UCLA researchers have received clearance from the U.S. Food and Drug Administration to begin clinical trials for a new drug, AD-NP1, which is designed to promote heart tissue regeneration after injury. The development comes after years of laboratory research led by Arjun Deb, a professor at UCLA and member of the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research.
The team discovered that levels of a protein called ENPP1 increased in heart tissue following a heart attack, both in mice and humans. According to Deb, “increased ENPP1 expression interfered with critical pathways that are needed for a cell to derive energy.” By blocking this protein with the monoclonal antibody AD-NP1, the researchers observed improved heart repair and reduced scar tissue formation in animal studies.
Deb explained the approach: “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.” He added that 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 project was funded exclusively through grants from public agencies including the National Institutes of Health, Department of Defense, and California Institute for Regenerative Medicine. No private investors or companies were involved in developing AD-NP1. Deb emphasized this point: “This work has been entirely funded by taxpayer dollars, and done entirely within the University of California research ecosystem. 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 such as AD-NP1 are engineered to mimic natural immune system proteins but are designed to target specific molecules—in this case, human ENPP1.
Unlike some other approaches to tissue regeneration that use stem cells, Deb’s method focuses on enhancing metabolic pathways within cells to improve their ability to repair themselves. “Rather, you use the power of the body’s own repair system and optimize it to make it so much better,” he said.
Deb believes that if clinical trials confirm its effectiveness in humans as seen in animals, AD-NP1 could lead to new types of drugs aimed at improving recovery after organ injuries beyond just those affecting the heart.
“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.”
