Tucson Standard

Researchers at the University of Arizona Health Sciences have identified a protein, PNA5, that may protect brain cells and potentially treat cognitive symptoms associated with Parkinson's disease. This neurological disorder is known for causing tremors and stiffness but also leads to cognitive issues that can progress to dementia. Current treatments address motor symptoms but not cognitive decline.

Dr. Lalitha Madhavan, an associate professor of neurology at the University of Arizona College of Medicine – Tucson, highlighted the prevalence of cognitive impairment in Parkinson's patients: "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."

The research team led by Madhavan and Torsten Falk focused on PNA5, developed by Meredith Hay. Their study published in Experimental Neurology suggests PNA5 has a protective effect on brain cells in animal models. Kelsey Bernard, a postdoctoral researcher and first author of the study, explained their approach: "With PNA5, we're targeting cognitive symptoms but, in particular, we're trying to prevent further degeneration from occurring."

Inflammation is believed to play a significant role in neurodegenerative diseases like Parkinson's. Bernard noted that microglia, immune cells in the brain, can become overactive and cause damage: "In Parkinson's disease when they're constantly activated, microglia can propagate further damage to the surrounding tissue." The researchers observed that treatment with PNA5 reduced levels of an inflammatory chemical linked to cognitive decline.

PNA5 was developed by Hay with Robin Polt from U of A College of Science by modifying a naturally occurring chemical to enhance its ability to enter and remain in the brain longer. Hay is also exploring its potential for treating other dementias such as vascular dementia and Alzheimer's disease.

Madhavan expressed optimism about developing a drug based on PNA5 for alleviating cognitive symptoms in Parkinson’s patients while acknowledging they might still need medication for motor symptoms: "I think about it as a cog in the wheel — there are going to be other drugs that support other aspects of Parkinson's."

Future research will focus on identifying biomarkers and refining dosages among other objectives. Madhavan concluded: "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."

This work was supported by grants from organizations including the Michael J. Fox Foundation and National Institutes of Health.