US study suggests BMS’ cancer drug could target Parkinson’s-causing protein

The progressive neurodegenerative condition affects more than ten million people worldwide

Researchers from Johns Hopkins Medicine have revealed that a cancer drug could be used to target a Parkinson’s disease (PD)-causing protein that drives the spread of alpha-synuclein, a key hallmark of the neurological condition.

Published in Nature Communications, the study reveals how the protein Aplp1 links to Lag3, a cell surface receptor that helps spread alpha-synuclein proteins to brain cells.

Currently one of the most prevalent neurodegenerative conditions, PD affects more than ten million people worldwide and is characterised by progressive, dysfunctional tremor, slowness and rigidity.

Previous studies have already shown that misfolded alpha-synuclein proteins journey from brain cell to brain cell, destroying those responsible for producing dopamine, a neurotransmitter, causing PD to progress through parthanatos, a programmed cell death.

Using Bristol Myers Squibb’s (BMS) Lag3 antibody drug, Opdualag (nivolumab/relatlimab), researchers used a line of genetically engineered mice that lacked either Aplp1 or Lag3, or both, to determine whether Aplp1 contributed to the spread of alpha-synuclein proteins.

In mice without Aplp1 and Lag3, results showed that cell absorption of the harmful alpha-synuclein was reduced by 90%.

Additionally, when injected with the Lag3 antibody, the drug blocked the interaction of Aplp1 and Lag3 in mice, stopping healthy brain cells from absorbing disease-causing alpha-synuclein clumps.

BMS’ Opdualag was approved by the US Food and Drug Administration in 2022 to treat adult patients with certain melanomas and could play a crucial role in preventing cells from absorbing alpha-synuclein.

Xiaobo Mao, associate professor of neurology, Johns Hopkins University School of Medicine and member of the Institute for Cell Engineering, commented: “We have a new way of understanding how alpha-synuclein contributes to the disease progression of PD.

“Our findings also suggest that targeting this interaction with drugs could significantly slow the progression of PD and other neurodegenerative diseases.”

Researchers intend to target Lag3 in Alzheimer’s disease, which binds with dementia-related tau protein with the same antibody, and are investigating how to prevent unhealthy cells from releasing disease-causing alpha-synuclein altogether.