Emerging Research: Immunotherapy to Synuclein-Propagation Hypothesis

Reviewed by: HU Medical Review Board | Last reviewed: March 2017 | Last updated: March 2021

Immunotherapy can either be a type of treatment that aims to boost the body’s own immune system to fight disease processes, or immunotherapy reagents, such as antibodies, can be developed in the lab and directly administered to patients. One of the areas of research in Parkinson’s disease (PD) treatment is the use of immunotherapy to target the protein alpha-synuclein.

Alpha-synuclein and the development of Parkinson’s disease

Alpha-synuclein is believed to play a significant role in the development of PD. The accumulations of alpha-synuclein into clumps (also called Lewy bodies) are a key characteristic of the disease and cause dysfunction in the nerve cells. PD may progress by the secretion of abnormal forms of alpha-synuclein from one neuron to the next. This is called the propagation hypothesis. Studies have shown that the progressive spread of Lewy bodies correlates with the clinical progression of PD. These findings suggest that the spread of Lewy bodies drives the disease progression, leading researchers to propose that stopping the spread of alpha-synuclein might stop the disease progression.1-3

How immunotherapy works on alpha-synuclein

Immunotherapy uses the existing processes of the immune system to stop or treat a disease. The immune system uses antibodies to identify and destroy threats, which could be a virus, a toxin, or in the case of PD, the protein alpha-synuclein.

Antibodies have been identified through research that can bind to alpha-synuclein and neutralize it. Researchers hope that this process will slow the progression of PD and prevent the spread of the disease from one area of the brain to another. There is currently no known disease-modifying treatment for PD – one that slows the worsening of the disease. If this immunotherapy targeting alpha-synuclein works, the treatment should delay the appearance of symptoms and reduce the severity of symptoms.2

Status of research

Studies to date have been encouraging that alpha-synuclein is an effective target for immunotherapy; however, there are still several hurdles and challenges. Alpha-synuclein has normal functions within the cells of the body, and immunotherapy should not interfere with its normal functioning. Many of the research studies to date have worked with mouse models and are not yet at the human testing stage. Also, researchers are studying how best to deliver the antibodies to penetrate the blood-brain barrier. 2,3

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