The protozoan parasite itself that causes the disease, Trypanosoma cruzi, infects upto 18 million people each year. Until now, there has been no effective treatment for the long-term, chronic form of Chagas disease, which kills up to one-third of those infected, usually by heart failure.
Currently used treatments, nifurtimox and benznidazole, can be used for the early chronic phase. However there are drawbacks. Benznidazole often has toxic side effects and does not work once the disease has entered the chronic phase.
Two researchers from the Howard Hughes Medical Institute (HHMI) found that in mice, TAK-187, prevents T.cruzi from producing a member of the steroid family called ergosterol, which is essential to the parasite's life cycle.
The compound is currently in development as a systemic antifungal agent, but the results of the current study suggest that drugs of this type, would be more effective for Chagas. According to Julio Urbina from the Venezuelan Institute for Scientific Research and Miguel Angel Basombrio from the National University of Salta, the finding could be a "superior alternative to currently available therapy in the management of chronic Chagas disease."
Takeda Chemical Company, the largest pharmaceutical manufacturer in Japan, has patented TAK-187 as a systemic antifungal agent. "The clinical development of this compound as an anti-T-cruzi agent in humans will depend on legal and economic agreements with Takeda, which are being sought through the World Health Organisation," said Urbina.
The scientists infected a group of mice with T.cruzi, and then treated those mice with TAK-187, benznidazole, or nothing at all. While both drugs eliminated T.cruzi from the blood of infected animals, the researchers found that TAK-187 was more effective at preventing cardiac and skeletal inflammation and tissue damage, with no toxic side effects. Cardiac and skeletal damage occur in chronic Chagas infection, causing crippling and death.
More significantly, TAK-187 was effective at a dose that was both 10 times lower and administered less frequently than that of benznidazole. The researchers think this may be because the new compound is eliminated more slowly than benznidazole from the treated animals and is also more resistant to metabolism by the mammalian host.
Urbina, Basombrio and colleagues report their discovery in an early online publication of the April issue of the journal Antimicrobial Agents and Chemotherapy and its findings seem to back up an earlier study carried out in 2003 also by Urbina and colleagues. Published in the International Journal of Antimicrobial Agents, they also found TAK-187 effective against drug-resistant strains of T.cruzi.
These results, together with the previous publication bring hope to the thousands that suffer from the disease and the results strongly support the view that a more efficient treatment for Chagas disease could be available.
Urbina and colleagues now plan clinical trials to determine the safety and efficacy of TAK-187 in patients with Chagas disease.
"We must now examine the safety and effectiveness of therapeutic doses of this drug and determine the optimal administration schedule, the treatment duration, and its possible combination with other drugs," said Basombrio.
"Only one per cent of the new drugs introduced to the market in the last 25 years were developed to treat tropical diseases, despite the enormous unmet need for such compounds," Urbina added.
"Only 10 per cent of current global health research is directed to address the medical needs of 90 per cent of the human population."