In Parkinson’s, a protein called alpha-synuclein which is abundant in nerve cells, begins clumping together (or aggregating) and it is believed that this process could be toxic. Anle138b is a small molecule that has been developed, by the German biotech company MODAG, to inhibit alpha-synuclein aggregation; and it is hoped that this treatment will slow-down or halt the progression of Parkinson’s.
Alpha-synuclein is considered “public enemy number one” in Parkinson’s research. We have known since the 1990s that the aggregation of this protein inside of neurons is one of the characteristic features of the Parkinson’s brain. This aggregation is believed to be toxic and as a result there are currently many clinical trials underway targeting alpha-synuclein and trying to remove the aggregates.
One experimental approach to reduce levels of alpha-synuclein in the Parkinson’s brain involve antibodies. Antibodies act as red flags for immune cells in the body. They label foreign substances or rogue proteins that need to be removed. Using the immune system to recognise the toxic form of alpha-synuclein is an important area of research – it is called ‘immunotherapy’. One of the acknowledged limitations of the immune therapy approach however is the low amount of antibody that actually accesses the brain.
This is where small molecules like anle138b might have an advantage. Anle138b is taken by mouth, easily enters the brain, and preclinical research indicates that it is very good at reducing levels of aggregated alpha synuclein inside cells. The reduction of alpha-synuclein in the brain has been reported to reverse Parkinson’s-like motor symptoms in animal models.
Following the positive preclinical data and initial phase 1 testing, MODAG is now conducting a second phase 1 study of anle138b in people with Parkinson’s. This trial is being conducted in the UK at Nottingham University Hospital. It involves testing different doses of the drug in 24 participants with mild to moderate Parkinson’s.
Cure Parkinson’s continues to support this promising area of research.
Read more about the alpha-synuclein drug pipeline in Deputy Director of Research, Dr Simon Stott’s blog post:
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