Dr Nofar Mor

Sheba Hospital

Amount

$25,000

ASO Therapy to Increase STXBP1 Protein

With the laboratory of Dr. Nofar Mor at Sheba Medical Center, we are evaluating an antisense oligonucleotide (ASO) designed to correct a splicing error in the healthy STXBP1 allele. By restoring proper RNA processing of the intact copy of the gene, the ASO increases the production of correctly formed STXBP1 protein in patient-derived neurons. Because this approach targets the functional allele, it has the potential to benefit individuals across a wide range of STXBP1 mutations.

Dr Omer Revah

The Hebrew University

Amount

$80,000

Organoid-Based Platform for STXBP1 Treatments

With the laboratory of Dr. Omer Revah at the Hebrew University of Jerusalem, we are developing advanced STXBP1 organoid models to study neuronal network function and evaluate therapeutic responses. Using human-derived brain organoids alongside electrophysiological recordings both in organoids and in transplanted rat models, this project enables high-resolution characterization of synaptic activity and treatment effects in a physiologically relevant system. This platform provides a powerful experimental bridge between cellular models and in vivo brain circuitry, supporting the development and testing of potential therapies for STXBP1-related disorders.

Prof Dan Kaganovich and Dr Triana Amen

Southampton University

Amount

$100,000

Small-Molecule Screening to Increase STXBP1 Stability and Protein Levels

With Prof. Dan Kaganovich and Dr. Triana Amen at the University of Southampton, we are developing an early-stage screening platform to identify small molecules that increase STXBP1 protein levels, improve its stability, and strengthen its binding to syntaxin-1A. Using a cell-based system expressing fluorescently tagged STXBP1, the team visualizes and quantifies protein abundance, localization, and aggregation in vitro. A focused library of candidate compounds is being evaluated in this system, providing an efficient first-pass filter for discovering promising molecules that can later be advanced into organoid and in vivo testing across STXBP1 mutations.

Dr. Efrat Ben-Zeev

Weizmann Institute of Science

Amount

$25,000

Computational Modeling to Identify STXBP1-Stabilizing Molecules

With Dr. Efrat Ben-Zeev, we are developing a computational modeling platform to predict small molecules that can stabilize STXBP1 and enhance its binding to syntaxin-1A. Using structural modeling and molecular dynamics simulations, the platform identifies candidate compounds predicted to improve STXBP1 folding, stability, or interaction with syntaxin-1A. This computational pipeline guides the design of focused experimental screens and accelerates the discovery of potential therapeutics for STXBP1-related disorders.

Prof Illana Gozes

Tel Aviv University

Amount

$50,000

R292C Mouse Model for STXBP1 Mechanistic and Therapeutic Studies

With the laboratory of Prof. Illana Gozes at Tel Aviv University, we are developing and characterizing a genome-edited STXBP1 R292C mouse model that mimics the human mutation. This project enables the study of molecular, cellular, and behavioral consequences of the variant in a controlled in vivo system. By analyzing protein expression, synaptic integrity, and functional phenotypes, the model provides a foundational platform for testing therapeutic strategies aimed at restoring STXBP1 levels and improving neuronal function.