Promising results from APDA-funded LRRK2 research

Promising results from APDA-funded LRRK2 research

On July 25, 2018, the APDA Center for Advanced Research at the University of Pittsburgh, led by the Center’s Director (and APDA Scientific Advisory Board member), Dr. J. Timothy Greenamyre, published results of a study highlighting the role of Leucine-rich Repeat Kinase (LRRK2) in the development of Parkinson’s disease. LRRK2 is known to be mutated in a small percentage of people with Parkinson’s disease, about 1-2% of all people with Parkinson’s disease, although much higher in certain populations, such as Ashkenazi Jews and North African Berbers.

LRRK2 is an enzyme, a protein used by the body to help bring about a biochemical reaction. Specifically, it is a kinase, an enzyme which adds phosphate groups onto other proteins. Mutations in LRRK2 that cause Parkinson’s disease increase the kinase activity of LRRK2.

Dr. Greenamyre’s work used a technique known as a proximity ligation assay which allows for the detection of very small amounts of interactions between proteins or modifications of proteins in a highly specific and sensitive way. Using this technique, the study set out to visualize the activation of LRRK2 within cells.

What was surprising about the results of Dr. Greenamyre’s work was that Parkinson’s patients who did not have LRRK2 mutations also had increased activity of LRRK2. This means that LRRK2 activation is an important step in the development of Parkinson’s disease and if the activation does not come via a mutation, it may come as a result of other biochemical changes in the cell. It also means that medications that reduce LRRK2 activation could help a large swath of patients with Parkinson’s disease and not just people with a LRRK2 mutation. Small molecules that inhibit LRRK2 activity have been tested in Phase 1 trials and continue to be under development.

APDA continues to fund this and other promising science involving understanding the role of LRRK2 in Parkinson’s disease, including the work of Dr. Yulan Xiong, Dr. Ian Martin and Dr. Fabio Demontis. Stay tuned for our upcoming announcement of our 2018-2019 grantees to learn more about the exciting and important research we are funding.

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