Modulating the Latency of TB

UAB Research Foundation
posted on 10/31/2011

Tuberculosis (TB) is responsible for over two million deaths annually, or roughly one death every 18 seconds. Recently, the WHO has estimated that one third of the world’s population is infected with TB. The high incidence of this disease is related, at least in part, to its ability to remain latent for years in humans. Treatment of latent TB requires a six-to-nine month course of therapy, however, poor patient compliance and limited access to drugs in certain areas make treating this disease extremely difficult and has even spawned a new generation of drug resistant M. tuberculosis (Mtb). Researchers at the University of Alabama at Birmingham (UAB) have recently discovered proteins involved in regulating TB latency. These proteins can be therapeutically targeted thereby modulating latency and reactivation of TB thus creating favorable conditions for the treatment of this disease.

Suggested Uses

TB diagnostics and therapeutics

Advantages

An effective method for modulating the latency and reactivation state of TB
An assay to screen for and detect latent TB infections

Innovation Details

Detailed Description

The Dos two component system, composed of the sensor kinases DosS and DosT, is believed to regulate the transition into latent Mtb infection. Despite extensive studies, the host ligands of this system had not yet been established. Recently, UAB’s researchers have identified three crucial ligands of the Dos two component system. Hypoxia, NO, and CO have been identified as dormancy signals, where they bind DosS and DosT, generating the reduced and deoxygenated forms, respectively, and induce a state of bacterial persistence. This discovery has led to the development of methods suitable for modulating the activation status and detecting latent TB infection. The ability to therapeutically regulate the activation state of Mtb represents a major breakthrough in the clinical management of latent disease. This advancement will provide caregivers an opportunity to induce optimal treatment conditions thereby effectively reducing length of treatment and limiting emergence of drug resistant Mtb. In light of the difficulties in accurately diagnosing latent TB, UAB’s researchers have adapted this technology into a simple, reliable method for screening for latent Mtb infections. Overall, this technology addresses major limitations in the diagnosis and treatment of latent TB.

File Number: U2007-0039

Web site: http://www.uab.edu/uabrf

Disease: Infectious Diseases

Other Information:

MANAGING LICENSING ASSOCIATE

LEONA FITZMAURICE, PH.D.

fitzmaur@uab.edu (205) 934-7868

IP PROTECTION

U.S. Patent Application Serial No. 12/666,008, PCT filed June 20, 2008.

PRINCIPAL INVESTIGATOR

Andries Steyn, Ph.D., Department of Microbiology, UAB.

IP Protection