Dr. Arjan Kortholt of the research group Cell Biochemistry (Groningen Biomolecular Sciences and Biotechnology Institute, GBB) has been awarded a new grant by the Michael J. Fox Foundation (MJFF) to characterize and optimize inhibitors for LRRK2-mediated Parkinson's disease. In the first phase €100,000 is awarded that following an assessment after one year substantial funding may become available for the next phase.
Mutation in LRRK2 are the most frequent cause of late-onset Parkinson’s disease.
Although the biological function of the multi-domain LRRK2 protein is not fully understood, it is clear that the pathogenic LRRK2 mutations result in hyper-activity of the protein. Therefore inhibitors of LRRK2 have the potential of being used as therapeutic drugs or to prevent Parkinson's disease.
arious classes of LRRK2 kinase inhibitors with various shortcomings have been identified. The main target of these inhibitors is the LRRK2 kinase domain. However, the optimization of this class of drugs is hampered by the lack of three dimensional structures of the LRRK2 kinase domain bound to the compound. Although a large number of academic and industrial laboratories have attempted to solve the three-dimensional structure of the kinase domain of LRRK2, no such structure has been described. The objective of this project is to develop a LRRK2 structural reagent to shed light on compounds which bind to kinase domain. Such a structural surrogate probe for LRRK2 kinase will accelerate discovery, characterization and optimization of novel inhibitors and the progression of inhibitors to more drug-like molecules will be accelerated.
This project is a collaboration between Merck Research Laboratories (Boston MA) and the MJFF structure and function consortium.
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