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Use of the Lipid BMP as a Surrogate Marker for LRRK2 and GCase Activity

Study Rationale:
Mutations in LRRK2 and GBA1 are common genetic risk factors for Parkinson’s disease (PD) and offer promising targets for the development of PD therapies. Identification of a biologically relevant, surrogate marker that reflects disease-associated changes in these genes would facilitate the identification and testing of potential therapeutics. Recent studies indicate that a unique lipid called bis(monoacylglycerol)-phosphate (BMP) is elevated in individuals with LRRK2 mutations. These individuals also show reduced activity of Gcase, the lipid-metabolizing enzyme encoded by the GBA1 gene. This study will examine the use of BMP in biofluids as a marker for pathobiology in LRRK2 and GBA1-associated PD.

We hypothesize that disease-associated changes in LRRK2 and GCase activity will influence the production or extracellular secretion of BMP. 
Study Design:
Cells harboring mutations in LRRK2 and GBA1 will be treated with pharmacological agents that modulate the activity of these genes and their encoded proteins. We will then measure the effects that such treatments have on the production and release of BMP.

Impact on Diagnosis/Treatment of Parkinson’s Disease:
These studies will provide insights into the mechanisms by which mutations in LRRK2 and GBA1 cause disease.

Next Steps for Development:
The development of BMP as an easily measurable clinical biomarker will facilitate the monitoring of Parkinson's progression and the evaluation of potential therapies, now and in the future.


  • Kalpana M. Merchant, PhD

    Portland, OR United States

  • Albert L. Lu Lopez, MD, PhD

    Barcelona Spain

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