Cells, energy control and Parkinson’s: The role of PINK1 and Parkin

Dr. Miratul Muqit

Abstract

My research is directed at defining key pathways in cells that are linked to the development of Parkinson’s and harnessing this knowledge to generate new ideas to prevent and treat the condition. Major advances in genetics have provided clues as to the key molecules that control such pathways however there remain fundamental gaps in our understanding of how these genes function in cells. In my laboratory we have been focused on the PINK1 and Parkin genes that represent the commonest genetic cause of Parkinson’s in patients under the age of 45.

In my presentation I will discuss how the PINK1 and Parkin genes cooperate very closely in cells to protect us against damage to ‘mitochondria’ which are energy-producing centres of our cells. Our work has spanned very basic experiments in cells, but we have recently obtained very strong evidence in humans of the relevance of the PINK1-Parkin pathway to Parkinson’s.

Our work provides a framework for Clinicians to translate our knowledge and test our findings in patients both for the development of better diagnostics and therapies against Parkinson’s.

Bench to bedside Parkinson’s Research

Dr. Esther Sammler

Abstract

The greatest unmet need in Parkinson’s are treatments that slow the relentless progression of its symptoms. The discovery of genetic changes in different genes that cause Parkinson’s have prompted new therapeutic approaches. LRRK2 is the most frequently mutated gene in Parkinson’s and LRRK2 inhibitor drugs have recently entered early clinical trial stages. However, many questions remain including markers of disease progression, biochemical markers for LRRK2 activation status and biomarkers for drug target engagement. These biomarkers will be necessary to confirm patient subgroups with high LRRK2 activity that might receive greater benefits from these therapies and ensure that the drug has the desired effect on the pathway targeted.

My talk will focus on a test that we have developed to measure LRRK2 activity in human peripheral blood and I will show very exciting data demonstrating the usefulness of this test.

For people interested in participating in research, I will also briefly mention a translational research project of mine (involving donating a blood sample) that will soon launch in the East and South East of Scotland.

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!