Through its focus on the fuel supply that powers healthy brain function, a transformative study has uncovered both the key cause and an immediate treatment for Parkinson’s disease.
Researchers reported their discovery last week that brain cells in Parkinson’s patients shut down the energy-producing capacity of the mitochondria, resulting in a devastating shortage for cells that normally consume 20 percent of the body’s energy.
The findings indicate that boosting the mitochondria with current FDA approved drugs early on may prevent or delay the onset of Parkinson’s.
Affecting roughly 5 million people worldwide, Parkinson’s disease is a relentless condition that starts killing dopamine neurons in the brain many years before the onset of hallmark symptoms like tremors, muscle rigidity and slow movements. Thus, much-needed drugs to slow or halt the disease would have the greatest benefit for patients if they are given early on, before too many dopamine neurons die.
Clemens Scherzer from Brigham and Women’s Hospital and Harvard Medical School, along with an international team of researchers, now show that a root cause of Parkinson’s disease may lie in 10 gene sets related to energy production that spur neurons in the brain to “divorce” their mitochondria and related energy-producing pathways. The study was published in the journal Science Translational Medicine last week.
Targeting of the master gene regulator, PGC-1alpha, may thus be an effective way to slow down or halt the earliest stages of Parkinson’s, staving off permanent damage and neuronal loss. FDA-approved medications that activate that PGC-1alpha are already available for diseases like diabetes. Instead of having to start from scratch, pharmaceutical companies may be able to dust off their drug libraries and find look-alike drugs capable of targeting PGC-1alpha in the brain.
“The most exciting result from our study for me is the discovery of PGC-1alpha as a new therapeutic target for early intervention in Parkinson’s disease. PGC-1alpha is a master switch that activates hundreds of mitochondrial genes, including many of those needed to maintain and repair the power plants in the mitochondria,” Scherzer said.
Previous studies have linked defects in mitochondrial activity to Parkinson’s disease, but they generally have not provided such a comprehensive, specific set of genes as Scherzer and colleagues now report.
The researchers analyzed brain samples from deceased Parkinson’s patients. At the end of this tour-de-force analysis, 10 gene sets linked to Parkinson’s emerged. All of these gene sets had a common thread—the master regulator gene PGC-1alpha.
Why would the brain, being so highly energy dependent, abandon its entire energy-producing apparatus? That seems to be the core mystery of Parkinson’s disease. Some think that mitochondrial activity may be affected by a combination of genes and the environment.
“I believe that environmental chemicals, risk genes, and aging–each having a small effect when taken separately–in combination may lead to the pervasive electron transport chain deficit we found in common Parkinson’s disease and to which dopamine neurons might be intrinsically more susceptible,” said senior author Clemens Scherzer, Assistant Professor of Neurology at Harvard Medical School.
Glad to see progress. Can hardly wait for the cure!
This is very promising. Both my mother and my husband have PD, and numerous people in my mother’s family had it, including my grandmother and uncle. I really hope that something is available soon to fight this horrible disease.
Amazing. What a great beakthrough. Hope to more about this.