CHM Clinical Trial

Investigation of Peroxisomal Biogenesis Disorders

Dr. Matthew Benson’s thesis involves investigating the functional effect of a mutation in PEX6, a peroxisomal gene, in a patient with a peroxisomal biogenesis disorder. This inherited disorder triggers a collection of disabilities including severe vision loss, sensorineural hearing loss, neurologic dysfunction, and vertebral anomalies. Dr. Benson will be performing in vitro studies to understand the effect of PEX6 mutations on peroxisome number and function and he will be treating cells with an inhibitor of peroxisome degradation to determine if the disorder can be rescued at the cell level. This study aims to advance the understanding of the mechanism of disease in patients with peroxisomal biogenesis disorders and highlight a potential therapeutic intervention for these patients.

Gene Therapy for the Treatment of Choroideremia

The results from early clinical trials evaluating the safety and efficacy of gene therapies are now available, and have shown mixed results. While severe immune reactions to viral gene therapies are relatively rare, it now appears that many (or all) participants in these clinical trials experienced some degree of inflammation. Most inflammation was mild and resolved quickly; as a result, it has been assumed that a small degree of inflammation is not harmful to the patient and is a necessary side-effect of gene therapy treatment. The efficacy of viral vectors in these trials, however, has fallen short of expectations, bringing the design and administration of “current-generation” viral vectors into question. In this project, the MacDonald lab is characterizing the immune response produced by eye cells in response to several different viral vectors. By characterizing the response of these cells at the molecular level, we hope to strategically design new vectors and/or select appropriate anti-inflammatory drugs to avoid damaging inflammation and improve therapeutic outcomes.