The combination of metformin and conventional tuberculosis drug as a new therapeutic strategy

 

Tuberculosis (TB) is a disease is a widespread infectious disease usually induced by mycobacteria called Mycobacterium tuberculosis (Mtb). Conventional pathogen-targeted TB therapy is effective, but problems with drug toxicity and resistance still exist in a long-term treatment. Singhal et al. demonstrated a diabetic drug, metformin (MET), mediates host cell responses to pathogen for promoting anti-Mtb activities. The article was published on Science Translational Medicine.

 

Researchers found MET controlled Mtb infection, reduced inflammatory effect, and strengthened the immune response to Mtb in mice. A decrease of disease severity is also observed in human after MET treatment. Compared with conventional TB drugs, this "host-targeted" therapy is less likely to generate microbial resistance. MET induces production of reactive oxygen species (ROS), which is a important factor in host cell antimicrobial response. Also, the autophagy process is mediated by adenosine monophosphate-activated protein kinase (AMPK). Further investigation on mice shows MET adjunctive therapy is effective in enhancing both first-line anti-TB drug INH and second-line anti-TB drug ETH in mice. There are some issues remain to be solved, such as confounders in the combination treatment, the exact dose of MET for TB patients, and the possibility that MET might affect prophylactic control of TB. Although all these issues require further clinical trials to test the safety and efficiency of MET in combination with other TB therapy, the combined regimens have shown promising positive clinical effects on TB patients.

 

Reference:
Sci Transl Med. 2014 Nov 19;6(263):263ra159.

Related Products

Cat.No.	Product Name	Information
S7306	Dorsomorphin 2HCl	Dorsomorphin 2HCl is a potent, reversible, selective AMPK inhibitor with Ki of 109 nM in cell-free assays, exhibiting no significant inhibition of several structurally related kinases including ZAPK, SYK, PKCθ, PKA, and JAK3. Also inhibits type Ⅰ BMP receptor activity. Dorsomorphin induces autophagy in cancer cell line.
S2697	A-769662	A-769662 is a potent, reversible AMPK activator with EC50 of 0.8 μM in cell-free assays, little effect on GPPase/FBPase activity.

Related Targets

AMPK