New drug proves effective against resistant and latent TB
drug-resistant forms of the disease as well as becoming the first
compound to treat the latent stage of this disease, which affects
nearly a third of the world's population, of which approximately 2
billion people are latently infected.
The latently infected represent an enormous reservoir for future outbreaks, as existing drugs are ineffective at targeting latent infection.
With the disease's fatality rate estimated at between 20 to 80 per cent, current estimates place the cost of treating a single case of MDR-TB at $250,000 (€209 000).
In the United States if a person fails to respond to all therapies and doctors cannot bring the active infection under control, that person must be quarantined indefinitely to prevent the spread of the drug-resistant infection in the population. In the most extreme cases, part of the lung may be surgically removed.
The compound (FAS20013) appears to be a potential new drug for treating all forms of tuberculosis and is directed specifically against slow growing mycobacteria that cause the disease rather than at a broad array of non-pathogenic organisms, which enhance the emergence of drug- resistant strains.
The team, from the Johns Hopkins Medical School, discovered no resistance had been encountered to FAS20013 in clinical isolates.
The short-term killing power of FAS20013 is greater than currently used drugs; for example, FAS20013 will kill more organisms in a 4-hour exposure than isoniazid or rifampin can during a 12- to 14-day exposure.
"The class of which this compound is the lead has a very different mechanism of action from any other drug currently used to treat tuberculosis. We have identified no cross-resistance with existing drugs. Every isolate we have tested so far has been susceptible to this compound," commented Nicole Parrish of Johns Hopkins Medical School, a lead researcher on the study.
The researchers are currently undertaking animal experiments that examine pharmacology and toxicology in preparation for an investigational new drug (IND) application to the Food and Drug Administration, which they hope to submit in a few months, so they may proceed to clinical trials.
If the drug lives up to the promise in human trials that it showed in the laboratory, it could be available for treatment of MDR-TB in two to three years, commented Albert Owens, President of FASgen, the company working to bring the drug to market.
TB is considered one of the greatest threats to health worldwide, with nearly 9 million new cases and 2 million deaths a year due to the disease.
The large numbers of people from all over the world who travel has exacerbated the spread of TB as has the worldwide rise of multi-drug resistance TB strains. The global spread of HIV with markedly increases susceptibility to tuberculosis has also worsened the situation.
The HIV pandemic has led to a resurgence of TB as a major public health problem. Immunodeficient HIV-positive patients are particularly vulnerable to TB, which is responsible for the deaths of at least 40 per cent of patients in this group.
The researchers report their results recently at the 2006 ASM Biodefense Research Meeting.
