Treatment with a drug called CLR01 improved balance and movement coordination in mice with early stage Parkinson’s disease, according to results of a new preclinical study.
Researchers said CLR01 acts by decreasing the amount of unstable alpha-synuclein, one of the two forms of the protein existing in the brain, and the one that is believed to be associated with the development of Parkinson’s disease.
The study “A Molecular Tweezer Ameliorates Motor Deficits in Mice Overexpressing α-Synuclein” was published in the journal Neurotherapeutics.
CLR01 works as a molecular tweezer – its “C” shape allows it to wrap around chains of lysine (an amino acid that is present in nearly all proteins) and disrupt the formation of protein clumps that will affect the normal functioning of neurons. Previous research had shown that treatment with CLR01 avoided the formation of alpha-synuclein aggregates in zebrafish and its toxic effects in brain cells without affecting the surrounding healthy cells.
According to a press release from UCLA, where the research was performed, there are two forms of toxic alpha-synuclein in the brain. One of the forms clumps together leading to the formation of protein aggregates, whereas the second form is unstable, more toxic and harder to trace. The second form is believed to be the one that most affects neuronal activity in Parkinson’s disease.
In the study, researchers treated young male mice with early stage Parkinson’s and carrying the gene for human alpha-synuclein, with CLR01 and analyzed the animals’ motor behavior and protein in the brain.
Results showed that direct treatment with CLR01 within the brain for 28 days improved motor coordination and caused a significant decrease of the unstable form of alpha-synuclein in the striatum (a brain region that helps coordinate movement).
Importantly, this treatment did not affect the formation of alpha-synuclein aggregates (composed of the other form of the protein), showing that CLR01 specifically targets the most dangerous form of this protein.
“The data support further development of molecular tweezers as therapeutic agents for [diseases similar to Parkinson’s disease],” researchers wrote.
The team now wants to develop CLR01 delivery to the brain and further investigate the effects of this drug and how it works in the body to advance its transition to human clinical trials approved by the U.S. Food and Drug Administration.