Objective/Rationale:
There is great excitement that drugs targeting an enzyme called LRRK2 may have utility in the treatment of Parkinson’s disease. Some companies are attempting to develop LRRK2 inhibitor drugs. In addition, there is another enzyme very similar to LRRK2 called LRRK1, and it is likely that LRRK2 inhibitors being developed will also inhibit LRRK1. Little is known about what LRRK1 does or what the consequences of inhibiting LRRK1 will be. This proposal will generate reagents called monoclonal antibodies that should help the research community understand LRRK1 function. This will help to define whether LRRK2 inhibitors that target LRRK1 will have unwanted side effects.
Project Description:
This project involves working closely with MJFF and two companies (Epitomics and Neuromab) to raise state of the art antibodies that detect LRRK1 but not the related LRRK2 enzyme. Our laboratory will provide Epitomics and Neuromab with the key LRRK1 antigen to raise the antibodies against. Our lab will then evaluate the quality of the antibodies that are raised in various applications (immunoblot, immunoprecipitation and immunohistochemistry). We will select the optimal antibodies for each application and ensure that these are distributed with no strings attached to the scientific community working on LRRK1/LRRK2 and Parkinson’s disease.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
We hope that the LRRK1 antibodies will be useful to researchers as well as pharmaceutical companies who are studying LRRK1 and LRRK2 and evaluating the utility of LRRK2 inhibitors for the treatment of Parkinson’s disease. We anticipate that this research will contribute to helping pre-clinical evaluation of LRRK2 inhibitors. Understanding the roles of LRRK1 is vital to the pharmaceutical companies developing LRRK2 inhibitors. Overall this could aid and speed up the development of a new treatment for Parkinson’s disease.
Anticipated Outcome:
We aim to produce state of the art antibody reagents that will help with the characterization and understanding of LRRK1. These reagents will greatly facilitate the ability of researchers and pharmaceutical companies to better understand LRRK1 and LRRK2 biology and the physiological effects that drugs that target these enzymes will have.