Study: Cellular Defects in Energy-making Key to Parkinson's

Researchers could be closer to more effectively preventing and treating Parkinson’s disease after a Harvard-led study discovered that defects in cellular energetics may lead to the disease.

The study—which was published Wednesday in the journal Science Translational Medicine—analyzed gene sets in 410 samples from patients with symptomatic Parkinson’s disease. Researchers found 10 gene sets that pinpointed defects in cellular processes that produce energy, including processes in the mitochondria, an energy-making organelle in human cells. The researchers identified a gene that could serve as a “switch” to increase cellular energetics.

“We found that this energy-producing machinery was controlled by a regulator switch, which pointed us toward a mechanism to how we could reverse this reduced activity,” said Clemens R. Scherzer, an assistant professor of neurology at Harvard Medical School and senior author of the study.

This “regulator switch” is a gene named proliferator-activated receptor gamma coactivator-1 alpha (PGC-1 alpha). Reactivating the PGC-1 alpha gene could lead to proper modulation of cellular energetics that would then help patients at risk for or suffering from Parkinson’s disease, Scherzer said.

Patients with Parkinson’s disease lose a specific type of brain cell called dopaminergic neurons, which play a role in controlling voluntary movement. An activated PGC-1 alpha gene blocks the toxic effects of Parkinson’s disease, protecting these neurons.

“I thought that [the study] really convincingly shows that there are mitochondrial defects in Parkinson’s disease that occur very early and are not just located in the cells that degenerate,” said J. Timothy Greenamyre, a University of Pittsburgh neurology professor who directs the Pittsburgh Institute for Neurodegenerative Disease.

“There have been hints of this for probably a good 20 years, but this really pins it down definitively,” he added.

Drugs that can turn on the PGC-1 alpha gene have already been designed for patients with diabetes. Pharmaceutical companies can now test similar medications for patients with Parkinson’s.

The researchers added that further work is still needed.

“We’re still a long way from the cure, but it’s exciting because it restores hope for the patient population,” said Marcia A. McCall, a research coordinator at the University of Southern Florida.