We’ve discovered an important clue to how Parkinson’s disease spreads in the brain. And how to treat it

• One of the key parts of the discovery is the Lag3 protein.

• Treatments based on antibodies to this protein may help us in this fight.

Neurodegenerative diseases pose a challenge to those who study them. Due to the complexity of the brain and the difficulty of studying it using invasive methods. This is why understanding the biochemical mechanisms underlying diseases such as Parkinson’s is so important.

Converted drug. A new study has opened a new path in the study of Parkinson’s disease and, especially, ways to treat it. The research could lead us to turn a drug approved to fight cancer into a treatment for this neurodegenerative disease.

The drug in question is nivolumab/relatlimab. It is a drug developed to treat melanoma, a skin cancer that interacts with a protein called Lag3, which is located on the surface of our cells.

Despite this, research on this new application has only shown promising results in mice so far. That is, even though the use has already been approved, there is a long way to go.

Alpha-synuclein. One of the keys to the discovery is a protein called α-synuclein. When errors occur in the folding of α-synuclein, the proteins tend to accumulate, forming clumps. These protein accumulations are often considered the “hallmark” of Parkinson’s disease.

Lag3 and Application1. Other players involved are the proteins Lag3 and Aplp1. The study of these proteins, explains the team responsible, has shown how, through their interaction, α-synuclein can reach our brain cells.

“Now that we know how Lag3 and Aplp1 interact, we have a new way to understand how alpha-synuclein contributes to the progression of Parkinson’s disease,” Xiaobo Mao, a member of the team responsible for the study, explained in a press release.

Details of the work carried out were published in an article in the journal. Natural communications.

Approved treatment. The team emphasizes the positive implications of their discovery: we already have a drug that interacts with these molecules and can therefore block the pathway of alpha-synuclein molecules. This is denivolumab/relatlimab, a drug based on antibodies to the Lag3 protein.

Preliminary results suggest that this might abolish this protein by preventing it from binding to Aplp1 and thereby preventing these proteins from opening the cell wall “door” to α-synuclein.

The treatment was approved by drug regulators in the US and Europe in 2022. That should make it easier for the drug to be re-approved (as has happened with Ozempic and others), but it must first be shown to be effective in clinical trials with people.

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