Methods and compositions for using alveolar macrophage phospholipase A2
Inventors
Shayman, James A. • Abe, Akira • Hiraoka, Miki
Assignees
US Department of Veterans Affairs • University of Michigan Ann Arbor
Publication Number
US-7319015-B2
Publication Date
2008-01-15
Expiration Date
2025-03-15
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Abstract
The present invention is directed to methods and compositions for improving pulmonary surfactant catabolism. More specifically, the specification describes methods and compositions for making and using a lysosomal phospholipase A2 in methods for the diagnosis, and treatment of disorders of phospholipid catabolism such as pulmonary alveolar proteinosis.
Core Innovation
The core innovation of the patent involves the identification and characterization of lysosomal phospholipase A2 (LPLA2) as a key enzyme responsible for degrading pulmonary surfactant phospholipids. The invention provides compositions and methods for using LPLA2 to enhance phospholipid catabolism. It also includes transgenic models with disrupted LPLA2 to study the disease phenotype, and highlights the enzyme's specificity, localization, and activity profile.
Claims Coverage
The patent claim focuses on increasing glycerophospholipid degradation in macrophage foam cells by contacting them with LPLA2 or active fragments, targeting lesions in arteries.
use of lysosomal phospholipase A2 protein for degradation of glycerophospholipids in macrophage foam cells
A method involving contacting macrophage foam cells with a lysosomal phospholipase A2 (LPLA2) protein, having the amino acid sequence of SEQ ID NO:2 or a fragment thereof, to boost glycerophospholipid breakdown.
targeting macrophage foam cells at arterial lesions
Specifying that foam cells are located at lesion sites within arterial walls, including in vitro and in vivo contexts, by administering LPLA2 compositions with suitable carriers.
The patent claims methods that involve using LPLA2 proteins or active fragments to enhance glycerophospholipid degradation in macrophages, especially targeting foam cells at arterial lesions, via pharmaceutical compositions.
Stated Advantages
LPLA2 is a major enzyme responsible for degrading pulmonary surfactant phospholipids, making it a target for treating surfactant-related disorders such as pulmonary alveolar proteinosis.
Using compositions with LPLA2 offers alternative therapies to invasive procedures, potentially reducing risks and improving patient outcomes.
Generation of transgenic mice lacking LPLA2 provides models to study phospholipidosis mechanisms and test therapies.
Understanding LPLA2's role in phospholipidosis explains the mechanism behind drug-induced phospholipid accumulation, guiding safer drug design.
Documented Applications
Treatment of surfactant metabolism disorders, including pulmonary alveolar proteinosis.
Screening for modulators of alveolar phospholipid catabolism.
Use of transgenic mice with disrupted LPLA2 gene as models for phospholipidosis and related lung diseases.
Treating atherosclerosis or related conditions by increasing LPLA2 activity in macrophage foam cells.
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