Genetic models to progress treatments for IQSEC2 related pharmacoresistant epilepsy.

Awardee: Cheryl Shoubridge

Institution: University of Adelaide

Grant Amount: $30,000

Funding Period: March 1, 2024 - February 28, 2025

Summary: This project aims to generate patient derived iPS cells modelling the loss of IQSEC2 to comprehensively evaluate anti-epileptic drugs in reducing seizure activity in a human relevant setting.

Establishment of a female model of IQSEC2-associated disorders and AAV-mediatedtreatment of the phenotypes.

Awardee: Takuma Mori

Institution: Shinshu University School of Medicine

Grant Amount: $15,000

Funding Period: March 1, 2024 - February 28, 2025

Summary: This proposal aims to establish a standard strategy to understand female-specific phenotypes of IQSEC2-associated disorder using rodent models. The objectives of this project are to first produce a humanized mouse with IQSEC2-associated disorders and to investigate the physiological properties of a single neuron. The other aim of this proposal is to examine the possibility of the AAV-mediated treatment of IQSEC2-associated disorder.

A Novel Approach for the Treatment of IQSEC2-mediated Disease.

Awardee: Sahar Isa Da’a

Institution: Sidra Medicine, Qatar Cardiovascular Research Center

Grant Amount: $20,000

Funding Period: March 1, 2024 - February 28, 2025

Summary: Our proposal is centered on implementing a precise and personalized medicine approach to evaluate AMPA receptor modulators tailored for therapy specific to IQSEC2 genetic variants. Employing the zebrafish model, we aim to decipher the molecular and cellular mechanisms influenced by IQSEC2 genetic variants and their impact on neurodevelopment and phenocopying the clinical presentations of patients. The established zebrafish models will serve as a valuable tool for testing potential therapeutic drugs, specifically AMPA receptor modulators, designed for the treatment of IQSEC2-related disorders. The range of AMPA modulators includes Perampanel, known for inhibiting recycling; Ritalin and Aniracetam, recognized for increasing recycling; and PAM (PF-4778574), designed to boost AMPAR activity.