UCLA has received clearance from the U.S. Food and Drug Administration (FDA) to begin clinical trials for a new heart tissue regeneration drug, AD-NP1. The drug was developed by Arjun Deb, a UCLA professor of medicine and molecular, cell and developmental biology, along with his research team.
The research found that after a heart attack, levels of the protein ENPP1 increased in both mice and human heart tissue samples. This rise in ENPP1 disrupted cellular energy production and hindered tissue repair. Blocking ENPP1 improved heart healing and reduced scar tissue formation.
With support from the National Institutes of Health, the Department of Defense, and the California Institute for Regenerative Medicine (CIRM), Deb’s team created AD-NP1—a monoclonal antibody designed to inhibit ENPP1 activity. Tests in mice and monkeys showed promising results for both efficacy and safety.
Deb emphasized that the development was conducted entirely within UCLA using public funding: “This work has been entirely funded by taxpayer dollars, and done entirely within the University of California research ecosystem,” he said. “I have not taken a cent from any private donor or company to develop this drug. I hope this will form a model for future drug development at UCLA. This process has advantages of lower costs, potentially shorter development time and the principal investigator being in control of the science and having intellectual freedom with the development of the molecule, which is the most important of all.”
Monoclonal antibodies like AD-NP1 are engineered drugs that mimic natural immune system antibodies but are tailored to target specific proteins—in this case, human ENPP1.
“Much like people eat food to get energy, cells also require energy to multiply and grow and function, and this is more critical when the tissue is injured,” Deb explained.
He added that when animals were treated with AD-NP1 following injury, their hearts produced more energy: “That is what we saw: increased ENPP1 expression interfered with critical pathways that are needed for a cell to derive energy,” he said. “When AD-NP1 was used in animals, the heart muscle had more energy and contracted much more vigorously, preventing the development of heart failure.”
The team believes AD-NP1 could help other organs recover after acute injury because similar metabolic processes occur throughout different tissues.
Unlike some approaches to tissue regeneration involving stem cells, Deb’s method relies on enhancing natural repair mechanisms by modulating metabolism: “Rather you use the power of the body’s own repair system and optimize it to make it so much better,” he said.
If clinical trials confirm its effectiveness in humans as seen in animal studies, AD-NP1 may lead to a new class of drugs aimed at improving organ recovery after damage.
“Cardiovascular disease is still the leading cause of death in the U.S. and around the world,” said Deb. “All Americans want to lead healthier and longer disease-free lives. It’s a testament to the funding system we have in place in this country that within six or seven years, in an academic lab in a university setting, we have engineered a new drug that potentially could be helpful to many people with heart disease or other forms of organ injury.”
