Researcher Profile: Using a Virus for Gene Therapy
Apr 22, 2020 12:00 AM
Dr. Collin Anderson, a postdoc in the Pulst lab, received a Junior Investigator Award from the National Ataxia Foundation for his project entitled “Gene therapy in the Shaker rat model of cerebellar degeneration and ataxia.” The work in the grant revolves around the generation of a novel therapeutic strategy to treat a form of degenerative cerebellar ataxia.
Dr. Anderson and colleagues in the Pulst lab have spent several years characterizing the motor, cellular, and molecular abnormalities of the shaker rat, a naturally occurring genetic rodent model of Purkinje cell degeneration, cerebellar tremor, and ataxia. Pulst group member KP Figueroa had previously identified that shaker rats lack a functional NHE6 ion channel, which is necessary for removing hydrogen ions from Purkinje cells and replacing them with sodium ions. In the absence of this channel, Purkinje cells become overly acidic and eventually die, leading to severe ataxia and tremor. Mutations of the gene encoding this ion channel in humans can lead to Christianson Syndrome in humans, which includes a severe, debilitating, progressive ataxia.
Dr. Anderson and colleagues are working to characterize and optimize the effects of a new therapeutic strategy in this model by using an adeno-associated virus that expresses the unmutated gene in Purkinje cells, generating a functional NHE6 protein. Adeno-associated viruses are a particularly attractive method of gene therapy in humans, as they don’t cause disease in humans, don’t replicate, and have long-lasting effects. Additionally, they designed this virus using the newest engineered variant, enabling not only high efficacy with low dose, but ability to cross the blood-brain barrier.
Given the above, success in Dr. Anderson’s work may lead to easier translation than that in most therapeutic strategies. Dr. Anderson and colleagues have already generated strong data showing that this viral therapeutic strategy can delay or even prevent the generation of phenotype. Funded work involves optimizing the therapy and determine a therapeutic window of gene expression. Not only will this work begin the process of developing a translatable therapy for ataxia associated with Christianson Syndrome, but it may prove the concept for using gene therapies to restore missing protein expression in order to treat a degenerative ataxia, which has major implications for the way we treat ataxias.
This is Dr. Anderson’s second time receiving funding from the National Ataxia Foundation, after receiving their 2017 Postdoctoral Research Fellowship in his first year in the Pulst lab. The Pulst group has also received funding for Dr. Anderson’s work from the National Institutes of Health and the Utah Neuroscience Initiative.