LRRK2 in Parkinson’s

Prof. Dario Alessi

Abstract

My laboratory is focused on deciphering the molecular causes of Parkinson’s. We believe that if we can comprehend what causes Parkinson’s, this will enable Researchers, Clinicians and Pharmaceutical Companies to work together to develop better ways to diagnose and treat the condition in the future. The approach we are taking is to study how mutations in certain genes cause Parkinson’s. One of the genes that we are working most on is called “LRRK2”. The LRRK2 gene is one of the most commonly mutated genes that causes familial inherited Parkinson’s. The LRRK2 gene encodes for a protein that is called the “LRRK2 enzyme”. Important research by our laboratory and others has shown that Parkinson’s mutations activate the LRRK2 enzyme.

This has led to the suggestions that drugs that target the LRRK2 enzyme could be developed for the better treatment of Parkinson’s. Excitingly, a company called Denali, based in San Francisco has recently launched the first clinical trials to test this idea. Several other companies are expected to initiate LRRK2 Parkinson’s trials soon.

These new drugs have the potential to slow down the progression of Parkinson’s.  

I will talk about the highlights of our recent research that have led to the discovery of how the LRRK2 enzyme works to control the activity of another set of enzymes called Rab.  I will describe recent work that has resulted in the discovery that mutation in several other genes that cause Parkinson’s, are also excitingly linked to the LRRK2 and Rab enzymes. Our work is revealing that LRRK2 is at the centre of a physiological network which is critical to understanding Parkinson’s. I will explain that with this increasing knowledge of the genetics and biology underlining Parkinson’s, I feel optimistic.

I believe that it is not unrealistic that with continued and expanded research efforts, major strides towards better treating Parkinson’s disease can be made in the coming years. Patient’s support and involvement in research is vital for success!

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