Pitt Researchers Pave Way For Treating The Cause Of Parkinson's, Not Just The Symptoms

Jun 10, 2016

University of Pittsburgh researchers say they made a major discovery that could affect treatment of Parkinson's disease.
Credit Rev. Xanatos / Flickr

Researchers at the University of Pittsburgh said they have made a major discovery that could lead to new treatments for Parkinson’s disease.

Scientists have long known that people whose brains make too much of a protein called alpha-synuclein end up getting Parkinson’s, but they didn’t know why that particular protein was toxic to brain tissue.

“We set out to study whether it was specifically affecting the mitochondria within the cells, which are the power plants that make all the energy we need for all our cellular functions,” said Tim Greenamyre, director of the Pittsburgh Institute for Neurodegenerative Diseases.

Through “luck and a hunch” Greenamyre and his team found that the alpha-synucleins were sticking to a mitochondrial protein called TOM20. TOM20, in turn, is responsible for ushering other proteins from the cytoplasm into the mitochondria. It’s a part of regular maintenance, like one might perform on a car or bicycle.

“(The mitochondria) have to replenish all their constituent components on a regular basis, and when they can’t do this because the synuclein is sticking to them, they sort of become old and inefficient and they produce less energy than is needed and a lot more toxic free radicals which cause damage,” he said.

Greenamyre said this knowledge could open the door to new therapies for Parkinson’s disease. Currently, doctors are only able to treat the motor symptoms of Parkinson’s such as stiffness and tremors, but they are unable to stop the disease from advancing.

One potential treatment option could be gene therapy – modifying cells so that they create extra TOM20 to act as “decoys” for the alpha-synuclein.

“In essence it’s like a sponge to get rid of the toxic alpha-synuclein and then it allows the mitochondria to function normally and produce the energy efficiently like they should,” Greenamyre said.

However, such an approach would likely require brain surgery. Greenamyre said another cheaper and less invasive option might be through the use of peptides, which actually block the interaction between the alpha-synuclein and the mitochondria and “keeps the cells healthy and the mitochondria functioning normally.” He said the peptides could potentially be ingested in a pill form or introduced intravenously.

Researchers are now beginning trials in rodents to see if either approach could stop neurons from degenerating. Greenamyre said it could take one-and-a-half to two years to complete those experiments and publish results. If successful, human trials could begin five years from now.

“Our hope is that this kind of treatment and related kinds of treatments would stop or severely slow the progression of the disease, so that for people who get Parkinson’s disease, if we initiate therapy at diagnosis, we may be able to keep a perfectly normal quality of life for a person’s natural life span,” he said.

The study was published this week in the journal Science Translational Medicine.