New drug prospect offers hope against hookworm infections

July 3, 2012, University of California, San Francisco

A drug candidate that is nearing clinical trials against a Latin American parasite is showing additional promise as a cure for hookworm, one of the most widespread and insidious parasites afflicting developing nations, according to a collaborative study at UCSF and Yale University.

The , known by the scientific name K11777, is under development at UCSF and is targeted to enter in the next one to two years to treat Chagas disease, a potentially fatal common to .

In the current study, researchers at the UCSF Center for Discovery and Innovation in Parasitic Diseases and the Yale University School of Medicine tested K11777 both in culture and in hamsters against the parasite Ancylostoma ceylanicum, one of several species of hookworm that afflict as many as 1.2 billion people worldwide.

The compound, which works by inhibiting cysteine proteases – key enzymes in the parasite's gut that help digest its blood meal – proved more than 90 percent effective in a single oral dose and completely cured hamsters of hookworm in two doses, according to a paper being published July 3, 2012 in the Public Library of Science (PLoS) Neglected Tropical Diseases.

The studies are the first step in assessing whether this class of drugs could be effective against hookworm in humans, either alone or in combination with current therapies, according to senior author Conor Caffrey, PhD, a senior scientist at the UCSF center and researcher in the UCSF Department of Pathology.

"The harbinger of concern is that for worm parasites of cattle and sheep, there is rampant resistance to the same or similar drugs that are currently being used to treat humans," Caffrey said. "Up to now, these have performed reasonably well but we're starting to hear reports of lower effectiveness, so we're working hard to identify new drug candidates before the inevitable happens."

Among parasitic diseases, hookworm infection is second only to malaria as a cause of disability worldwide. While not usually fatal, the infection is debilitating, slowing children's development and causing or exacerbating iron-deficiency anemia, which can be serious in young children and pregnant women, especially in those who already are undernourished.

Hookworm spreads when larvae from human waste penetrate human skin via moist soil, most commonly in underdeveloped areas where children go barefoot.

Among the surprises in the study was the potency of the compound against these worms. After starting with multiple doses, the team steadily cut back until they realized they had 90 percent effectiveness in one dose.

Because the current drugs, mebendazole and albendazole, are generally given as a single oral dose to treat the infection in humans, this level of potency was exactly what the researchers needed to consider it as a possibility for humans, Caffrey said.

If it proves safe and effective in humans, that single-dose therapy could be a potent new tool in the arsenal against hookworm and other worm parasites, providing a new solution that could be delivered using distribution systems already in place in under-developed conditions, according to the paper.

Even if K11777 does not end up as a new therapy, the discovery opens the door to developing cysteine protease inhibitors as a new class of drugs to treat and, perhaps, other intestinal nematode infections, Caffrey said. This also could have ramifications for treating similar in the animal health industry.

Explore further: Albendazole cuts enteric parasite prevalence in refugees

Related Stories

Albendazole cuts enteric parasite prevalence in refugees

April 19, 2012
(HealthDay) -- The administration of a single 600-mg dose of albendazole to United States-bound refugees prior to departure from Africa and Southeast Asia reduces the prevalence of intestinal nematodes, according to a study ...

Clinical trial of human hookworm vaccine begins at Children's National Medical Center

June 13, 2012
Today, the Sabin Vaccine Institute, in partnership with the George Washington University and the Children's National Medical Center, began vaccinating participants for a Phase 1 clinical trial of a novel human hookworm vaccine. ...

Availability and use of sanitation reduces by half the likelihood of parasitic worm infections

January 24, 2012
Access to sanitation facilities, such as latrines, reduces by half the risk of becoming infected by parasitic worms that are transmitted via soil (soil-transmitted helminths) according to a study published in this week's ...

Recommended for you

Creation of synthetic horsepox virus could lead to more effective smallpox vaccine

January 19, 2018
UAlberta researchers created a new synthetic virus that could lead to the development of a more effective vaccine against smallpox. The discovery demonstrates how techniques based on the use of synthetic DNA can be used to ...

Study ends debate over role of steroids in treating septic shock

January 19, 2018
The results from the largest ever study of septic shock could improve treatment for critically ill patients and save health systems worldwide hundreds of millions of dollars each year.

New approach could help curtail hospitalizations due to influenza infection

January 18, 2018
More than 700,000 Americans were hospitalized due to illnesses associated with the seasonal flu during the 2014-15 flu season, according to federal estimates. A radical new approach to vaccine development at UCLA may help ...

Zika virus damages placenta, which may explain malformed babies

January 18, 2018
Though the Zika virus is widely known for a recent outbreak that caused children to be born with microencephaly, or having a small head, and other malformations, scientists have struggled to explain how the virus affects ...

Certain flu virus mutations may compensate for fitness costs of other mutations

January 18, 2018
Seasonal flu viruses continually undergo mutations that help them evade the human immune system, but some of these mutations can reduce a virus's potency. According to new research published in PLOS Pathogens, certain mutations ...

Study reveals how MRSA infection compromises lymphatic function

January 17, 2018
Infections of the skin or other soft tissues with the hard-to-treat MRSA (methicillin-resistant Staphylococcus aureus) bacteria appear to permanently compromise the lymphatic system, which is crucial to immune system function. ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.