Development of first selective inhibitor of LRRK2 mutation found in Parkinson’s disease is progress on road towards new therapy
This month is Parkinson’s awareness month. Following on from my recent interview (that you can read here & here) with Dr Todd Sherer of The Michael J. Fox Foundation for Parkinson’s Research, I was interested to read about progress being made on the road to towards targeted therapies.
The April 2011 issue of Nature Chemical Biology reports the development of a selective inhibitor of leucine-rich repeat kinase 2 (LRRK2), a gene that is mutated in some patients with Parkinson’s disease.
The team of researchers from Dana-Farber Cancer Institute, Harvard Medical School, University of Dundee, Scripps Research Institute and ActivX Biosciences applied a novel, screening strategy focused on selectively inhibiting LRRK2.
The result was the identification of LRRK2-IN-1, a novel analog that inhibits both wild-type and mutant LRRK2 kinase activity. The team confirmed the activity of LRRK2-IN-1 using human lymphoblastoid cells from a Parkinson’s disease patient with the LRRK2 mutation.
Unfortunately, LRRK2-IN-1 was unable to cross the blood-brain barrier, which means that it is not suitable for Parkinson’s disease. However, this research is progress on the road to LRRK2 inhibition and the development of a targeted therapy in the future.
Moving forwards Parkinsons’ researchers may wish to consider combining new small molecules with nanoparticles that are able to cross the blood-brain barrier; this may be the way to deliver targeted therapies to the brain.
Deng, X., Dzamko, N., Prescott, A., Davies, P., Liu, Q., Yang, Q., Lee, J., Patricelli, M., Nomanbhoy, T., Alessi, D., & Gray, N. (2011). Characterization of a selective inhibitor of the Parkinson’s disease kinase LRRK2 Nature Chemical Biology, 7 (4), 203-205 DOI: 10.1038/nCHeMBIO.538
