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▎The content team editor of WuXi AppTec.
Neurodegenerative diseases such as Alzheimer’s disease (AD) and Parkinson’s disease (PD) affect the lives of tens of millions of elderly people around the world.
One of the characteristics of these diseases is usually in the brain.
There will be abnormal protein deposits.

Therefore, one strategy for pharmaceutical companies to treat such diseases is to develop antibodies that target them to help clear these protein deposits.

However, the effect of most antibody therapies in clinical trials is not significant.
Recently, a research team at The Scripps Research Institute has an unexpected discovery: antibody therapies designed to remove protein deposits may instead It triggers the inflammatory response of immune cells, thereby weakening the effect of antibody therapy.

▲Brain cells differentiated from human stem cells, green are microglia and red are dopaminergic neurons (Image courtesy of the Lipton laboratory at Scripps Research).
In this study, scientists made human stem cells differentiate into microglia , And then test whether α-synuclein oligomers can stimulate their inflammatory response.

Surprisingly, when the researchers added a monoclonal antibody against alpha-synuclein to the culture medium, it stimulated a stronger inflammatory response.

In the brains of Parkinson’s disease patients, β-amyloid deposits are often clustered with α-synuclein deposits, and in Alzheimer’s disease patients, α-synuclein deposits often appear in amyloid deposits.
in.

In this study, the scientists added β-amyloid oligomers to the culture medium to simulate what happens in the brains of patients.

They found that β-amyloid protein can exacerbate inflammation, and the addition of anti-amyloid antibodies can further aggravate inflammation! Further studies have shown that antibodies themselves do not cause human microglia to produce an inflammatory response, but the complexes produced by the binding of antibodies to their targets can stimulate the inflammatory response of microglia.

Inflammation is considered to be one of the important reasons leading to the death of nerve cells in the brain of patients with neurodegenerative diseases.

▲The co-senior author of this study, Dr.
Stuart Lipton (photo source: Scripps Institute official website) "Our findings provide a possible explanation for the poor effectiveness of current antibody therapies in the treatment of neurodegenerative diseases.

" The study's co-senior author, Dr.
Stuart Lipton, a professor in the Department of Molecular Medicine at the Scripps Research Institute, said that the inflammatory response observed in the study may offset the beneficial effects of antibody therapy.

Dr.
Lipton said that he and his colleagues have developed an experimental drug that can reverse this inflammatory response and may restore the benefits of antibody therapy to the human brain.

The research plan was published in the Proceedings of the National Academy of Sciences (PNAS).

Reference: [1] Experimental antibody therapies for Parkinson's and Alzheimer's may cause harmful inflammation.
Retrieved April 2, 2021, frominflammation.
html[2] Trudler et al.
(2021) Soluble α-synuclein–antibodycomplexes activate the NLRP3 inflammasome in hiPSC-derived microglia.
PNAS, doi:10.
1073/pnas.
2025847118 Note: This article aims to introduce medical and health research progress, not Recommended treatment plan.

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