Ronald Crystal, MD: APOE2 Gene Therapy for Alzheimer Disease

“The gene therapy strategy is to put the E2 even within the brain, produce E2, and then convert, essentially, the brain into a heterozygote or better.”

It has been known for quite some time that the apolipoprotein E4 (APOE4) gene’s presence in a person highly increases the risk of them developing Alzheimer disease, as well as the risk of early onset Alzheimer. However, with the recent developments in the genetics field bringing gene therapy to the forefront of many discussions, the strategy has made its way to the dementia realm.

Using a strategy to alter the genes of those with APOE4 with adeno-associated virus AAVrh.10-mediated gene transfer of APOE2 has shown promise in preclinical studies, prompting those such as Ronald Crystal, MD, a professor and the chairman of the Department of Genetic Medicine at Weill Cornell Medicine, to work toward bringing the therapy to humans.

With help from the Alzheimer’s Drug Discovery Foundation (ADDF), Crystal and colleagues are moving forward with a clinical trial of AACrh.10hAPOE2 CNS therapy in APOE4 homozygotes with early-onset Alzheimer disease.

At the ADDF’s 19th Annual Conference in Jersey City, New Jersey, Crystal sat with NeurologyLive to share his experience with the therapy and its potential in the space.