Early Research Points to Possible New Parkinson's Drug

By Ernie Mundell, HealthDay Reporter

THURSDAY, Dec. 19, 2024 -- Parkinson's is a relentless disease for which few treatments, and no real cure, exists.

Now, researchers say they are on the trail of a potential new therapy for the disabling neurological illness.

As investigators at the University of Arizona in Tucson explained, this is early research, still in the animal-testing stage. However, their findings, published recently in the journal Experimental Neurology, found that a protein called PNA5 appears to shield the brain cells of mice bred with a Parkinson' s-like disease from the ravages of the illness.

"With PNA5, we're targeting cognitive symptoms but, in particular, we're trying to prevent further degeneration from occurring," lead study researcher Kelsey Bernard, a postdoctoral researcher in neurology at the university, said.

"By going down the protective route, we can hopefully prevent cognitive decline from continuing," she added in a university news release.

According to the U.S. National Institute of Neurological Disorders and Stroke, over 500,000 Americans are diagnosed with Parkinson's disease. However, because early symptoms often go undiagnosed, the actual number of people with the illness could reach 1 million.

Senior study author Dr. Lalitha Madhavan said it is crucial to catch and treat Parkinson's disease early. Symptoms that harm cognition are incredibly challenging to treat.

"When patients are diagnosed with Parkinson's disease, 25% to 30% already have mild cognitive impairment. As the disorder progresses into its later stages, 50% to 70% of patients complain of cognitive problems," said Madhavan, associate professor of neurology at the university. "The sad part is we don't have a clear way to treat cognitive decline or dementia in Parkinson's disease."

The microscopic PNA5 protein used in the study was first developed for research by Meredith Hay, a professor of physiology at the university.

As Bernard explained, the origins of Parkinson's remain mysterious, but brain cells called microglia are thought to be key players.

Inflammation within the brain may push microglia into a "supercharged" state.

"Normally, microglia are looking for things like viruses or injury and secreting substances that block off the damage," Bernard explained. "In Parkinson's disease, when they're constantly activated, microglia can propagate further damage to the surrounding tissue. That's what we see in Parkinson's brains, particularly in regions associated with cognitive decline."

Hyperactive microglia can flood brain tissue with chemicals that further inflame neurons, which are key to thinking and memory processes.

However, treating the Parkinson's-model mice with PNA5 appeared to lower the animals' blood levels of the inflammatory chemical.

The team also found that mice lost fewer and fewer precious brain cells.

Other university researchers have also tweaked the structure of PNA5, allowing it to enter the brain more quickly and stay there longer.

It's still early days, and animal research sometimes doesn't translate to people. However, the researchers believe that PNA5 shows promise.

"PNA5 seems to have a possibility of stopping or delaying Parkinson's progression to some extent and could improve the health of brain cells or prevent cells from dying," Madhavan said.

She believes PNA5 might also curb other brain diseases, such as vascular dementia and Alzheimer's disease.

"It has already been tried and tested in other models, and that makes me more optimistic," she said.

In the end, PNA5 might not curb all Parkinson's symptoms but could be used alongside other meds.

"I think about it as a cog in the wheel -- there are going to be other drugs that support other aspects of Parkinson's," Madhavan said. "Taking multiple drugs is never fun, but it's a complex condition and there can only be complex solutions. The beauty of the brain is the interconnectedness, but it also adds to the complexity."