Research

Parkinson’s is the Disease. He Could Be the Cure.

UGA Researcher Anumantha Kanthasamy, Ph.D., Receives Millions in Federal Grants.

For centuries, scientists have tried to crack the mystery of a devastating ailment once called “the shaking palsy.” But Parkinson’s disease, which causes tremors, muscle stiffness and difficulty walking, remains the second most common neurodegenerative disorder in the United States after Alzheimer’s. About 1 million Americans have Parkinson’s, and more than 50,000 new cases are diagnosed annually.

University of Georgia Professor Anumantha Kanthasamy has a plan to fight back. Armed with with nearly $50M in federal funding, Kanthasamy and his researchers at the Isakson Center for Neurological Disease Research have the resources to take on the disease.

We need to detect Parkinson’s disease much sooner, which means we need to identify its diagnostic markers.
Anumantha Kanthasamy, who’s appointed in the College of Veterinary Medicine

researchers have increasingly found evidence that neurodegenerative disorders can be triggered or accelerated by a sick gut.

In 2021, Kanthasamy was appointed as UGA’s inaugural John H. “Johnny” Isakson Chair and Georgia Research Alliance Eminent Scholar in Parkinson’s Research. He is leading a new UGA initiative in brain science, including the state-of-the-art Isakson Center, and he spearheads an effort to recruit interdisciplinary researchers in neuroscience, epigenetics, bioinformatics and translational medicine.

“We need to detect Parkinson’s disease much sooner, which means we need to identify its diagnostic markers,” said Kanthasamy, who’s appointed in the UGA College of Veterinary Medicine. “We also need new therapeutics to stop Parkinson’s from progressing. To do that, we must understand more about the disease’s underlying mechanisms.”

The immediate driver of Parkinson’s is dying nerve cells in a part of the brain known as substantia nigra (black substance), where neuromelanin-rich neurons produce the neurotransmitter dopamine that helps control movement. If these cells die, the brain’s dopamine supply falls, and eventually Parkinson’s symptoms become apparent.

Over the past decade, researchers have increasingly found evidence that neurodegenerative disorders can be triggered or accelerated by a sick gut. A healthy gut helps modulate immune responses. When it becomes chronically unbalanced—or “dysbiotic”—it can drive harmful inflammation that affects the brain.

We look at it more as a disease that can be initiated or spread from the brain to the body’s ‘periphery,’ but also as a disease that could be started from the periphery and then spread to the brain.
Jae-Kyung (Jamise) Lee, Ph.D.,associate professor in the Department of Physiology and Pharmacology.

“There has been an explosion of research and information about what goes wrong in the gut microbiome and how it impacts the brain,” Kanthasamy said. “But our work is different.”

He is leading a research team to understand a gut-microbe-brain communications channel, though with a new therapeutic twist. The gut microbiome includes trillions of bacteria, fungi and viruses, some of which are sending messages to the brain. The UGA team has gene-edited a probiotic to prompt the manufacture of a therapeutic by the patient’s body itself.

Someday, patients could swallow a probiotic pill that metabolizes in the gut to manufacture a small molecule, which circulates through the bloodstream into the brain. There, it would convert to a crucial neurotransmitter for 12 to 24 hours, relieving Parkinson’s symptoms. In animal models, repeated dosing of the gene-edited probiotic provides continuous production of dopamine longer and can reduce or even eliminate side effects from current therapy.

Kanthasamy and his team are also trying to determine if a patient could have Parkinson’s before symptoms begin and too much damage has already occurred. This includes locating “misfolded” alpha-synuclein proteins, which have been found far from the brain, in peripheral nerve terminals in the skin, for example.

“We could someday take a piece of skin tissue, even before the patient develops symptoms, and tell whether this person is likely to develop Parkinson’s,” Anumantha said. “Based on this work, the Michael J. Fox Foundation and NIH are providing grant support to our center’s biomarker discovery program. We hope to develop this potential diagnostic test over the next few years to get one approved for inpatient offices.”