By GREGORY ZELLER //
A new gene therapy can literally rewire the brains of Parkinson’s disease patients – and may rewrite the book on treatment of the nation’s second most-common neurodegenerative disease.
A team of scientists from the Manhasset-based Feinstein Institute for Medical Research has published findings indicating that AAV2-GAD, an emerging Parkinson’s gene therapy, creates new circuits in the brain promoting improved motor skills – setting up AAV2-GAD for a critical final found of clinical trials.
Most Parkinson’s disease therapies and medications address symptoms such as tremors, rigidity and imbalance, but do not slow or even address the underlying neural degeneration.
Gene therapy, which injects genes into cells to correct brain-function abnormalities, is gaining steam as a neurogenerative-disorder treatment option – and the Feinstein Institute team discovered that AAV2-GAD’s “mechanism of action” differs from all other Parkinson’s treatments.
Led by Feinstein Institute Professor David Eidelberg, the team examined the mechanisms of the gene glutamic acid decarboxylase, delivered directly into the subthalamic nucleuses of Phase 2 clinical trial patients.
Eidelberg, head of the Feinstein Institute’s Center for Neurosciences, said he and his fellow researchers were surprised by what they found.
“Current Parkinson’s disease therapies act on the abnormal disease network in the brain and often stop working over time as the body builds a tolerance,” noted Eidelberg, also a professor of molecular medicine and neurology at the Donald and Barbara Zucker School of Medicine at Hofstra/Northwell. “What we observed with AAV2-GAD therapy is quite the opposite.”
What they found, according to the paper published Wednesday in the journal Science Translational Medicine, was that AAV2-GAD promotes the formation of new neural pathways in the brain, connecting the subthalamic nucleus to other motor regions and “thereby improving motor symptoms for as long as 12 months,” Eidelberg added.
The study analyzed metabolic PET scans from 15 Parkinson’s disease patients who received the gene therapy and 20 who were randomized to sham surgery – a fake surgical intervention deemed an important scientific control – and then rescanned six and 12 months later.
Patients who received the gene therapy started to form new brain connections. And unlike other Parkinson’s disease treatments soon overcome by the abnormal disease network, these stuck: The new neural pathways matured by the end of the 12-month study.
Eidelberg’s team is now planning a Phase 3 clinical trial, with its sights set squarely on a new and uniquely effective Parkinson’s disease intervention. While the road is long, the Feinstein Institute researchers have already “opened important new avenues for mapping brain networks that are fundamental to understanding debilitating movement disorders,” according to Feinstein Institute President and CEO Kevin Tracey.
“This latest work mapping the therapeutic benefit of AAV2-GAD gene therapy is a major next step to further refining therapies that combat the root causes of the condition,” Tracey said Wednesday.