Grants Fund Drug Development for Devastating Tropical Diseases – Washington University School of Medicine in St. Louis

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Goal is better treatments for river blindness, intestinal worm infections

Victoria banas

Researchers at Washington University School of Medicine in St. Louis received two National Institutes of Health (NIH) grants totaling more than $ 5.5 million to develop new treatments for two types of devastating parasitic infections common in Africa sub-Saharan and Central and South Africa. America: river blindness and intestinal worm infections.

Both are classified as neglected tropical diseases by the World Health Organization (WHO). These diseases are concentrated among people living in poverty in tropical or subtropical climates, where resources to develop new treatments are often lacking.

One project will focus on onchocerciasis, a parasitic roundworm that causes blindness in rivers. Onchocerciasis infections are spread by black flies that thrive near fast-flowing rivers. About 270,000 people have gone blind and 1.2 million are visually impaired due to river blindness. Current drugs are limited in that they only prevent transmission of the parasite and cannot eliminate an established infection.

The second project will target a large group of infections caused by intestinal helminths, including hookworms, roundworms and whipworms. These helminths are soil borne and can cause malnutrition and anemia, especially in children and other vulnerable populations. Current therapies lose their effectiveness as these worms develop resistance to drugs that have long been used to treat and control parasites. According to the WHO, around 1.5 billion people worldwide are infected with STH.

Both drug development projects build on previous research conducted by Makedonka Mitreva, PhD, New Grants Co-Principal Investigator and Professor of Medicine and Genetics. Mitreva, who has conducted studies to understand the genetics and biology of these parasites, is working with co-principal investigator and medicinal chemist James W. Janetka, PhD, professor of biochemistry and molecular biophysics, to design new drugs at small molecules to fight these disabling infections.

“We are excited to be doing this kind of global health research, looking for new treatments for infections that tend to be overlooked in terms of research and funding for them, even as they affect millions of people. people, ”Mitreva said. . “We are taking advantage of all the genomic data that we have generated for these species of parasites over the past two decades to find new ways to target them with medical therapies. “

The collaborators also include a team that studies helminths transmitted by the ground. This team is led by Raffi Aroian, PhD, at the TH Chan School of Medicine, University of Massachusetts. Other collaborators, led by Sara Lustigman, PhD, head of the molecular parasitology laboratory at Lindsley F. Kimball Research Institute, the research arm of New York Blood Center Enterprises, are studying onchocerciasis.

The goal of the researchers is to attack elements of the parasite’s metabolism that are essential for the survival of the organism, with the aim of finding drugs capable of attacking more than one species of parasite at a time. For river blindness, they are mainly looking for new treatments that can kill adult parasites, as current therapies only target the larval stages of the parasite’s life cycle.

“We have identified potentially promising therapeutic targets that interfere with the way organisms process energy or perform other tasks necessary for survival,” Janetka said. “We are aiming for innovative targets which are relatively new treatment strategies, in particular for parasitic worms. It is possible that a drug we are developing can inhibit all worms. Panparasitic worm therapy would be wonderful, but there will also be the possibility of developing more than one drug, each one optimized for different species. “

Recent studies by Mitreva, Janetka and their colleagues have identified existing drug compounds, including some approved by the Food and Drug Administration (FDA) to treat other conditions, that show promise in their potential to treat these parasitic infections. A number of these drugs inhibit what researchers call bottleneck enzymes, or proteins that are essential for the body to survive. When the enzymes in the bottleneck are blocked or removed, the parasite dies, making these drugs interesting possibilities for new therapies. Such FDA-approved drugs could also be used as a starting point to design even more specific and targeted therapies for these parasites to ensure that all possible side effects are minimized.

“The fact that many of these drug candidates are already approved by the FDA could dramatically speed up the drug development process,” Janetka said.

Mitreva added: “The World Health Organization aims to eliminate blindness from rivers by 2030, and we believe that developing effective treatments against adult worms – and not just to target the spread of the disease. infection – will be necessary to achieve this. We have promising drug targets and look forward to developing new treatments for these debilitating infections that impact so many lives around the world. “

This work is supported by the National Institutes of Health (NIH), grant numbers R01EY033195 and R01AI159450.

The 1,700 physicians at the Washington University School of Medicine are also on the medical staff at Barnes-Jewish and St. Louis Children’s Hospitals. The School of Medicine is a leader in medical research, education, and patient care, and is a major recipient of research funding from the National Institutes of Health (NIH). Through its affiliations with Barnes-Jewish and St. Louis Children’s Hospitals, the School of Medicine is linked with BJC HealthCare.


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