TB Alliance: Putting science to work for a faster TB cure

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TB Alliance Announces Four Drug Discovery Collaborations

Early-Stage Research Partnerships Aim to Stock Tuberculosis Drug Pipeline

The Global Alliance for TB Drug Development (TB Alliance), a not-for-profit product development partnership accelerating the discovery and development of new drugs to fight tuberculosis (TB), announced at the Global Health Council Conference today that four drug discovery collaboration agreements have been signed. All four projects have the potential to generate compounds active against drug-resistant tuberculosis and show promise to advance the science of TB drug development.

"These partnerships show that the TB Alliance is  aggressively increasing the depth and strength of its portfolio to ensure that promising new TB drug candidates continue moving toward the clinic," said Dr. Mel Spigelman, CEO of the TB Alliance. "Tuberculosis is responsible for the death of one person approximately every 20 seconds - and there is a significant need for novel medications to combat growing bacterial resistance to current drugs and to reduce the duration and complexity of therapy."

These recent discovery partnerships include programs with:

 

  • Anacor Pharmaceuticals, a biopharmaceutical company developing small-molecule therapeutics derived from its boron chemistry platform, to explore a novel anti-bacterial drug target for use in tuberculosis therapy. Under the agreement, Anacor will provide the TB Alliance with a non-exclusive, royalty-free worldwide license for any compounds ultimately registered for a TB indication. Compounds that attack novel targets have the potential to be effective against drug-resistant disease.

 

  • Colorado State University to test whether inhibition of menaquinone biosynthesis - a key component of the energy generation system in M. tuberculosis (M.tb) - has the potential to eradicate the disease in vivo. The compounds, first developed as cholesterol synthesis inhibitors, will be "retro-designed" via cycles of synthetic medicinal chemistry and evaluated as inhibitors of menaquinone biosynthesis and bacterial growth. The most promising compounds will be employed in an animal model of TB, and a more advanced discovery program could be developed if the studies are successful. Inhibition of menaquinone biosynthesis is a novel approach and therefore compounds that inhibit this process have the potential to be effective against drug-resistant disease.

 

  • Institute of Microbiology (IMCAS), a member institute of the Chinese Academy of Sciences, to discover and develop novel anti-TB agents from natural sources, including microbial metabolites and traditional Chinese medicines. IMCAS will test 24 natural product extracts with potential anti-tubercular activity and will collaborate to further test these extracts, purify and identify the active components, and develop those that prove most promising. The deficiency in natural product screening directly against M.tb combined with China's strong track record of successfully developing new drugs from traditional Chinese medicines, suggest that such screenings may yield novel active compounds, which would have the potential to be effective against drug-resistant disease. 

 

  • New York Medical College to explore the type 1 topoisomerase (Topo 1) enzyme that facilitates the unwinding of DNA, which is required during normal cell processes. (The type II topoisomerase DNA gyrase is already a proven target for anti-tuberculosis therapy.) The goals of the Topo I program are to determine, using genetic techniques, whether inhibiting Topo I would kill tuberculosis bacteria, as for DNA gyrase, and to develop a method to identify Topo I inhibitors. Since bacterial Topo I is a new drug target, inhibitors that kill tuberculosis bacteria have potential for use against both drug sensitive and drug-resistant tuberculosis.

 

Every year, nearly 9 million people worldwide fall ill with TB and nearly 1.8 million people died from the disease in 2007 alone. It is estimated that the bacillus that causes TB infects one-third of the world's population and the threat of drug-resistance is growing at an alarming rate. TB hits the some of the world's most vulnerable populations and devastates whole families, villages and even whole nations. New, faster-acting, simpler drug regimens are critical to defeating this ancient disease. The TB Alliance is leading this global effort, discovering and developing new compounds and acting as a catalyst to encourage information sharing and coordinated efforts among all organizations involved in finding new treatments.