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Leucine-rich repeat kinase 2 (or LRRK2) is a large, multi function protein that is associated with Parkinson’s. People with genetic variations in the region of DNA that provides the instructions for making LRRK2 protein have a higher risk of developing the condition.
In many cases of Parkinson’s, LRRK2 can become hyperactive. Researchers and biotech companies have been striving to identify drug-like molecules that can dampen down this hyperactivity in the hope of slowing down the progression of Parkinson’s.
One of the leading biotech firms in this area of research is Denali Therapeutics, and recently the company has provided some updates on their progress.
In today’s post, we will discuss what LRRK2 is, we will look at what Denali have achieved thus far, and we will review what the company has recently announced.
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A presentation was given at the UBS 2021 Global Healthcare Virtual Conference this week by representatives from Denali Therapeutics.
The slide deck (which can be found here on the company’s website) touched on multiple lines of active research for the company, including their active clinical trial programs:
- DNL310 (ETV:iduronate-2-sulfatase (IDS) for Hunter syndrome), which has expanded testing in Phase 1/2 based on positive interim data
- DNL343 (EIF2B activator indicated for ALS), which has had positive interim Phase 1 data, and the company is planning a Phase 1b study in ALS (Click here to read a recent SoPD post on EIF2B activation)
- DNL788 (RIPK1 inhibitor targeted at ALS, Alzheimer’s, & Multiple Sclerosis … I’m really curious, why not PD?!?), which is in ongoing Phase 1 studies in healthy volunteers (in collaboration with Sanofi)
- DNL758 (aka SAR443122; another RIPK1 inhibitor targeted at inflammation), currently recruiting participants for a Phase 2 study of lupus & in Phase 1 for COVID-19 lung disease (again in collaboration with Sanofi)
But of particular interest to us here at SoPD HQ were the slides on their LRRK2 inhibitor clinical trial data.
Founded in 2013 by a group of former Genentech executives, San Francisco-based Denali Therapeutics is a biotech company which is focused on developing novel therapies for people suffering from neurodegenerative diseases.
Ex-Genentechers. Source: Medicalstartups
Although they have product development programs for other condition (such as Amyotrophic Lateral Sclerosis and Alzheimer’s disease), Parkinson’s is definitely one of their primary indications of interest.
The company has been leading the charge in the development of LRRK2 inhibitors as a potential therapeutic class for Parkinson’s and they have recently made some big announcements.
What are LRRK2 inhibitors?