Progress Made Against Diarrheal Disease

Scientists develop new drug discovery method that validates investigational cryptosporidiosis drug.

Diarrheal disease results in more than 800,000 deaths around the world each year. Numerous studies have pointed to the unmet need for treatments against Cryptosporidium, which is a protozoan parasite that affects individuals through contaminated water.

Patients who are very young, elderly, or who have immune diseases are especially susceptible to diarrheal disease caused by the parasite, called cryptosporidiosis. The disease is a leading cause of death for children living in low-income countries.

In a new study published by Nature, investigators discovered and validated an experimental drug for the treatment of cryptosporidiosis. These findings are significant, since there are currently no vaccines or effective treatments.

"There's a lot of uncertainty when embarking on drug discovery for a notoriously intractable parasite such as Cryptosporidium, the cause of cryptosporidiosis," said Thierry Diagana, head of the Novartis Institute for Tropical Diseases. "Thanks to the commitment of our funding collaborators and urgent action of our academic colleagues, we've made an important step toward advancing a new treatment."

Currently, nitazoxanide is the only approved treatment for cryptosporidiosis; however, the drug has not been effective in treating infants and immune-compromised patients.

Developing novel treatments for the disease has proven challenging because the parasite perishes quickly in a laboratory setting and there is a lack of resources necessary to identify drug candidates, according to the authors.

In the study, the investigators developed a new drug discovery process that uses transgenic parasites and novel disease models.

Through screening compounds with anti-parasitic mechanisms, the authors discovered that pyrazolopyridines can inhibit Cryptosporidium. This process led to the identification and validation of KDU731, a Cryptosporidium PI(4)K inhibitor, according to the study.

In immunocompromised mice, the investigators found that treatment with KDU731 reduced the infection, according to the study. They also discovered that treatment resulted in resolution of diarrhea and dehydration in a model of neonatal calves, which closely resembles human disease.

Since there are no effective treatments for young children and immunocompromised individuals, these results suggest that KDU731 would effectively combat cryptosporidiosis.

The authors concluded that these results warrant further clinical studies of KDU731 for the treatment of cryptosporidiosis.