Lysosomal phospholipase A2 to study and treat bis(monoacylglycero)phosphate-related disorders

Unmet Need: A means to modulate endogenous bis(monoacylglycero)phosphate (BMP) levels

Bis(monoacylglycero)phosphate (BMP) is a lipid involved in many cellular processes such as endosomal and lysosomal trafficking. BMP dysregulation is implicated in a variety of neurodegenerative diseases and viral infections, but there are currently no therapeutics to modulate endogenous BMP levels, and little is known about its biosynthetic enzyme.

The Technology: BMP precursor enzyme for studying and treating BMP-related disorders

This technology identifies an enzyme, lysosomal phospholipase A2 (LPLA2), that is localized to late endosomes and lysosomes, involved with converting phosphatidylglycerol to lysophosphatidylglycerol, a precursor for the synthesis of BMP. LPLA2 has been shown to modulate BMP levels in human cell lines and to decrease cholesterol levels in fibroblasts of Niemann-Pick disease patients, a storage disorder in which cholesterol accumulates in lysosomes.

This technology has been validated with a cell model of Niemann-Pick disease type C.

Applications:

Therapeutic for disorders in which bis(monoacylglycero)phosphate (BMP) is dysregulated
Research tool for modulating and characterizing BMP-related disease pathways
Research tool for investigating cellular cholesterol levels

Advantages:

Aids understanding of BMP biology
Reveals a precursor in BMP synthesis
Treats disorders with BMP-dependent pathways
Treats Niemann-Pick disease type C

Lead Inventor:

Catherine Marquer, Ph.D.

Patent Information:

Patent Pending

Related Publications:

Chen J, Cazenave-Gassiot A, Xu Y, Piroli P, Hwang R Jr, DeFreitas L, Chan RB, Di Paolo G, Nandakumar R, Wenk MR, Marquer C. Lysosomal phospholipase A2 contributes to the biosynthesis of the atypical late endosome lipid bis(monoacylglycero)phosphate. Commun Biol. 2023 Feb 23;6(1):210.

Tech Ventures Reference:

IR CU23186
Licensing Contact: Sara Gusik