Alpha-synuclein is a protein which is abundant in the brain and throughout the body. It carries important functions, in relation to communication between neurons for example. When misfolded however, it becomes toxic to neurons and is a key pathological culprit in Parkinson’s. It is therefore an important target for disease modification. Immunotherapy in Parkinson's attempts to use immune cells, and specifically the antibodies they generate, to target misfolded alpha-synuclein to inactivate it. 

BIIB054 is a human-derived antibody being developed by Biogen Inc. with high selectivity for the toxic, misfolded form of alpha-synuclein, and preclinical studies have shown BIIB054 reduces the spread of misfolded alpha-synuclein and limits the damage it normally does to neurons.

Researchers first derived the antibodies which bind to alpha-synuclein, from cloned B lymphocytes, which are a specific type of white blood cell obtained from healthy elderly donors. These specific BIIB054 antibodies were selected on the basis of their ability to bind toxic, misfolded alpha-synuclein found in postmortem brain samples obtained from individuals with Parkinson’s and Lewy Body Dementia. Having established this high selectivity, BIIB054 antibodies were taken through to a series of animal experiments. The researchers first produced misfolded alpha-synuclein. Then, they infused the animals with BIIB054 or an ineffective antibody as a control. After BIIB054 infusions were begun, the misfolded alpha-synuclein was injected directly into the striatum, a key movement area rich in dopamine neurons. They found that BIIB054 administered weekly, significantly delayed the onset of movement symptoms. The researchers then tested whether BIIB054 could stop the spread of alpha-synuclein between adjacent neurons. Prior and continuous administration of BIIB054 caused a significant reduction in the overall amount of misfolded alpha-synuclein found in these animals and also improved some of the movement problems. They also found that BIIB054 reduced the loss of dopamine transporters (DAT) normally found on dopamine neurons and measured by DAT scans.

A multicentre Phase 2 clinical trial has now begun recruiting to evaluate the dose-related safety of BIIB054 for the treatment of Parkinson’s. This work demonstrates the potential of BIIB054 as a highly selective immunotherapy which may modify the course of Parkinson’s, and create more data on this antibody for further evaluation.

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