Denali Therapeutics has announced positive clinical results from their LRRK2 inhibitor programme and their advance to a Phase 1b trial in Parkinson’s patients with and without a genetic LRRK2 mutation.

Genetic mutations (or variants) within the LRRK2 gene are recognised as being some of the most common with regards to increasing ones risk of developing Parkinson’s. But despite being one of the ‘most common’ genetic risk factors, variants in the LRRK2 gene are only present in approximately 1-2% of all cases of Parkinson’s. However, in a recent new report it is suggested that independent of any genetic mutations, LRRK2 may actually play a role in idiopathic (or spontaneous) forms of Parkinson’s, which means that the treatments being developed for LRRK2 may not be limited to those individuals with particular LRRK2 genetic variations and could be beneficial for a wider section of the PD community.

In this recent study, Denali Therapeutics DNL201 molecule was trialled in more than 100 healthy subjects, including healthy elderly subjects, received either single or multiple ascending doses or placebo. Based on the clinical data from this study, Denali intends to advance DNL201 into a Phase 1b clinical study in Parkinson’s disease patients with and without a genetic LRRK2 mutation by year-end 2018. Detailed clinical data from the Phase 1 study with DNL201 will be presented at a future medical conference.

“We conclude from this clinical trial that DNL201 was able to achieve the targeted level of LRRK2 inhibition at doses that were safe and well tolerated. We are pleased that the trial was a success in all these key measures. The trial data give us confidence to proceed with further clinical testing in Parkinson’s patients and provide a solid basis for selection of the optimal dose for future clinical trials in patients,” said Carole Ho, M.D., Chief Medical Officer.

“We are leading the way in testing LRRK2 inhibitors in humans with the goal of bringing a disease modifying therapeutic to patients suffering from Parkinson’s disease," said Ryan Watts, Ph.D., CEO. We are also encouraged to see mounting evidence supporting a role of LRRK2 inhibition in the broader sporadic Parkinson’s disease population, in addition to Parkinson’s disease genetically associated with a LRRK2 mutation.

A Phase 1 dose escalation study with DNL151, a second small molecule inhibitor of LRRK2, is ongoing in the Netherlands.

Read more about the Denali trial here:

Read more about LRRK2 and Parkinson's: Science of Parkinson's Disease