In the case of Parkinson's Disease (PD), mutations in the gene LRRK2 have been linked to early onset of disease. The most common is the so-called G2019S mutation. While the average person has a 1-2% chance of developing PD, the risk for someone with the G2019S mutation is much higher and increases with age. A person who inherits this mutation from either parent has a 28% chance of developing PD by the age of 59, 51% by the age of 69 and 74% by the age of 79. In addition, up to 40% of people of North African Arab ancestry and 25% of Ashkenazi Jewish people with PD have this mutation.
Most of the research in the LRRK2 field has been focused on developing non-mutant specific inhibitors to treat all PD patients with a single drug. However, Acelot's JPS-powered PD program is designed to take advantage of the structural differences between wild-type LRRK2 and the G2019S mutant in order to find mutant specific inhibitors.
Given our current understanding that this mutation lies in the activation loop of the kinase, the onset of the disease is relatively predictable with age, and the tight local geographic distribution of the affected population makes G2019S mutant LRRK2 an attractive target from the point of view of preclinical and clinical studies.
To date, Acelot has discovered previously unidentified LRRK2 inhibitors, one of whom shows orders of magnitude stronger binding to the G2019S mutation than to the wild-type. This will be a good starting point for further screening and optimization on the way to novel mutant-specific lead compounds.
Please contact us if you are interested in partnering for this project.