Researchers have discovered that a drug previously developed at UCLA to help heart tissue repair itself after a heart attack may also help repair and regenerate kidney tissue.
The drug, called AD-NP1, was recently approved by the FDA for Phase 1 clinical trials in humans and works on heart tissue by blocking proteins that interfere with healing and prevent the internal organs from fully recovering. Researchers now find that blocking this protein in kidney tissue accelerates repair after kidney injury in mice.
The new discovery is cell stem cellsbased on years of research in UCLA cardiovascular scientist Arjun Deb’s lab.
His group found that injured kidneys produce a protein called ENPP1, which starts a metabolic chain that disrupts energy production and function of multiple cells in the injured area, impeding tissue repair. Researchers found that blocking ENPP1 enhanced kidney repair and reduced scar tissue formation, thereby improving kidney function. Deb’s group previously confirmed that blocking ENPP1 in heart tissue improves healing.
Deb’s team examined kidney biopsies from patients with chronic kidney disease and found that ENPP1 was expressed at higher levels than in healthy tissue. They then fed the mice a diet that was harmful to their kidneys, and administered a drug that causes kidney damage to both normal mice and mice that had the gene that produces ENPP1 knocked out. Blood tests showed that these mice all showed significant increases in serum creatinine, BUN, and cystatin C, signs of renal dysfunction. However, after four weeks, these levels were significantly reduced in mice unable to produce ENPP1 compared to control mice, indicating that their kidneys were healing.
After confirming that blocking the metabolic cascade triggered by ENPP1 improved kidney repair, the researchers induced kidney damage in normal mice and administered their drug, AD-NP1. After just seven days, the mice showed improved kidney function, and subsequent kidney tests showed less scarring.
These animals had much better results. Their kidneys were less damaged and their kidney cells were growing more. We found that the same mechanism observed in the heart also applies to the kidney. After injury, healthy cells surrounding the injured area attempted to proliferate, but the injured area was sending metabolic signals that prevented the kidney from effectively regenerating and repairing. ”
Arjun Deb, UCLA Professor of Medicine, Department of Molecular Biology, Cell Biology, and Developmental Biology, and Member of the Eli Edith Broad Center for Regenerative Medicine and Stem Cell Research
AD-NP1, developed by Deb’s group at UCLA with all public funding, is a monoclonal antibody engineered in the lab to mimic the function of natural antibodies produced by our immune system. Just as our immune system can produce specific antibodies that bind to and inactivate specific pathogens, the monoclonal antibody AD-NP1 was designed to target human ENPP1 and not other human proteins.
The drug was approved for phase 1 clinical trials in the heart in September. Phase 1 trials are the first step toward testing a new drug to evaluate its safety, dosing, and metabolism, and to assess its effectiveness. Deb also plans to apply for a kidney clinical trial.
The research was funded by the National Institutes of Health, the California Institute for Regenerative Medicine, and the Department of Defense.
sauce:
University of California Los Angeles
Reference magazines:
To… others. (2026). Blocking ENPP1 with a humanized monoclonal antibody promotes renal repair after acute kidney injury. cell stem cells. DOI: 10.1016/j.stem.2026.05.011. https://www.cell.com/cell-stem-cell/abstract/S1934-5909(26)00203-1
