My PD Story

Fingerprinting a Brain Protein for Better Diagnosis and Treatment

While every person with Parkinson’s disease (PD) experiences unique symptoms and progression, all people with PD have a protein in their brain called alpha-synuclein that is not working like it should. Recent studies have shown that each person with PD may have a unique misfolded version of this protein, which may be related to disease severity.

Currently, there are no diagnostic tests available to differentiate PD stages or to help personalize treatment, but Kundlik Gadhave, PhD, recipient of a Parkinson’s Foundation Postdoctoral Fellowship for Basic Scientists, is hoping to change that with his upcoming research.

From his lab at Johns Hopkins University in Baltimore, MD, Dr. Gadhave’s research is dedicated to developing an alpha-synuclein “fingerprinting” method that will work to identify different variants, or strains, of misfolded alpha-synuclein.

With the help of his mentor Xiaobo Mao, PhD, Dr. Gadhave has already developed a key component of this fingerprinting process called a 3D small molecule microarray (3D-SMM). The 3D-SMM consists of a small glass chip that can attach more than 8,000 different compounds, each with unique biochemical patterns for binding to other proteins.

Dr. Gadhave will use these 3D-SMM chips to fingerprint the alpha-synuclein proteins from spinal fluid samples of people with varying stages of PD. Different alpha-synuclein strains should bind to different compounds on the chip, allowing him to distinguish them biologically.

If his hypothesis is correct, alpha-synuclein collected from people with PD-associated dementia will bind to specific compounds. At the same time, alpha-synuclein collected from people with PD with no dementia will bind to different compounds. These experiments will provide valuable insight into the strength of such a diagnostic tool in tracking different types or stages of the PD.

The identified 3D-SMM compounds that bind to misfolded alpha-synuclein may also be able to inhibit the formation of Lewy bodies, which are strongly linked to PD and dementia. The second half of Dr. Gadhave’s research will test whether the compounds found to bind specific alpha-synuclein strains can slow PD from advancing. This research could lead to the generation of personalized PD therapies that use inhibitors capable of counteracting a unique alpha-synuclein strain.

What are Lewy bodies? Lewy bodies are toxic aggregations, or clumps, of alpha synuclein that affect chemicals in the brain, leading to problems with thinking, movement, behavior and mood.

Dr. Gadhave believes this research can improve how we diagnose and treat Parkinson’s. “The lack of diagnostic biomarkers leads to significant diagnostic delays, limits ability to reliably predict the patient’s disease course, and adversely impacts clinical trial development and execution,” he said. “ Completing this research will lead to the development of a new way to define the known and unknown alpha-synuclein strains, which will benefit the biomarker development and build an essential fingerprinting test.”

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