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UTSW scientists receive Harrington Scholar-Innovator Awards

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(From left) Dr. Dawn M. Wetzel, Dr. Joachim Herz, Dr. V. Vinod Mootha

Three UT Southwestern physician-scientists hope awards from the Harrington Discovery Institute will further their research, eventually leading to new drugs for difficult-to-treat diseases. The faculty members are among 10 researchers nationwide selected for 2019 Harrington Scholar-Innovator Awards.

One of the recipients, Dr. Dawn M. Wetzel, is a pediatric infectious disease specialist who has been trying to develop a new drug for the deadly tropical disease leishmaniasis, which has made its way to the U.S. In the disease, caused by the parasite Leishmania, those infected develop skin ulcers or a disseminated disease that can lead to death. Dr. Wetzel, Assistant Professor of Pediatrics and Biochemistry, said millions of people worldwide are infected each year. Of those, thousands die, with 70 percent of those deaths in children.

“The drugs used to treat leishmaniasis don’t work very well, they are very toxic, and the parasites are developing resistance to them. This makes treating leishmaniasis very challenging,” Dr. Wetzel said. “In addition, the disease is spread by an insect called the sandfly, which has been spreading northward, and there have been cases of leishmaniasis diagnosed right here in Dallas.”

In her research, she has identified a small molecule that kills the parasite as effectively as clinically available drugs.

“These compounds work by affecting a protein called tubulin, which helps to make up a skeleton-like structure in parasites. The compounds lock this skeleton into place, which prevents the parasite from rearranging this skeleton when it needs to divide. Since the parasite can no longer divide, it dies,” Dr. Wetzel said.

With the support from the Institute, Dr. Wetzel’s goal is to develop a broad spectrum antiparasitic drug to treat a parasitic illness related to leishmaniasis called human African trypanosomiasis, otherwise known as sleeping sickness.

The Institute’s mission is to move scientific studies from the research phase to clinical trials. That makes the Harrington Award unique from other research programs that primarily provide assistance in the form of a grant.

“The recognition comes with a team of advisers with many years of experience in drug and biotech development who work with us and provide guidance on what would be the next step so that we can most efficiently move toward the commercialization of the product,” said Dr. Joachim Herz, Director of the Center for Translational Neurodegeneration Research at UT Southwestern, another Harrington Scholar this year.

Dr. Herz hopes the expert assistance will help his research lab develop a drug that prevents pain and tissue damage caused by excessive immune cell movement to surrounding tissues in a variety of inflammatory diseases.

Two years ago, researchers in his lab recognized that blocking the regulatory protein reelin could be the key to better therapy for these patients. Reelin works by regulating the stickiness of blood vessel walls, a mechanism that immune cells use to congregate at sites of inflammation. Consequently, blocking this signal dramatically reduces inflammation. During his investigations this was initially noticed as a benefit to treat multiple sclerosis and atherosclerosis. However, Dr. Herz is confident the discovery can be more widely applied to provide relief for other conditions.

“We found several ways to neutralize the reelin protein, which would then prevent the attachment step by which the immune cells adhere to the endothelial cell surface. That would be a nifty way to prevent the inflammation going on in autoimmune diseases such as Crohn’s disease, multiple sclerosis, and atherosclerosis,” said Dr. Herz, also Professor of Molecular Genetics, Neurology and Neurotherapeutics, and Neuroscience.

Dr. Herz wants to develop a humanized antibody to offset reelin in the blood to be used as a biologic for patients.

UT Southwestern’s third recognized Scholar, ophthalmologist-geneticist Dr. V. Vinod Mootha, wants to prevent his patients from having to undergo corneal transplantation surgery for a common genetic eye disease called Fuchs endothelial corneal dystrophy (FECD). Symptoms of the age-related disease range from blurred vision in moderate cases to swelling or scarring that can lead to blindness.

Dr. Mootha worked with researchers in the lab of Dr. David Corey, Professor of Pharmacology and Biochemistry, to identify small molecules called oligonucleotides that researchers hope can eventually be used to develop a topical medication to slow the progression of FECD. Dr. Mootha said these oligonucleotides work by targeting the toxic RNA that causes the disease.

“Our first aim is to continue to study these molecules and identify lead compounds that are both potent in our cell lines and our human corneal tissue model of Fuchs dystrophy and then we’d like to optimize their delivery,” said Dr. Mootha, Professor of Ophthalmology and in the Eugene McDermott Center for Human Growth and Development.

Currently, there is no other medical treatment for FECD. The most serious cases require surgery to prevent tissue damage.

“Fuchs dystrophy is the leading indication for corneal transplantation in this country. Approximately 15,000 to 20,000 are performed every year for this indication,” Dr. Mootha said.

According to the Harrington Discovery Institute, physician-scientists “whose research demonstrates innovation, creativity and the potential to impact standards of care in medicine” are selected as award recipients. In addition to research and drug development support, the award also provides monetary assistance that can reach up to a total of $700,000.

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