Thuggacines for the treatment of tuberculosis

Reference Number TO 02-00214

Challenge
According to the World Health Organisation (WHO) one-third of the world's population is currently infected with the tuberculosis (TB) bacillus. Each year about 1.7 million people die from tuberculosis (TB) and every second a person in the world gets newly infected with TB bacilli. However, people infected with TB bacilli will not necessarily fall ill of the disease. The immune system "walls off" the TB bacilli which, protected by a thick waxy coat, can stay dormant for years. But when someone's immune system is weakened, the risk to be taken sick is higher (e. g. people infected with HIV are much more likely to develop TB).

Until 50 years ago, there were no medicines to cure TB. Now, strains resistant to a single drug are documented; but even worse, strains resistant to all major anti-TB drugs show an upward trend. A particularly dangerous form of TB is the so-called multidrug-resistant TB (MDR-TB), which is caused by TB bacilli resistant to at least isoniazid and rifampicin, the two most powerful anti-TB drugs. Rates of MDR-TB are drasticly increasing. In conclusion, there is an urgent demand for new alternative antibiotics to combat the tuberculosis pathogens.

Technology
Thuggacines are novel macrocyclic lactones isolated from different Myxobacteria belonging to the genera Sorangium and Chondromyces. The compounds show strong antibacterial properties especially against nocardia and mycobacteria including M. tuberculosis. Furthermore, Thuggacines show low cytotoxicity and can be easily produced via fermentation at reasonable costs. The multiple glycosylated macrocycles are promising lead structures for drug development.

Commercial Opportunity
New alternative antibiotics like Thuggacines are urgently needed to cope with the re-increasing number of tuberculosis infections worldwide. Offered are

- A license covering etnangien, stabilised derivatives and the
respective genecluster for therapeutic development
- Co-operation for further development.

Developmental Status
So far in vitro cell culture data are available.

Patent Situation
German patent granted (DE 19542786), European patent application filed 2006 (EP06125361.3), PCT application pending (PCT/EP2007/062107).

Further Reading
Steinmetz et al. 2007. Chem. Eur. J. 13, 5822 – 5832.