Development of a Novel Viral Vector Gene Therapy Approach to treat CACNA1A Cerebellar Disorders

Awardee: Samuel Young

Institution: University of Iowa

Grant Amount: $73,731.00

Funding Period: February 1, 2024 - January 31, 2025

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Summary:

Currently, no clinically approved therapeutic strategy that treats the root cause of CACNA1A disorders exists. Due to the recent clinical successes of viral vector-mediated gene therapy, it is an attractive strategy to treat CACNA1A disorders. However, the CACNA1A cDNA sequence is 7.5 kilobases and 8.4 kilobases complete cDNA, which is too large to be used with Adeno-associated Virus (AAV), since AAV has a ~5 kb packaging capacity. Although AAV is the most widely-used gene therapy viral vector in the clinical setting, it is severely limited to treat CACNA1A disorders. Therefore, non-toxic viral vectors with large carrying capacities that are capable of long-term stable transgene expression in Purkinje cells and potentially other cerebellar cell types are needed. Development of a viral vector gene therapy approach to treat all forms of CACNA1A disorders is critical to mitigate the devastating impact on the quality of CACNA1A patient lives. This proposal represents the first steps towards establishing the feasibility of a novel gene therapy approach for CACNA1A cerebellar disorders. While our research is an early discovery stage project, the ability to generate a viable gene therapy approach will lead to a breakthrough in treating the root cause of all CACNA1A disorders.

Mouse Model for CACNA1A gene mutations and related neurodevelopmental disorders

Awardee: Lisa Manaster

Foundation: CACNA1A Foundation

Funding Period: May 13, 2022