Researchers have uncovered a molecular pathway that appears to block kidney regeneration after injury.
The body’s ability to repair damaged organs is surprisingly limited, especially after serious injuries to the heart or kidneys. Now, UCLA researchers have found that a drug originally developed to help heart tissue regenerate after a heart attack may also accelerate kidney repair, raising the possibility of a new treatment approach for one of the world’s leading causes of chronic disease.
The drug, AD-NP1, recently received FDA approval to enter a Phase 1 clinical trial for heart disease. Researchers have now shown that it can also improve recovery from kidney injury in mice by blocking a protein that interferes with the body’s natural healing process.
The findings, published in Cell Stem Cell, build on years of research from the laboratory of UCLA cardiovascular scientist Arjun Deb.
ENPP1 Identified as a Key Barrier to Kidney Regeneration
Deb’s team found that injured kidneys produce a protein called ENPP1, which triggers a metabolic chain reaction. This disrupts energy production and the function of several cell types in the damaged area, slowing tissue repair. Blocking ENPP1 improved kidney healing, lowered scar tissue formation, and strengthened kidney function. The group had previously shown that blocking ENPP1 also improved healing in the heart.
The researchers studied kidney biopsies from people with chronic kidney disease and found higher ENPP1 levels than in healthy tissue. They then fed mice a kidney-toxic diet and gave kidney-damaging drugs to both normal mice and mice genetically unable to produce ENPP1.
Blood tests showed that all the mice initially had sharp increases in serum creatinine, BUN, and cystatin C, which are markers of kidney dysfunction. After four weeks, however, those levels fell much more in mice that could not produce ENPP1 than in control mice, suggesting that their kidneys were recovering.
AD-NP1 Accelerates Kidney Healing in Mice
After confirming that blocking the ENPP1-driven metabolic pathway improved kidney repair, the scientists damaged the kidneys of normal mice and treated them with AD-NP1. Seven days later, the treated mice had better kidney function, and later kidney examinations showed less scarring.
“These animals had a far better outcome. Their kidneys were not as damaged, and the kidney cells were proliferating more,” said Deb, who is a UCLA professor of medicine and molecular, cell and developmental biology, and a member of the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research.
“We found that the same mechanisms we observed in the heart were also applicable in the kidney. After injury, healthy cells around the damaged area were trying to proliferate, but the damaged area was sending metabolic signals that prevented the kidney from regenerating and repairing effectively.”
Monoclonal Antibody Targets ENPP1 for Organ Repair
AD-NP1 was developed entirely at UCLA by Deb’s group using public funding. It is a monoclonal antibody, a lab-engineered protein designed to act like the natural antibodies made by the immune system. While the immune system produces antibodies that bind to and disable specific pathogens, AD-NP1 was engineered to target human ENPP1 and no other human protein.
The FDA approved AD-NP1 in September for Phase 1 human clinical trials in the heart. Phase 1 trials test a new drug’s safety, dosing, and metabolism before later studies examine whether it works. Deb also plans to seek approval for kidney trials.
Reference: “ENPP1 blockade with a humanized monoclonal antibody enhances renal repair after acute kidney injury” by Lianjiu Su, Qihao Sun, Ziheng Zhou, Rending Wang, Junqiang Wang, Juan Felipe Alvarez, Bo Tao, Kiran Das, Qiuyuan Zhou, Jing Wang, Guanglin Zhang, Johanna ten Hoeve, Linlin Zhang, Calvin Pan, Qiang Du, Hooman Allayee, Zhihao Liu, Ilya Savchenko, Shan Kou, Jijun Wan, Matteo Pellegrini, Aldons J. Lusis, Thomas Graeber, Shen Li and Arjun Deb, 16 June 2026, Cell Stem Cell.
DOI: 10.1016/j.stem.2026.05.011
The research was funded by the National Institutes of Health, the California Institute of Regenerative Medicine and the Department of Defense.
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