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Study sheds light on immunotherapy treatment for ALS

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Washington | August 6, 2023 6:45:16 PM IST
A type of monoclonal antibody that has already been tested in cancer may be a viable treatment for amyotrophic lateral sclerosis, or ALS, a fatal neurological disease.

Researchers from Oregon Health & Science University led the study, which was published in the Proceedings of the National Academy of Sciences.

The study, which used a mouse model and was confirmed in ALS-affected human brain tissue donated after death, demonstrated for the first time that altering immune cells can slow the progression of the disease.

Researchers used a high-throughput screening technique to identify a specific type of protein produced on immune cells in ALS patients' brains and spinal cords, contradicting previous findings that suggested immune cells may play a role in the disease.

The protein, known as alpha-5 integrin, was implicated by researchers.

When we blocked its expression in mice, we were able to slow down the disease, said senior author Bahareh Ajami, PhD, assistant professor of molecular microbiology and immunology and behavioural neuroscience at the OHSU School of Medicine. We hope that it will get to the clinic very soon.

The team used a monoclonal antibody targeting a5 integrin, which had already been developed and used in treating certain forms of cancer. This means that its already undergone extensive safety studies to achieve approval through the Food and Drug Administration.

Hopefully, it could be repurposed, she said.

Using postmortem tissue from 139 brains donated for research, scientists confirmed the presence of a5 integrin within areas of the brain associated with motor function. Specifically, they found a5 integrin expressed by microglial cells and macrophages in blood cells associated with the immune system to be highly pronounced in the spinal cord, motor cortex and peripheral nerves during ALS.

They then tested the monoclonal antibody targeting a5 integrin in mice genetically predisposed to carry ALS and found that it protected motor function, delayed disease progression and increased mouse survival.

We couldnt believe they were doing so much better, Ajami said.

Ajami, whose lab focuses on modulating the immune system to treat neurodegenerative diseases, said the study suggests the potential for applying immunotherapies to ALS as its already used in cancer and more recently through the use of monoclonal antibodies targeting Alzheimers disease.

At this point, we cannot say its a cure but its a very interesting start, she said. It may be similar to what immunotherapy did for cancer or will do for Alzheimers by targeting immune cells.

Ajami previously studied microglia in ALS. The studys first author, Aude Chiot, Ph.D., of OHSU previously identified peripheral nerve macrophages as therapeutic targets in ALS mice.

Todays study complements their previous work by identifying a targetable protein in these cells.

Ajami said the next step in the research will be to develop dose-response studies in the mouse model, and she ultimately hopes to see it progress to the point that it can be used to treat people with ALS. (ANI)

 
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