Fall / Winter 2024 | Research 7
Leveraging LRRK2 Advances into Better Drugs Faster
By Jen Fisher Wilson
Dario Alessi , PhD , leader of the LRRK2 Investigative Therapeutics Exchange , received MJFF ’ s 2023 Robert A . Pritzker Prize for Leadership in Parkinson ’ s Research for his contributions to the field and commitment to mentoring the next generation of Parkinson ’ s scientists .
In the 20 years since researchers linked LRRK2 gene mutations to Parkinson ’ s disease ( PD ), research into this previously little-studied gene has exploded — unlocking critical insights into the biology that underlies PD .
Biochemist Dario Alessi , PhD , at the University of Dundee , UK , has been involved since the beginning , after encountering the first papers describing the mutations in 2004 . The finding fascinated him immediately , he said , because LRRK2 encoded a protein kinase , a type of enzyme that was his specialty . “ I thought if you could study this , it might yield new ideas about how to treat and even prevent Parkinson ’ s ,” he said .
He wasn ’ t wrong . In large part to MJFF ’ s committed support , research on LRRK2 has expanded . Today , several drugs targeting LRRK2 are in clinical trials , including a leading LRRK2 therapy that is being evaluated in people with and without LRRK2 mutations .
Now , Alessi and his colleague Esther Sammler , MD , PhD — a neurologist at University of Dundee who also has a long history with
LRRK2 — are helming a major new MJFF initiative devoted entirely to LRRK2 . The LRRK2 Investigative Therapeutics Exchange ( LITE ) commits tens of millions of dollars to de-risking and rapidly expediting new LRRK2 therapeutic strategies , ensuring novel approaches to targeting LRRK2 advance quickly into translational studies .
These translational studies help bridge the gap between academia and industry , said Shalini Padmanabhan , PhD , MJFF ’ s head of translational research . By providing evidence about which approaches hold the most promise , “ decisionmaking around therapeutic development is faster and more informed ,” she said , “ and investments by drug developers are less risky .”
LITE ’ s benefits are expected to include important new learnings about the molecular underpinnings of Parkinson ’ s and tools for clinical trials , especially novel biomarkers for LRRK2 .
Ultimately , the whole purpose of LITE , Padmanabhan said , is to deliver new medicines to people with PD in the fastest way possible . “ It is ,” she said , “ as always , our most urgent mission .”