Protein tyrosine kinase inhibitor (imatinib) used as a treatment to prevent multiple drug-resistant tuberculosis lethality and latent reactivation.
- Effective against drug resistant strains of tuberculosis.
- May be used in combination with current first-line treatments of TB.
Tuberculosis (TB) is a chronic infectious disease which primarily affects lungs and often co-infects individuals with HIV. Although curable, TB still continues to be a global health problem as one of the most common cause of death from an infectious disease. According to the World Health Organization, about one third of the world’s population is infected with latent TB and at risk for developing active disease, with higher prevalence in lower and middle income countries. Further, multidrug-resistant varieties of Tuberculosis (MDR-TB) pose an increasing threat to overall control of the epidemic by rendering majority of first line of drugs ineffective. Additional complexities of second line of drugs include adverse side effects, longer treatment period, and increased cost.
Mycobacterium tuberculosis post-infection survives in the human body by attacking and escaping the innate immune system. MDR-TB has the ability to use intracellular protein kinases for entry and survival in macrophages. Emory inventors have repurposed a protein tyrosine kinase inhibitor (imatinib), currently used in cancer therapy, for the treatment of MDR-TB. The inhibitor can be used alone or in combination with other antibiotics. The preclinical in vivo studies indicate that mice treated with imatinib alone, or in combination with an antibiotic, have reduced bacterial load in macrophages and granulomatous lesion in liver within 6 hours of administration. They have further shown imatinib to be effective against first line (rifampicin) resistant strains. In vivo data suggests that imatinib is efficacious alone and in combination with antibiotics to treat MDR-TB. This treatment may also have applications for patients diagnosed with HIV.
In vivo data available demonstrating the efficacy of treating MDR-TB with imatinib by itself and in combination with an antibiotic.
Publication: Napier, RJ et al. Cell Host Microbe. 2011; 10(5): 475 – 485