Targeted epigenome editing as ‘next generation drugs’ for Parkinson’s disease

Share

By 2020, the Parkinson’s Foundation estimates that nearly one million people will be living with Parkinson’s disease (PD) in the U.S. That’s more than the number of people diagnosed with multiple sclerosis, muscular dystrophy and Lou Gehrig’s disease combined. Researchers at Duke are taking action.

Ornit Chiba-Falek, GCB member and associate professor of neurology, collaborated with Boris Kantor, assistant research professor in neurobiology, to pioneer the development of a new therapeutic strategy for PD that targets the machinery that controls the expression of the SNCA gene. Their findings were published online on August 28 in the journal of Molecular Therapy Cell Press.

Overexpression of the SNCA gene, while not the only way people can contract the disease, has been shown to cause PD and related disorders. If researchers can come up with a method to accurately and efficiently manipulate SNCA levels, they can create a gene therapy as a means of precision medicine for patients with PD in whom the disease is caused by SNCA dysregulation.

Chiba-Falek and team created an innovative platform that allows the regulation of gene expression programs to be fine-tuned. “This approach,” Chiba-Falek said, “would be highly attractive for developing ‘smart drugs’ as disease modifying interventions for PD, Alzheimer’s disease and other neurological diseases and pathologies associated with dysregulation of gene expression.”

Their project provided a proof-of-concept for moving forward with a targeted epigenome-editing approach to in vivo validation. Currently, the team is working to validate this system in an animal model using an intergrase-deficient viral delivery method for safer in vivo delivery. “These studies,” Kantor said, “will further establish, validate and determine the safety of the viral vector tool as a novel epigenome-based therapeutic approach for PD.” Chiba-Falek noted that this work will provide the foundation for implementation and further evaluation in clinical trials.


Share