Welcome to the weekly TB R&D news highlights series! The goal of the WGND blog as highlighted during our launch is to stimulate global conversation pertaining to TB research and development. In order to further discussion, every Tuesday we will attempt to highlight selected stories in TB drug news — some revolutionary, some controversial, and some possibly bizarre. These posts may discuss past, current, or future events; our hope is that you will become an active participant in the discourse.
TB treatment for an Elephant Yields Benefits for Humans
Advances in TB treatment can come from some unexpected places. Several months ago, Action.org reported the successful treatment of Irene, a former circus elephant, and now a TB survivor. When Irene arrived to the Rio Grande Zoo, she underwent standard health examinations prior to being permitted to join the rest of the elephant herd. After months of examination, her trunk wash samples tested positive for TB, which had never before been successfully treated in a zoo elephant. The veterinarians took the unusual step of trying a multi-drug regimen that had been successful in humans. Irene received a two drug regimen of isoniazid and pyrazinamide, orally and rectally respectively every day for 1 year. After displaying typical adverse drug effects observed in human including as loss of appetite, weight loss, and bloating, Irene’s blood tests began displaying a decrease in anti-microbial antibodies suggesting the decline of the mycobacterium. So why is this news eventful ad relevant? What has it added scientifically? Quite a lot!
- Samples, protocols, and data gathered from Irene’s treatment were used to develop a standard, USDA approved blood test to identify Mycobacterium tuberculosis;
- rectal absorption of pyrazimamide was shown to be effective in achieving in vivo drug concentrations;
- and, if more elephants get sick…there’s an established protocol on hand.
BTZ043 active against different TB strains
A recent publication by Pasca et al. in Antimicrobial Agents and Chemotherapy (AAC) Accepts (epub ahead of print) presents recent results suggesting that BTZ043, a benzothiazionone pre-clinical candidate, holds promise against strains circulating in the clinic, not only the lab strains used in its discovery and early development phases. The target for this drug is heterodimeric deca prenylphosphoryl-β-D-ribose 2’-epimerase (encoded by the dprE1 and dprE2 genes). Spontaneous BTX-resistant laboratory TB strains harbor a mutation in DprE1 at Cys387, which is highly conserved in multiple actinobacteria. Therefore, the drug was tested on 240 individual Mtb isolates which included drug sensitive, resistant, MDR and XDR, isolated from 4 different clinical locations to determine whether resistance may already exist in the population. Results suggest, based on the limited sample size, sensitivity to BTZ by all strains exists. Furthermore, a yet to be developed diagnostic biomarker of Cys387 in the dprE1 gene could prove beneficial in monitoring resistance in future clinical trials of this drug.
What do you think of today’s news update? Do you have any TB News to share? Please feel free to add your news or reflect on ours by commenting below.