University Given $3.9M to Advance Potential COPD Therapy to Clinical Testing

Researchers at Washington University School of Medicine in St. Louis have been awarded $3.9 million in funding to continue developing a treatment candidate that reduces mucus production and inflammation in debilitating lung diseases, such as chronic obstructive pulmonary disease (COPD) and asthma.

The award from the Department of Defense (DoD) will support preclinical studies in human cells and animal models to determine safety, and optimal doses for patient studies, and the effectiveness of this MAPK inhibitor.

Led by Michael J. Holtzman, MD, a professor of medicine and director of the university’s Division of Pulmonary & Critical Care Medicine,  the research aims to gather data to support future clinical trials to evaluate this treatment candidate.

“Obstructive lung diseases, such as asthma and COPD, are the third leading cause of death due to disease in the United States. But we have no effective treatments that address the root causes of these illnesses or halt disease progression. We can only try to relieve symptoms,” Holtzman said in a university press release.

“This grant will allow us to continue research into a new drug candidate that our group developed and that has shown evidence of stopping and correcting what goes wrong in the lungs when this type of disease process is triggered,” Holtzman added.

COPD, a chronic lung disease, is characterized by features such as inflammation and overproduction of mucus. This is normally triggered by insults to the lungs, such as viral infections, smoking, or air pollution.

In normal circumstances, stem cells in the lungs help repair the damage caused by these insults, originating new cells that line the lungs’ airways. After the repair process is finished, stem cells return to a dormant state, participating in the renewing and repairing of lung tissue only when needed.

But in some people, these stem cells can remain activated long after the injury or infection is resolved. “This leads to overproduction of mucus and excessive inflammation that can interfere with lung function with airway obstruction and difficulty breathing,” Holtzman said.

In his research, Holtzman and his team discovered that this excessive inflammation and mucus production are dependent on the mitogen-activated protein kinase (MAPK) signaling pathway.

Since no MAPK inhibitors were available, the team developed a treatment candidate designed to bind and block two molecules from this pathway. Studies in cells and animal models demonstrated that the therapeutic candidate could not only reduce inflammation and the consequent mucus production, but also return the stem cells to their normal state of activation.

The grant will support additional preclinical studies evaluating whether the candidate is safe and promising enough to enter clinical studies. The safety work will be conducted by NuPeak Therapeutics, a biotechnology company founded by Holtzman to advance the development of the treatment candidate.

In addition to asthma and COPD, Holtzman and colleagues are investigating whether this potential treatment may also be useful with severe COVID-19 infections.