In the Sept 21, 2007 issue of Science, researchers have published the genome sequence of a major parasite: the worm brugia malayi. B. malayi causes elephantiasis, one of the 13 "neglected tropical diseases" that collectively affect close to 3 billion people in the developing world. (See BioWorld Today, Dec. 28, 2006, and Dec. 29, 2006.)

Filarial parasites, or threadlike worms, affect more than 150 million people. Though the diseases they cause are not usually fatal, they are debilitating to the point of trapping their victims in poverty. B. malayi has proven especially recalcitrant because the adult worms can survive for up to eight years in their human hosts, and current treatments kill larvae but not adults.

One reason for its longevity is that b. malayi seems to have a better invisibility cloak than even Harry Potter. Many people who are infected with b. malayi show no symptoms. "Although the immune system probably is aware that the worm is there, it doesn't mount an immune response," Elodie Ghedin, assistant professor of infectious diseases at the University of Pittsburgh School of Medicine and first author of the Science paper, explained to BioWorld Today.

The researchers, who sequenced the worm's genome and compared it to that of a free-living worm, found several genes that may help b. malayi evade the immune response of infected individuals. Besides being potential targets in elephantiasis treatment, such genes also might be able to guide transplant medicine. With a constant shortage of organs for transplantation, surgeons have been looking to other species as possible providers from everything from kidneys to insulin-producing cells. If scientists can figure out just how b. malayi avoids triggering an immune response, they might be able to teach baboon hearts or pig islet cells the same trick.

In fact, that crossover with transplant medicine might be the best hope of elephantiasis sufferers for ultimately getting therapeutic benefits from the findings. Developing treatments for neglected tropical diseases faces unique economic challenges because those who need them usually do not constitute a "market" in the sense of having money to spend on drugs. In fact, most of those affected by neglected tropical diseases live on less than $2 a day.

So while a unique target is much sought after, for example, in cancer drug development, to some extent the opposite is true for neglected tropical diseases. Eric Sorkin, chairman and CEO of Immtech Pharmaceuticals Inc., said the key to success for for-profit companies in that area lies in doubling up on indications.

"If the only indication for a new compound were [a neglected tropical disease], it would be very difficult for any company, including us, to move forward with it," Sorkin told BioWorld Today.

Immtech is developing its lead compound pafuramidine (DB829) for African sleeping sickness, and announced last week that it has been granted orphan drug status by the FDA. But the company also is developing pafuramidine in two other indications: pneumocystis carinii pneumonia (PCP) and malaria.

All three indications are orphan drug indications in the U.S., but PCP and malaria have viable markets. Pneumocystis pneumonia, which was one of the harbingers of the AIDS epidemic in the early 1980s, is a complication in immunocompromised individuals. While it is rarely seen in Western AIDS patients these days due to the success of antiretroviral treatment, there is a U.S. market for cancer and transplant patients. And malaria, like HIV and tuberculosis, primarily affects the poor of the developing world, but is nevertheless a Western priority. (See BioWorld Today, Dec. 28, 2006.)

Sorkin said that the multiple indications enable the pursuit of an economies of scale that make the drug cheaper to manufacture per dose for the combined needs of the three indications.

Additionally, the clinical trials for sleeping sickness also provide the company with safety data for its other indications. "Every single patient that takes your drug is part of your safety profile," Sorkin said. This is particularly true for sleeping sickness and pneumocystis pneumonia, which have very similar dosing regimens, but there also is carryover with the malaria trials.

Overall, Sorkin said, such synergies benefit both sides of the equation: "It's been very effective in keeping our costs down both for shareholders and for NGOs."

Ghedin acknowledged that "in this case, we don't have a clear path" toward turning the basic findings into therapeutics, but she also is optimistic about the chances of getting drugs based on her findings to those who need them. She noted that even if there is no commercial interest, nonprofits like Sabin Vaccine Institute and public-private partnerships recently have made progress against a number of neglected tropical diseases.

And, she said, for elephantiasis at least, the work answers those who say developing drugs against neglected tropical disease is difficult because there is no basic science research on the most promising targets: "Well, here you go."