Neuroscientist Awarded $2.9M NIH Grant to Study and Possibly Prevent Side Effects of Levodopa

The National Institutes of Health has awarded a $2.9 million grant to a Feinstein Institutes for Medical Research scientist working to better understand and prevent dyskinesia, a common side effect of the levodopa used to manage motor symptoms of Parkinson’s disease.

The five-year award went to David Eidelberg, a neurologist and neuroscientist noted for his pioneering work into brain networks in states of disease.

Levodopa is widely given to Parkinson’s patients to help with stiffness and slowness of movement. Naturally found in the body, it’s the precursor of dopamine, a signaling molecule that is involved in nerve cell communication.

Often combined with other medications to reduce side effects like nausea, levodopa is carried on circulating blood to the brain. There it’s converted into dopamine, which activates dopamine receptors to improve the workings of movement control centers in the brain.

However, after about five years of daily use, most patients develop levodopa-induced dyskinesias (LID) — uncontrolled, involuntary movements that interfere with daily activities — shortly after each dose. This side effect can be disabling and problematic for long-term Parkinson’s management.

“Since levodopa is regularly used to help ease the effects of Parkinson’s disease, it is essential to understand the therapy’s full effects on the cerebral blood vessels as well as neurons,” Eidelberg, head of the Feinstein’s Center for Neurosciences in the Institute of Molecular Medicine, said in a press release. “With this research, we hope to slow down or stop the development of LID in Parkinson’s patients.”

His study is titled “Neurovascular Effects of Dopamine Replacement Therapy in Parkinson’s Disease.”

Eidelberg is internationally known for using functional brain networks as neurological disease biomarkers to aid in Parkinson’s diagnosis, disease progression monitoring, and treatment assessment. He and his team are believed to be the first to observe uncoupling of the neuronal and cerebrovascular responses to dopamine in Parkinson’s patients, a pronounced occurrence in drug-induced dyskinesias. They seek to understand the neurovascular issues that underlie these dyskinesias by charting changes over time.

“Dr. Eidelberg is a leader in Parkinson’s disease research,” said Kevin J. Tracey, MD, president and CEO of the Feinstein Institutes. “This further support of his work by NIH offers a new path to understand this syndrome.”

In related news, a clinical trial may soon test a potential oral treatment for levodopa-induced dyskinesia, IRLAB Therapeutics announced in a company release. It plans to open a Phase 2b/3 study in the first half of next year assessing the safety and effectiveness of its oral candidate, IRL790, in Parkinson’s patients with these dyskinesias.

A four-week Phase 1b safety and tolerability study (NCT03531060) in 15 Parkinson’s patients in Sweden reported good safety (no serious side effects) and early evidence of possible benefits (drops in scores measuring dyskinesia) in people taking IRL790 compared to those given a placebo.