Objective/Rationale:
LRRK2 (Leucine-Rich Repeat Kinase 2) is a protein thought to be involved in regulating signaling pathways in cells. Mutations in the gene for LRRK2 are associated with some familial forms of Parkinson’s disease (PD). Ultimately, a better understanding of the biological role of this protein may provide information about cellular pathways triggered in non-familial forms of PD pathogenesis as well.
Antibodies, molecules normally used by our immune system to recognize foreign substances, are also used by research scientists to study proteins. Antibodies can be made that recognize any protein of interest and then used to determine, for example, where that protein resides in the body or how its levels change in disease. In 2010, MJFF generated LRRK2-specific antibodies that were characterized by a number of PD researchers. MJFF will work with a contract research organization to develop a test to detect LRRK2 that utilizes these antibodies, along with others that have been well-characterized.
Having the ability to precisely measure levels of LRRK2 protein in a variety of biological samples may provide researchers with a novel biological marker of PD progression. Moreover, this will enable scientists to correlate genetic differences in LRRK2 to quantitative differences in LRRK2 levels, perhaps lending further insight to the role of LRRK2 in PD pathogenesis.
Project Description:
MJFF will acquire reagents for the development of this assay from Invitrogen (www.invitrogen.com), Neuromab (www.neuromab.org) and Epitomics, Inc. (www.epitomics.com – Epitomics generated the original MJFF-supported LRRK2 antibodies). Working with Covance (www.covance.com), these reagents will be used to develop a sensitive test that can detect LRRK2 protein in a number of biological samples. Upon generation, MJFF will ensure that this assay is then made widely available to the PD research community.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
A major obstacle in scientific progress is access to essential research tools. In developing a reliable method to quantitate levels of LRRK2 protein, and making such a tool widely available to investigators in academia and industry, MJFF strives to accelerate LRRK2 research and therapeutic development.
Anticipated Outcome:
This project will result in an assay to quantify LRRK2 protein levels for use by the PD research community.