Methods of treating autophagy-associated disorders and related pharmaceutical compositions, diagnostics, screening techniques and kits

Abstract

The invention provides methods of treating autophagy mediated diseases and disorders and related pharmaceutical compositions, diagnostics, screening techniques and kits. In one embodiment, the invention provides a method of determining whether a subject suffers from, or is at risk of developing, and autophagy mediated disease state and/or condition by evaluating LC3 levels.

Description

RELATED APPLICATIONS[0001]This application is a continuation application of U.S. patent application Ser. No. 14 / 116,581, filed Nov. 8, 2013 of identical title which claims priority to International Patent Application No. PCT / US2012 / 037300 filed May 10, 2012, which itself claims priority from U.S. Provisional Application Ser. No. 61 / 484,653 filed May 10, 2011, entitled “Autophagy Diagnostics, Screening, and Therapeutics”, the complete disclosure of each of said applications is hereby incorporated by reference in its entirety.GOVERNMENT SUPPORT[0002]The invention described herein was funded in part by National Institute of Health Grant No. R01 A1069345. Accordingly, the United States has certain rights in the invention.FIELD OF THE INVENTION[0003]The invention provides methods of treating autophagy-associated disorders, and related pharmaceutical compositions, diagnostics, screening techniques and kits.BACKGROUND OF THE INVENTION[0004]Autophagy is a homeostatic process highly conserve...

AI Technical Summary

Benefits of technology

[0010]The elucidation of certain autophagic processes involved in the onset and progression of a variety of infectious and inflammatory-related disorders has led to the discovery of methods of treating and diagnosing such ailments. Further, the discovered novel methods have led to our being able to identify compounds that are effective as modulators of autophagy in the treatment of infectious and inflammatory-related disorders, as well as versatile techniques that enable the high through-put analyses of autophagic processes, including the disease state in a patient for diagnosis and / or monitoring therapy of the disease state. The present invention is directed to a method of identifying compounds which exhibit biological activity as modulators (inhibitors or agonists) of autophagy and consequently, can be used in the treatment of diseases which occur or are mediated through autophagy as a mechanism.

Problems solved by technology

When autophagy is deficient in the macrophages of infected mice, not only does this permit bacterial growth but also leads to an excessive proinflammatory response, with partial roots in sterile inflammation, leading to lung tissue destruction, necrosis and active tuberculosis.

We tested whether indications of such alterations may be detectable in animals not infected with M tuberculosis, since infection would complicate interpretations.

Nevertheless, not all aspects of IL-1 signaling are protective.

Whereas beneficial in control of extracellular bacteria, these features may not be desirable against M tuberculosis as discussed above and instead may contribute to immunopathology.

Images