Unity Biotechnology, Inc.

Mayo Foundation for Medical Education and Research

Buck Institute for Research on Aging

Kythera Biopharmaceuticals, Inc.

Johns Hopkins University

Allergan Sales, Inc.

The Scripps Research Institute

Achaogen, Inc.

Buck Institute for Research Aging

Nathaniel E David

Remi-Martin Laberge

Robert M Moriarty

Judith Campisi

James L Kirkland

Tamar Tchkonia

Yi Zhu

Nadir Ahmeduddin Mahmood

Marco Demaria

Jan M A Van Deursen

Alain Philippe Vasserot

Darren J Baker

Bennett G Childs

Albert Davalos

Jennifer H Elisseeff

Chaekyu Kim

Okhee Jeon

Jamie Dananberg

Daniel Marquess

Pam Tsuruda

Jill Hopkins

Harry Sweigard

Yan Poon

John Gregory Reid

Achampeta Rathan Prasad

Serge P Lichtsteiner

Akhila Kumar Sahoo

Roy A Swaringen

Floyd E Romesberg

Roy A Swaringen, Jr

Ryan Cirz

Jan Ma Van Deursen

Jan MA Van Deursen

Claude Chapman

This invention establishes a new paradigm for treatment of Parkinson's disease (PD) by eliminating senescent cells that reside in or around the site of the disease pathophysiology. Exposure of test subjects to the herbicide paraquat (PQ) increases the risk for developing Parkinson's disease. The data in this disclosure show that PQ induces a senescence arrest and SASP in astrocytes, in culture and in vivo in mice, and senescent cell markers were present in astrocytes in midbrain tissue from PD patients. In a transgenic mouse model, senescent cell ablation protected against PQ-induced PD-like neuropathology. Removal of senescent cells from affected sites using small molecule agents that specifically target senescent cells can help prevent or ameliorate signs and symptoms of the disease.

Treatment of a senescence-associated ocular disease or disorder using a Bcl-xL selective inhibitor

Methods are provided herein for selectively killing senescent cells and for treating senescence-associated diseases and disorders by administering a senolytic agent. Senescence-associated diseases and disorders treatable by the methods using the senolytic agents described herein include cardiovascular diseases and disorders associated with or caused by arteriosclerosis, such as atherosclerosis; idiopathic pulmonary fibrosis; chronic obstructive pulmonary disease; osteoarthritis; senescence-associated ophthalmic diseases and disorders; and senescence-associated dermatological diseases and disorders.

Treating liver disease by selectively eliminating senescent cells

Treating cardiovascular disease by selectively eliminating senescent cells

This invention is based on the discovery that many eye conditions associated with aging are mediated at least in part by cells bearing a senescent phenotype. Senescent cells accumulate with age, and express factors that contribute to the pathophysiology of age related conditions. The data show that in age-matched patients, the severity of age-related conditions correlates with the abundance of senescent cells, and that clearing senescent cells can help abrogate the condition. Small molecule drugs that remove senescent cells from affected tissue in the eye are provided that have special efficacy in treating ophthalmic conditions. They not only inhibit progression of the disease, they can also reverse some of the pathophysiology—such as neovascularization and vaso-obliteration—that lead to vision loss. These senolytic agents have an appropriate dose and specificity profile to be effective in the clinical management of previously intractable ophthalmic conditions.

Methods of inhibiting pathological angiogenesis

Treating cognitive decline and other neurodegenerative conditions by selectively removing senescent cells from neurological tissue

Bile acids and related compositions and methods of synthesis and use. More specifically, deoxycholic acid and related compositions, said compositions being free of all moieties of animal origin and free of pyrogenic moieties.

Synthetic bile acid compositions and methods

This invention is based on the discovery that many eye conditions associated with aging are mediated at least in part by cells bearing a senescent phenotype. Senescent cells accumulate with age, and express factors that contribute to the pathophysiology of age related conditions. The data show that in age-matched patients, the severity of age-related conditions correlates with the abundance of senescent cells, and that clearing senescent cells can help abrogate the condition. Small molecule drugs that remove senescent cells from affected tissue in the eye are provided that have special efficacy in treating ophthalmic conditions. They not only inhibit progression of the disease, they can also reverse some of the pathophysiology&#x2014;such as neovascularization and vaso-obliteration&#x2014;that lead to vision loss. These senolytic agents have an appropriate dose and specificity profile to be effective in the clinical management of previously intractable ophthalmic conditions.

Technology to inhibit vascular changes that lead to vision loss in the eye

Polypeptides, viruses, methods and compositions provided herein are useful for the selective elimination of senescent cells. Method aspects include methods for inducing apoptosis in a senescent cell comprising administering to the cell a polynucleotide, virus, host cell, or pharmaceutical composition described herein. Other methods include expressing a pro-apoptotic gene in a senescent cell comprising administering to the cell the polynucleotide, virus, or pharmaceutical composition as described herein.

Composition comprising a gene vector that selectively depletes P16 positive senescent cells

Removing senescent cells from a mixed cell population or tissue using a phosphoinositide 3-kinase (PI3K) inhibitor

Compositions of matter for treatment of ophthalmic conditions by selectively removing senescent cells from the eye

Unit dose of an aryl sulfonamide that is effective for treating eye disease and averting potential vision loss

Growing community of inventors

Los Angeles, CA, United States of America

Nathaniel E David