Sadis Matalon, Ph.D., Dr.Sc. (Hon.), FAPS, professor in the UAB Department of Anesthesiology and Perioperative Medicine, has received a new National Heart, Lung, and Blood Institute grant to advance the development of a promising therapy aimed at reducing severe lung injury caused by chlorine gas exposure.
The award's first phase, an R61 grant totaling $1.04 million, will support two years of research through July 2028. The project is being conducted in partnership with AntoXa, a biotechnology company with expertise in developing plant-based therapeutics for infectious diseases and chemical threats.
The research focuses on developing recombinant human hemopexin, a naturally occurring protein that binds and removes toxic free heme released during tissue injury. Antoxa will produce the protein in plants and Matalon and his team will evaluate its safety, effectiveness, and ability to prevent both acute and long-term lung damage following exposure to chlorine gas.
If the project successfully achieves its milestones during the R61 phase, the team will become eligible for the next stage of funding through an R33 award, which could provide up to $600,000 per year for additional preclinical studies and regulatory preparation before human testing.
Addressing a persistent public health threat
Matalon said the research was inspired by the continued threat chlorine gas poses to public health worldwide.
Global chlorine production reaches millions of tons annually, and the chemical is widely used in water treatment, sanitation, pharmaceutical manufacturing, and numerous industrial processes. While chlorine plays an important role in everyday life, accidental releases during transportation or industrial incidents can have devastating consequences.
“Exposure to chlorine represents a major threat to public health,” Matalon said.
Over the past several decades, accidental chlorine releases in cities around the world, as well as deliberate use of chlorine gas during acts of terrorism, have caused significant illness and death. People exposed to high concentrations of chlorine can develop acute respiratory distress syndrome, often requiring mechanical ventilation and intensive care. Survivors may face long-term complications, including pulmonary fibrosis and increased susceptibility to respiratory infections.
Even lower-level exposures can trigger serious respiratory symptoms, particularly among individuals with asthma and other lung conditions. Currently, treatment options remain largely supportive, with no approved targeted therapies available to directly counteract chlorine-induced lung injury.
Recognizing this unmet need, the NIH established the CounterACT Program to accelerate the development of medical countermeasures against chemical threats. Matalon has received continuous funding through the program since becoming the first UAB investigator awarded support through the initiative in 2006.
Advancing recombinant hemopexin
The research team will generate and evaluate recombinant plant-produced forms of human hemopexin designed to closely resemble the natural protein found in people. Investigators will assess how effectively the compounds bind heme, how long they remain in circulation, and whether they can reduce lung injury when administered after chlorine exposure.
Initial studies will be conducted in mice to evaluate the treatment's ability to reduce acute lung injury, prevent chronic respiratory damage, and improve survival. The team will also investigate how the therapy affects biological pathways involved in lung repair and inflammation.
Previous research conducted by Matalon's group has already demonstrated that earlier versions of recombinant hemopexin can remove toxic heme and promote lung recovery following chlorine exposure. The current project seeks to optimize the compound so that it remains active in the body for longer, thereby increasing its therapeutic potential.
If successful, the most promising candidate will advance to testing in rabbits during the R33 phase. Those studies will generate key data needed for discussions with the U.S. Food and Drug Administration regarding future human clinical trials.
Potential impact beyond chlorine exposure
Although the primary goal is to develop a treatment for chlorine-induced lung injury, Matalon said the implications could extend far beyond chemical exposure.
“We are proposing to synthesize and test the efficacy of recombinant hemopexin to decrease the onset and severity of lung injury and improve survival in a variety of hemolytic diseases,” Matalon said.
If ultimately translated into clinical practice, recombinant hemopexin could provide physicians with a novel tool for treating a range of severe pulmonary disorders while improving preparedness for industrial accidents and other chemical emergencies.
“I would like to thank the Center for Clinical and Translational Science, the UAB Department of Anesthesiology and Perioperative Medicine, and the Heersink School of Medicine for providing funds that enabled us to obtain the preliminary data necessary to compete for this highly prestigious and competitive award,” he said.