A professor at the University of Veterinary Medicine has received money to improve the effectiveness of medicines against one of the most dangerous infectious diseases in the world.

David Russell, William Kaplan, Professor of Infectious Disease Biology in the Department of Microbiology and Immunology, has provided a $ 2 million grant over four years to the Mueller Health Foundation (MHF) to effectively develop new tuberculosis treatment regimens.

David Russell, Professor of Microbiology and Immunology (VETMI) at the University of Veterinary Medicine (CVM), is studying the study of tuberculosis drugs.

Although tuberculosis (TB) may be a disease of the past in some places, it is still one of the most deadly infectious diseases in the world today. According to the World Health Organization, only 1.4 million people died of tuberculosis in 2019 and now 1.8 billion people worldwide are infected with TB. In the United States, 13 million people have asymptomatic latent tuberculosis.

“It is worrying that the misuse of antibiotics has led to the emergence of tuberculosis strains that are partially or already completely resistant to the treatment options available today,” said Dr. Peter Mueller, president of the MHF. “Drug-resistant TB cases are on the rise, even in developed countries like the US, and require new treatment modalities.”

The grant comes in line with Russell’s article published in the Journal of Experimental Medicine on July 22, which established a new method to study how immune cells react to bacteria (Mtb) that cause tuberculosis.

“The translational nature of Russell’s work makes it a natural fit for the Mueller Health Foundation, an organization that supports solutions to find solutions to weaken infectious diseases around the world, especially anti-drug tuberculosis,” Mueller said. “At MHF we believe that integrating the host’s immune response into traditional antimicrobial research allows for paradigm shift, significantly improving tolerance for all ways to identify and develop newer, more effective, accessible and accessible treatment regimens. Tuberculosis.”

“We are pleased to see the value of the foundation in this work,” Russell said. “With their help, we will be able to bring our findings closer to potential life-saving therapies.”

The grant will help Russell and his team learn how different drugs cause bacteria that cause tuberculosis and how different populations of host immune cells can fight the infection.

“We hope that doing this analysis with drugs known in the first line and with new compounds in development will allow us to create a database of drug actions,” Russell said. “This database will allow rational medication regimens to be designed through computer simulation before working harder to perform in vivo tests and clinical trials.

“We know that anti-tuberculosis drugs are less active in vivo, and bacterial heterogeneity is a major driver of drug sensitivity and differential tolerance,” Russell said.

His approach addresses this problem: First, mice are infected with fluorescent Mtb, which shines to indicate their physical condition. These mice are treated with known drugs and their immune cells are analyzed using a single-cell profile to determine the relative sensitivity of intracellular bacterial populations to these drugs.

“The goal is to identify drug combinations that provide more effective coverage of the heterogeneous bacterial population,” Russell said. “We’ve started with well-known drugs, but we want to move that forward by introducing new metabolic inhibitor compounds that target bacteria in specific populations.”

In the first two years of the grant, Russell’s team plans to test four first tuberculosis drugs and several emerging drugs. “We anticipate that these data will reveal which Mtb populations are the most sensitive and which are the most sensitive to drugs,” Russell said. “It will also provide information on the relative kinetics of bacterial cleansing in an in vivo infection.” In parallel, the group will also investigate new compounds using this approach.

Once Russell’s team has established the effectiveness of each drug against different subpopulations of bacteria in vivo, they will be identified in combination with different defenses and sensitivities that may provide better coverage throughout the Mtb bacterial population.

“Along with these experiments, we will also investigate the molecule of epigenetic inhibitors that will help control immune cell infection or modulate the host cell environment and increase drug sensitivity to bacteria. we’re looking at it, ”Russell said.

In the final phase of the fellowship, Russell plans to design drug / drug combinations that provide better efficacy in the fight against Mtb in mouse models. If these experiments go well, the team would study drugs from human immune cells collected from patients with tuberculosis, which would pave the way for the development of human therapy.

“It’s very exciting to be able to deal with this disease from all sides,” Russell said. “The Mueller Health Foundation will allow us to move forward with a strategy that will create real solutions for patients in the distant future by optimizing combinatorial treatment with approved ready-made medications.”

Lauren Cahoon Roberts is Assistant Director of Communications at the University of Veterinary Medicine.