Study Rationale:
LRRK2 is a gene that plays a role in the development and progression of Parkinson's disease (PD). Mutations in the LRRK2 gene can increase the risk of developing PD and may contribute to its symptoms. NEULARK is a clinical trial testing the ability of the LRRK2 inhibitor NEU-411 to slow disease progression in individuals with PD who have genetic mutations in LRRK2 (LRRK2-RV) and a subgroup of individuals we predict to have increased LRRK2 kinase activity based on their genetic profile.
Hypothesis:
The prevalence of a LRRK2 mutation (LRRK2-RV) in PD is approximately 1-2 % of the overall PD population globally. However, in Israel the presence of LRRK2-RVs is increased to 10-20%. As such, we hypothesize that we will be able to identify a larger number of individuals with LRRK2 RV in Israel to contribute to the overall global NEULARK trial and allow for a sub-group analysis of the impact of NEU-411 on the progression of disease in LRRK2 RV.
Study Design:
This study will examine the impact of treatment with a LRRK2 inhibitor (NEU-411) for a 12-month period on the rate of PD progression. The primary endpoint will be the Roche digital device, similar to a smart phone, that can frequently monitor a variety of motor and non-motor symptoms associated with PD during the trial.
Impact on Diagnosis/Treatment of Parkinson’s Disease:
NEULARK is the first clinical trial in PD to identify individuals likely to respond to treatment with a companion diagnostic, and to use a primary digital endpoint. If successful we will be able to demonstrate the ability to identify the right patients for the right drug, and to provide a more sensitive measure to monitor disease progression in PD.
Next Steps for Development:
If the phase 2 trial NEULARK is successful, we intend to initiate Phase 3 registrational trial(s) with NEU-411 to seek approval of NEU-411 for the treatment of individuals with LRRK2-driven PD