Effects of age-dependent changes in cell size on endothelial cell growth
Inventors
Mammoto, Akiko • Mammoto, Tadamori
Assignees
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Publication Number
US-12433871-B2
Publication Date
2025-10-07
Expiration Date
Abstract
Described herein are angiogenic stimulating compositions comprising ML141 or a derivative thereof and methods of use of said angiogenic stimulating compositions for the treatment or prevention of a disease or injury in a subject, preferably a human subject of at least 50 years of age.
Core Innovation
The invention relates to angiogenesis-stimulating compositions and methods that use ML141 or a derivative thereof as the active agent. The methods stimulate angiogenesis in a subject in need thereof by administering a therapeutically effective amount of ML141 as a composition having an ML141 concentration of 0.1 μM to less than 15 μM.
A quantitative subject qualification is incorporated based on endothelial-cell characteristics measured from adipose tissue. The invention obtains an adipose tissue sample from the subject, stains the adipose tissue with a stain specific for endothelial cells, and measures the area of the stained endothelial cells.
ML141 is administered when the area of the endothelial cells is at least 1.5 times larger than the area of endothelial cells from a subject less than 50 years of age, to stimulate angiogenesis. The documented mechanistic context links age-dependent endothelial cell changes to CDC42–YAP1 signaling, where ML141-associated inhibition of CDC42 is described as restoring YAP1 nuclear translocation and decreasing senescence while improving angiogenesis-relevant blood vessel outcomes in gel implantation models.
Claims Coverage
Two independent claims are provided. Across these claims, the inventive features focus on ML141 concentration-defined compositions for stimulating angiogenesis and a decision criterion based on adipose-tissue endothelial-cell staining and endothelial-cell area relative to a <50-year-old reference group.
Concentration-defined ML141 angiogenesis stimulation
A method of stimulating angiogenesis in a subject in need thereof comprising administering a therapeutically effective amount of ML141, wherein angiogenesis in the subject is stimulated, and wherein the therapeutically effective amount of ML141 is administered as a composition having a ML141 concentration of 0.1 μM to less than 15 μM.
Adipose-sample endothelial-cell area qualification for ML141 administration
A method of stimulating angiogenesis in a subject comprising obtaining an adipose tissue sample from the subject; staining the adipose tissue with a stain specific for endothelial cells; measuring the area of the stained endothelial cells; and administering to the subject a therapeutically effective amount of ML141 when the area of the endothelial cells is at least 1.5 times larger than the area of endothelial cells from a subject less than 50 years of age, whereby angiogenesis is stimulated, wherein the therapeutically effective amount of ML141 is administered as a composition having a ML141 concentration of 0.1 μM to less than 15 μM.
The claim set covers stimulating angiogenesis using ML141 provided in a specified concentration range, and it further covers administering ML141 based on an adipose-tissue, stain-and-measure endothelial-cell area threshold relative to subjects less than 50 years of age.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
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