Optimizing Gene Therapy for Rett Syndrome

Kathrin Meyer, PhD

$221,004 AWARDED

Gene therapy is the most advanced curative approach in RSRT’s Roadmap to a Cure. The concept is simple, deliver healthy copies of the MECP2 gene to compensate for the mutated ones. In prior work, Dr. Meyer contributed to the gene therapy approach currently in development at AveXis. This approach demonstrated profound improvement in the mouse models of Rett, much greater than that of any drug in development, suggesting that significant benefit may be achieved in people. Preliminary studies indicate that safety of this gene therapy will be acceptable for human administration.

This funded proposal is designed to leverage the expertise in Dr. Meyer’s lab to advance our ability to translate gene therapy research into therapeutics for individuals with Rett Syndrome. First, one of the biggest challenges is simply to manufacture large enough quantities to support FDA approval and thereafter permit treatment of Rett Syndrome in the clinic. New, larger scale manufacturing processes must be developed to create the necessary quantities to treat patients. FDA requires studies to demonstrate that the quality of the gene therapy treatment from the new process is equivalent to that manufactured by the initial process. Dr. Meyer’s lab will perform assays with gene therapies produced by different manufacturing processes to advance insights and knowledge for validating the gene therapy.

A second challenge facing therapeutic development programs is the ability to predict how efficacy observed in the laboratory will translate into efficacy in humans. In addition to studying treatment effects in mice, Dr. Meyer’s lab will assess efficacy of the different gene therapies in human “brains in a dish” cell cultures generated from individuals with a variety of different MECP2 mutations. These studies will explore efficacy in human cell lines, supplement insights gained through the study of mice and are expected to accelerate development of future therapeutics.

In summary, the goals of the project are to support and accelerate Rett gene therapy development and to explore whether studies in human MECP2 mutated cell lines can help optimize gene therapy for individuals with Rett Syndrome.

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