Rutgers scientist helps discover potential new Parkinson's treatment

Scientists at Rutgers University recently partnered with the Scripps Research Institute to discover a small molecule that may help slow down the progression of Parkinson’s disease, according to a press release.

Treatments of Parkinson’s disease currently available only help the symptoms, such as tremor and slow movements, but the brain continues to degenerate, said Dr. M. Maral Mouradian, director of the Rutgers Robert Wood Johnson Medical School Institute for Neurological Therapeutics, who led the research team.

Mouradian said her goal is to find a cure that addresses the underlying problem in Parkinson’s disease: a small protein called alpha-synuclein.

“It has no structure, it keeps changing its shape. When a protein is like that, it is very difficult to target it with a drug,” she said.

The amount of alpha-synuclein present in the brain is an important factor that leads to its build up and clumping in the brains of patients with Parkinson’s disease.

“Think about it like cholesterol,” Mouradian said. “(A) high level of cholesterol is bad for your body because it causes heart attacks and strokes. So, we treat that with statins to try to reduce cholesterol. But cholesterol is still a very important molecule for our metabolism. It’s a similar concept. Alpha-synuclein is an important protein, but if you have elevated levels that can accelerate its tendency to clump and damage brain cells.”

To reduce the amount of alpha-synuclein in the brain, Mouradian and her collaborators went after its messenger ribonucleic acid (mRNA), which she said is easier to target than the shape-shifting protein. She said there is also a part of the mRNA that controls the rate of translation into protein.

“We target it with a compound, a small molecule with drug-like properties, that binds to this regulatory segment and blocks or minimizes translation. By doing so, less protein is produced,” Mouradian said.

To do this,  the team uses a technology developed by Dr. Matthew Disney, a chemistry professor at the Scripps Research Institute.

“When I read about his technology, I said I want to apply this to Parkinson’s disease. So, I reached out to him and we launched a collaboration,” Mouradian said.

The collaboration began approximately five years ago. With funding from a National Institutes of Health grant, the team was able to prove that a drug-like molecule reduces alpha-synuclein production and does not target other mRNAs randomly.

Mouradian said she expects the molecule to get into a Phase I clinical trial in approximately four years, but drug development usually takes at least 10 years and requires more money than it used to.

“It used to be $1 billion, now it takes around $2.6 billion to develop a drug,” she said.

While other products on the market like antisense oligonucleotides (ASOs) also target alpha-synuclein, Mouradian said that the RNA-targeting small molecule method is more selective and convenient for patients.

“The advantage of ours is we’re using a small molecule – they’re using a nucleic acid which is a large molecule, often difficult to deliver. It’s not something you can swallow. Our goal is to develop a pill,” she said.

Mouradian said she is optimistic due to how much the scientific field has learned about Parkinson’s disease in the past 20 years.

“There is hope, and I say this to my patients all the time. There is tremendous research being done in Parkinson’s because we now know so much about the disease pathogenesis and pathology so we can now target the disease in a smart way,” she said. “We know what the problem is at the molecular level and we know how to target it.”

Editor's note: A previous version of this article was titled, "Rutgers scientists discover new Parkinson's treatment." The photo and accompanying photo caption previously related to the Scripps Research Institute.