Advancing Research

Meet a Researcher Working to Stop the Spread of Misfolded Proteins in the Brain

Sunil Kumar headshot

Parkinson’s disease (PD) progression occurs in part because of a misfolded protein called alpha-synuclein that spreads in the brain. Alpha-synuclein forms clumps that clog brain cells (including neurons), leading to their eventual deterioration. Over time, the clumping kills neurons and impairs the brain’s ability to produce dopamine, leading to Parkinson’s symptoms.

Sunil Kumar, PhD, a recipient of a Parkinson’s Foundation Stanley Fahn Junior Faculty Award, is working on a new way to stop this spread using foldamers, which mimic the chemical and structural fingerprints of clumping alpha-synuclein and prevent this toxic process.

Foldamers are bioengineered compounds designed to fold into specific shapes, similar to how proteins, like alpha synuclein, fold and behave in the body. Understanding how foldamers fold and their unique structures could lead to the development of new therapeutics.

Dr. Kumar explained that while there is other research being done to prevent alpha-synuclein clumping, his lab’s approach at the University of Denver is unique because they are using foldamer molecules. Many other approaches use either antibodies, which are effective, but large, and have difficulty crossing the blood-brain barrier, or small molecules that are not very specific and therefore not effective in targeting alpha-synuclein.

“We came up with this idea of foldamer molecules, which are as specific as antibodies but they are much smaller in size, allowing them to cross the blood-brain barrier efficiently, which is essential when making a drug for Parkinson’s,” said Dr. Kumar.

“With this foldamer strategy, our lab has identified two or three lead compounds that have advanced through the initial pre-clinical stages,” he said. “We have optimized their activity all the way up to mouse models and they have shown very nice activity to rescue all the Parkinson’s disease phenotypes. We are now in the second phase where we are optimizing their pharmaceutical properties.”

So far, his lab has seen success with this strategy, and he hopes it will lead to a new treatment for people with PD in the future.

“We are very hopeful that once we pass the current testing stage, we can move to the clinical phase and find a drug to stop the progression of the disease or slow it down,” Dr. Kumar said. “This would increase the lifespan of people with Parkinson’s disease, as well as their quality of life.”

Meet more Parkinson’s researchers! Explore our My PD Stories featuring PD researchers.

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