The FDA has granted approval to begin clinical trials of the AD-NP1 drug. It is a first-in-class drug for tissue regeneration, which targets cellular metabolism to promote tissue repair in multiple organs.
Analyzing heart tissue samples from mice and humans after a heart attack, UCLA cardiovascular scientist Arjun Deb detected high levels of the protein ENPP1. The researchers noted that this surge initiated a metabolic cascade that impaired energy production in various cell types within the damaged area, hindering recovery of the tissue. Notably, inhibiting ENPP1 activity enhanced repair of the heart and decreased formation of scar tissue, improving heart function.
Backed by funding from the National Institutes of Health, the Department of Defense, and the California Institute for Regenerative Medicine (CIRM), Deb’s group developed AD-NP1, a monoclonal antibody that inhibits ENPP1. Following successful safety and efficacy studies in mice and monkeys, the FDA has approved tissue repair drug AD-NP1 for human clinical trials.
Monoclonal antibodies, like AD-NP1, are laboratory-engineered drugs designed to mimic natural antibodies produced by the immune system. AD-NP1 selectively targets human ENPP1 without affecting other proteins. “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.
Disruptions in cellular energy pathways reduce cell performance. “That is what we saw: increased ENPP1 expression interfered with critical pathways that are needed for a cell to derive energy,” Deb said. In animal studies, AD-NP1 restored energy to heart muscle, improving contraction and preventing heart failure.
Because energy-generating pathways are conserved across cell types, Deb believes AD-NP1 could support repair in organs beyond the heart. His strategy enhances the body’s innate repair mechanisms without involving stem cells. “Rather, you use the power of the body’s own repair system and optimize it to make it so much better,” he said.
If human trials confirm animal results, AD-NP1 could inaugurate a new class of tissue repair drugs, potentially preventing organ decline after injury. “Cardiovascular disease is still the leading cause of death in the U.S. and around the world,” Deb noted. “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.”
