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Johns Hopkins Medicine researchers have unveiled a promising avenue in the fight against Parkinson's disease using an FDA-approved cancer drug.

The research centers on Aplp1, a cell surface protein implicated in the propagation of alpha-synuclein proteins, which are notorious for their role in Parkinson's disease pathology. By linking with Lag3, another cell surface receptor, Aplp1 facilitates the transfer of harmful alpha-synuclein proteins between brain cells, exacerbating the disease.

Lead researcher Xiaobo Mao, Ph.D., from the Johns Hopkins University School of Medicine, explained the significance of these findings, saying: "Now that we know how Aplp1 and Lag3 interact, we have a new way of understanding how alpha-synuclein contributes to the disease progression of Parkinson's disease."

"Our findings also suggest that targeting this interaction with drugs could significantly slow the progression of Parkinson's disease and other neurodegenerative diseases," Mao added, Neuroscience News reported.

The study, co-led by Ted Dawson, M.D., Ph.D., and colleagues at the Johns Hopkins Institute for Cell Engineering, builds upon earlier research highlighting Lag3's role in binding alpha-synuclein proteins. Recent experiments involving genetically engineered mice lacking Aplp1 and Lag3 demonstrated a remarkable 90% reduction in the absorption of disease-causing alpha-synuclein proteins by brain cells.

Moreover, injecting mice with an antibody targeting Lag3, specifically nivolumab/relatlimab, an FDA-approved drug for cancer treatment, effectively disrupted the Aplp1-Lag3 interaction. This intervention prevented further spread of alpha-synuclein seeds in mouse models, offering better efficacy than depleting Lag3 alone.

"The anti-Lag3 antibody was successful in preventing further spread of alpha-synuclein seeds in the mouse models and exhibited better efficacy than Lag3-depletion because of Aplp1's close association with Lag3," Ted Dawson explained.

Looking ahead, the researchers plan to conduct trials using the Lag3 antibody in mouse models of Parkinson's and Alzheimer's disease. They also aim to explore strategies to inhibit the release of disease-causing alpha-synuclein by unhealthy cells, further advancing therapeutic options.

The promising results of this study pave the way for novel treatments that could alter the trajectory of Parkinson's disease and potentially other neurodegenerative disorders that currently lack effective therapies.

The study was published in Nature Communications on May 31.