Promising Parkinson’s Drug Moves Forward With Help From Michael J. Fox Foundation
The Michael J. Fox Foundation (MJFF) for Parkinson’s research spearheaded the LRRK2 Safety Initiative by bringing together three companies working on developing LRRK2 drugs for Parkinson's. The Initiative demonstrated that LRRK2 inhibitors were safe for human testing, thus making it worthwhile to continue ongoing financial investment and research.
Earlier forms of the new Parkinson’s disease (PD) drug were almost abandoned by global drug companies Pfizer, Merck, and Genentech. All three were ready to stop funding development of their drugs. The MJFF LRRK2 Safety Initiative supported collaboration amongst the companies so as to better understand any clinical failures of the original molecules.2
Denali Therapeutics, a San Francisco biotech, is a new company that was formed by scientists from Genentech who licensed the Genentech drug molecule. It is testing a new drug that targets the LRRK2 protein that plays a role in the waste-disposal system of a cell.2
LRRK2 in Parkinson’s
Over one million people in the US have Parkinson’s, but only 3-4% have the familial form associated with a mutation in the LRRK2 gene. LRRK2 stands for leucine-rich repeat kinase. More than a decade ago, scientists recognized that changes in the activity of the LRRK2 protein are associated with the hereditary form of Parkinson’s disease and may play a role in the development of other types of Parkinson’s even without the gene mutation.2,3
LRRK2 inhibitor in human testing
The LRRK2 protein is a priority target for creating a therapy to stop or slow the progression of Parkinson’s. Mutations in the LRRK2 gene cause heightened activity of the LRRK2 protein kinase, which modifies other proteins. Researchers are investigating whether lowering the activity level with drug inhibitors could protect brain cells.1,4
The study is now in a human testing phase with volunteers who are not Parkinson’s patients. By using human subjects who are not diagnosed with Parkinson’s, researchers are looking to answer two significant questions: (1) Does the drug block the LRRK2 sufficiently so that it has the potential to be effective in Parkinson’s patients?, and (2) Can it work without some previously noted side effects found in some of the earlier formulations, particularly affecting blood pressure and the lungs?2
The Denali study is presenting its first human data to Parkinson’s researchers at the MJFF annual scientific conference. The Phase I study is looking at the drug in healthy volunteers.1 Early findings suggest that the new drug successfully and safely blocks LRRK2 activity. Future phases will investigate LRRK2 inhibitor testing in Parkinson’s patients.
The MJFF’s role is pivotal in bringing together this consortium to study the safety initiatives of this new therapy. It has encouraged the pharmaceutical industry to be patient-focused. Collaboration in success and in failure can lead to the sharing of information that when analyzed together results in therapeutic benefits. “Research is a business, and it’s unfortunately often competitive,” said MJFF CEO Todd Sherer, PhD. He praised the collaborating companies for putting people with Parkinson’s first as they continue drug development projects through clinical testing and application for the those living with Parkinson’s disease.4
Denali is the first company to carry out clinical trials with LRRK2 inhibitors for treating PD. The next phase in clinical testing will include people with Parkinson’s disease with and without the genetic LRRK2 mutation. The next phase will include a global recruitment program to identify people with Parkinson’s who have the gene mutation to participate in future clinical trials.5
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