Study Rationale:
The LRRK2 protein is overactive in people with Parkinson’s and a mutation in the LRRK2 gene. Recent research shows LRRK2 may be overactive in a sporadic (cause unknown) Parkinson’s population as well. Drugs are being developed to block the function of LRRK2 to treat the disease.
Hypothesis:
We hypothesize that a drug that binds to one part of the LRRK2 protein can block its role in causing Parkinson’s disease.
Study Design:
Drugs bind to proteins like keys fit into locks. We are going to try about 2000 molecules (keys) to see if we can get a starting “fit” into LRRK2 (the lock). The best way to improve on the first key we find is to take a picture of the key in the lock, which we can do with x-rays. Then, based on where we see the key may need to be slightly bigger or slightly smaller, we will use chemistry to make very small changes in the key until we get the right fit.
Impact on Diagnosis/Treatment of Parkinson’s Disease:
Our project may eventually lead to a new therapy for people with Parkinson’s and a LRRK2 mutation and potentially a broader disease population.
Next Steps for Development:
If we are successful, our work will spawn a full drug discovery effort where our lead molecule(s) will be tested in models and further chemical modifications to allow the drugs to access the brain will be pursued.