Treating atherosclerosis by removing senescent foam cell macrophages from atherosclerotic plaques

US10328058B2 · kind B2 · utility

Assignees

• Mayo Foundation for Medical Education and Research · US
• Unity Biotechnology, Inc. · US
• BUCK INSTITUTE FOR RESEARCH ON AGING · US

Inventors

• Darren J. Baker · Rochester, US
• Marco Demaria · Groningen, NL
• Albert Davalos · San Rafael, US
• Bennett G. Childs · Rochester, US
• Jan M.A. van Deursen · Rochester, US
• James L. Kirkland · Rochester, US
• Tamar Tchkonia · Rochester, US
• Yi Zhu · Chengdu, CN
• Nathaniel David · Brisbane, US
• Remi-Martin Laberge · San Francisco, US
• Judith Campisi · Berkeley, US

Key dates

• Filing date: Oct 24, 2017
• Grant date: Jun 25, 2019
• Expiry date: Oct 24, 2037

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C12N2501/999
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

Foamy macrophages with senescence markers accumulate in the subendothelial space at the onset of atherosclerosis where they drive pathology by increasing expression of key atherogenic and inflammatory cytokines and chemokines. In advanced lesions, senescent cells promote features of plaque instability, including elastic fiber degradation and fibrous cap thinning, by heightening metalloprotease production. This invention provides methods and materials for treating arthritis by removing senescent cells in or around atherosclerotic plaques, thereby stabilizing the plaques, inhibiting rupture of the plaques and pathological sequelae that manifest as coronary artery disease.