Promising “molecular tweezer” Parkinson’s therapy looks to human trials

New research published in the journal Nature Communications reveals a novel drug, designed to break up the aggregations of toxic proteins associated with Parkinson’s disease, can effectively slow the disease in mouse models. The researchers are now looking at moving toward human trials.

Molecular tweezers are novel compounds with the ability to essentially unpick abnormal clumps of proteins. In the case of Parkinson’s disease, neurodegeneration is thought to be caused by the aggregation of a protein called alpha-synuclein. These toxic protein clumps ultimately kill dopamine producing neurons leading to the motor degeneration commonly associated with the disease.

CLR01 is a type of molecular tweezer previously found to both prevent the alpha-synuclein aggregations from forming in the first place, and potentially dismantle clusters that have already formed. This newly published study builds on a growing body of diverse animal evidence to show CLR01 is safe and effective at slowing, and in some cases reversing, the pathological signs of Parkinson’s disease.

Perhaps the most important finding in this new study is the observation CLR01 may only be effective if administered at a particular point in the progression of the disease. The researchers administered the therapy to mice genetically modified to model Parkinson’s neurodegeneration, but CLR01 was ineffective when the animals were dosed at six months of age, and only partially effective when dosed at 18 months.

The study notes the most effective therapeutic window was when the animals were 12 months of age. This suggests CLR01 may only be effective if administered as a preventative therapy in the early stages of the disease.

“This is a very exciting piece of work showing that drug treatments can be developed to unpick toxic protein clusters to save neurons in models of Parkinson’s,” says lead author on the study, Richard Wade-Martins. “Our work is focused on developing new approaches to saving neurons when they start to lose function early on, but before they die later on in the condition.”

Beckie Port, from Parkinson’s UK, suggests this kind of novel molecular tweezer therapy is exciting and is urging for it to move into human trials as soon as possible.

“We desperately need treatments that protect brain cells in Parkinson’s,” says Port, who did not work on this new study. “These findings show that this innovative ‘molecular tweezer’ approach has exciting potential in the lab. We now need to take this therapy forward to test in clinical trials – only then will we know whether it can do the same in people with Parkinson’s.”

The new study was published in the journal Nature Communications.

Source: Oxford University

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