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TB is a global killer. About 2 billion people or 1/3 of the global population is infected with Mycobacterium tubercolosis (Mtb). Annually, nearly 8 million infected people develop active TB, and 2 million die from the disease. Every year, 275 000 new cases occur in 11 countries in Southern Africa. |
Almost half of these occur in South Africa alone. Current therapy, using drugs from the 1960's, takes 6-9 months to complete, often leading to non-compliance (incomplete therapy).
This in turn leads to the emergence of resistant strains such as Multidrug-resistant TB (MDR-TB) and Extensively Drug-resistant TB (XDR-TB). The only solution is to develop a new generation of drugs which are administered reliably over a shorter period of time.
iThemba Pharmaceuticals in conjuction with Emory University in Atlanta, Georgia, USA, have targeted a glyoxalate shunt pathway which is unique to the TB bacterium, more specifically the Isocitrate lyase (ICL) enzyme.
The latent form of TB is a non-replicating, persistent state. This form exploits alternative sources of nutrients. Enzymes (such as ICL) required for the processing of the new nutrient pool are especially critical for the survival of the bacilli in this latent phase. iThemba Pharmaceuticals has recently generated encouraging data for a series of compounds which demonstrate Rifampin like activity.
PA-824, a drug candidate derived from a nitroimidazole core is showing very positive results in Phase II clinical trials.
Nitroimidazoles have been shown to kill replicating and non-replicating Mtb cells by a novel mechanism of action, namely the release of nitric oxide into cells. iThemba Pharmaceuticals in conjunction with the Innovation Fund in South Africa are synthesizing novel nitroimidazole derivatives.