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Can an FDA-approved cancer drug help stop the progression of Parkinson's disease?

 
, medical expert
Last reviewed: 02.07.2025
 
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24 June 2024, 13:13

Parkinson's disease is a complex disorder that affects the function of the nervous system. Scientists are still trying to understand what changes occur in the brain in this condition and what actions can stop these changes.

One area of interest is to investigate the mechanisms that contribute to the accumulation of the protein alpha-synuclein in the brains of people with Parkinson's disease.

A study published in the journal Nature Communications found that two key proteins, Lag3 and Aplp1, interact to promote alpha-synuclein toxicity.

The researchers also found that using an antibody against Lag3 disrupted this protein interaction and helped stop neurodegeneration in mice.

If future studies confirm these findings, it could point to a potential way to stop the progression of Parkinson's disease.

Stopping the Progression of Parkinson's Disease: A New Approach

The researchers used mice to study the abnormal alpha-synuclein pathway. They confirmed that two key proteins, Aplp1 and Lag3, are involved in the process.

They found that the interaction between these two proteins promotes “pathological [alpha-synuclein] binding, internalization, trafficking, and toxicity.” These results also indicate that Aplp1 and the Aplp1-Lag3 interaction promote intercellular transmission of alpha-synuclein.

The study also found that genetically deleting Aplp1 and Lag3 helped preserve dopaminergic neurons—brain cells that release dopamine, a hormone whose production is disrupted in Parkinson's disease—and reversed behavioral deficits caused by preformed alpha-synuclein fibrils.

Study authors Xiaobo Mao, PhD, Ted M. Dawson, and Valina L. Dawson summarized the key findings of the study as follows:

“Our team at Johns Hopkins University has discovered that two proteins called Aplp1 and Lag3 play a major role in how Parkinson’s disease spreads throughout the brain. These proteins interact with each other and allow harmful clumps of another protein called alpha-synuclein to invade and kill healthy brain cells. Alpha-synuclein clumps are the hallmark of Parkinson’s disease and are responsible for the progressive loss of dopamine-producing neurons, leading to motor and cognitive impairment.”

Repositioning an Anti-Cancer Drug for Parkinson's Disease?

These data have specific clinical implications, as there is already an FDA-approved cancer drug that targets Lag3.

"An important discovery is that Lag3 is already the target of an FDA-approved cancer drug called nivolumab/relatlimab, which uses antibodies to block Lag3 activity," the study authors explained.

"By blocking the interaction between Aplp1 and Lag3, we found that an antibody against Lag3 could prevent the spread of alpha-synuclein clumps in mouse models of Parkinson's disease. This suggests that repositioning this FDA-approved drug could potentially slow or stop the progression of Parkinson's disease in humans," they explained.

Future research

This study has some key limitations, mainly that testing something in mice is different from testing it in people.

The researchers are also limited by the nature of their work, the procedures used, and the effectiveness of the type of mice used in this study.

The study authors also acknowledge that Aplp1 may be facilitating Lag3 action through something other than direct interaction, so more research is needed in this area. They also want to delve deeper into the physiological roles of Aplp1 and Lag3 and how these proteins may interact with other cell types.

The Impact of Parkinson's Disease on Health

Parkinson's disease affects the brain and movement. One of the characteristic changes in the brain in Parkinson's disease is the presence of Lewy bodies.

These Lewy bodies are clumps of the protein alpha-synuclein that build up inside brain cells. People with Parkinson's disease may experience movement difficulties, such as tremors, loss of balance, and changes in gait. They may also have problems with memory or concentration.

There is currently no cure for Parkinson's disease, so treatment is mainly aimed at relieving symptoms. This may include therapy to help with movement and speech, dietary changes, and the use of medications to help manage movement problems.

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