave SRF a wonderfully accessible presentation back in March of 2022 that explains exosomes to a broad lay audience. Exosomes are naturally occurring vesicles that are being engineered and harnessed for delivery of multiple types of drugs, from precision medicine (DNA, RNA) to proteins and small molecules. His research has identified signals that can be added on the surface that help the exosomes target the brain and escape clean-up by immune cells. In addition, he has shown that multiple types of cargo can be packaged in exosomes, given to mice, and that the cargo can be found in mouse brains.
Professor Zempleni also presented at the SRF SYNGAP1 Science Conference in November 2023. He states, “I am fortunate to be part of this excellent program. I am confident that our efforts will pay off.”
“Professor Zempleni’s research is absolutely cutting edge— harnessing a natural process of how cells communicate and turning it into a delivery system to make more SynGAP. SYNGAP1 science and our loved ones are lucky to have him on the case,” per Hans Schlecht, MD, MMSc, SRD parent and advocate.
“The research conducted by Professor Zempleni is a prime example of the world-class, transformational research conducted in the College of Education and Human Sciences,” said Nick Pace, acting dean of the College of Education and Human Sciences at the University of Nebraska–Lincoln. “With support from the SynGAP Research Fund, Professor Zempleni’s efforts to help SynGAP patients are amplified and will hopefully result in effective treatment and therapies.”
“The work ahead is exciting, as we see multiple treatments in development get closer to being in humans. The development of therapies that improve the functioning of cells and tissues that currently don’t have enough working SynGAP protein – that is the unifying goal for everything SRF does, said Kathryn Helde, Chief Scientific Officer at SRF. She continues: “The idea that exosomes could be used for multiple types of therapeutics gives me additional hope for reducing suffering for our loved ones and our families.”
SRF Family Donations Make Progress Possible
“I am grateful to SRF’s donors – our families and their friends – who have trusted us and enabled us to make impactful grants like this one,” says Mike Graglia, Founder & CEO of SRF. He continues, “Professor Zempleni is a strong partner and understands that our support arrives from families caring for very ill patients; they are eager to see real progress. We are indeed fortunate to have put SYNGAP1 on his radar and brought him into #TeamSRF.”
About the Zempleni Lab
The Zempleni lab has pioneered research on natural nanoparticles (“exosomes”) in milk and their utilization in the delivery of therapeutics to hard-to-reach tissues with heretofore unknown specificity and efficiency. “We will apply our expertise to find treatments and perhaps a cure for SYNGAP1 patients.”
About the College of Education and Human Sciences at the University of Nebraska–Lincoln
The College of Education and Human Sciences at the University of Nebraska–Lincoln is dedicated to enhancing the lives of individuals, families, schools, and communities, and strengthening the relationships among them. The work of the college in the areas of teacher preparation and school leadership, health and wellness, human development, family science, textiles, apparel, and the hospitality industries is aimed at one thing: helping people achieve their maximum potential. Learn more at cehs.unl.edu.
About SYNGAP1-Related Disorder (SRD)
SYNGAP1-Related Disorder (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.