Tiny variations in DNA are associated with approximately 20% of Parkinson's cases. One of the most common genetic risk factor occurs in a region of DNA called the GBA gene. This sequence of DNA provides the instructions for producing an enzyme - called GCase - which cells use to break down and dispose of waste and unwanted products in cells.

This week researchers at the Northwestern University Feinberg School of Medicine published a report identifying a small molecule called S-181 which they found to be an activator of GCase activity. The interesting aspect of their research, however, is that S-181 not only improved GCase activity in cells with GBA genetic variations, but also enhanced the GCase function in cells with different Parkinson's-associated genetic risk factors (such as the LRRK2 and PARKIN genes) as well as in cells from people with spontaneous Parkinson's (those cases with no obvious genetic influence). S-181 was also found to rescue a mouse model of GBA-associated Parkinson's.

The findings of this new study suggest that enhancing GCase activity may be beneficial in a broader cohort of the Parkinson's-affected community, not just those affected with the GBA genetic variants. The researchers have, on the strength of their research, now started a biotech company called Surmount Bio in order to further develop this new drug and take it forward for clinical testing in people with Parkinson's.

This new drug is targeting the same biological pathway as another drug - Ambroxol. This clinically available medication - which is used for the treatment of respiratory conditions - has also been found to enhance GCase activity and is now being re-purposed in Parkinson's, under the Linked Clinical Trials programme by The Cure Parkinson's Trust, Van Andel Institute, and the John Black Foundation. The Phase II results of this clinical trial will be published shortly.

This article appeared in 

See the report abstract: https://stm.sciencemag.org/content/11/514/eaau6870