Experimental Heart Drug Shows Promise In Repairing Damaged Kidneys — New Study

 

A drug originally developed to help the heart heal after a heart attack may also speed up recovery from kidney injury, according to new research from the University of California, Los Angeles (UCLA).

The study, published in Cell Stem Cell, found that the experimental drug, known as AD-NP1, improved kidney repair and reduced scarring in mice by blocking a protein that interferes with the body’s natural healing process.

The findings raise hopes that the treatment, which has already been cleared by the U.S. Food and Drug Administration (FDA) to begin Phase 1 clinical trials for heart

disease, could eventually be tested as a therapy for kidney disease.

Researchers identified a protein called ENPP1 as a major obstacle to kidney regeneration after injury. They found that damaged kidneys produce high levels of the protein, triggering metabolic changes that disrupt energy production and prevent healthy cells from repairing injured tissue.

“When the kidney is injured, nearby healthy cells attempt to regenerate, but signals from the damaged tissue stop that repair process,” said senior author Dr Arjun Deb, professor of medicine and molecular, cell and developmental biology at UCLA. “We found that blocking ENPP1 removes that barrier and allows the kidney to heal more effectively.”

The discovery builds on previous work by Deb’s laboratory, which showed that ENPP1 also limits the heart’s ability to repair itself after injury.

To investigate whether the same mechanism operates in the kidneys, the researchers first examined tissue samples from people with chronic kidney disease. They found significantly higher levels of ENPP1 compared with healthy kidney tissue.

The team then induced kidney injury in mice using a kidney-toxic diet and drugs. Mice genetically engineered to lack ENPP1 recovered more quickly than normal animals, showing lower levels of blood markers associated with kidney damage, including serum creatinine, blood urea nitrogen (BUN), and cystatin C.

Researchers next tested AD-NP1, a laboratory-engineered monoclonal antibody designed to specifically block ENPP1. Mice treated with the drug after kidney injury had better kidney function within a week and developed substantially less scar tissue than untreated animals.

“These animals had a far better outcome,” Deb said. “Their kidneys were less damaged, and kidney cells were proliferating more.”

AD-NP1 was developed entirely at UCLA using public funding. Unlike conventional drugs, it is a monoclonal antibody engineered to target only the ENPP1 protein, leaving other proteins unaffected.

The FDA approved the drug last year to enter Phase 1 clinical trials for heart disease, where researchers will evaluate its safety and appropriate dosing in humans. Deb and his colleagues now hope to expand development to include kidney disease.

Although the latest findings are limited to animal studies, they suggest that targeting ENPP1 could offer a new strategy for treating acute kidney injury and possibly slowing the progression of chronic kidney disease, which affects hundreds of millions of people worldwide.

The researchers caution that further studies are needed to determine whether the treatment produces similar benefits in humans. If successful, the approach could represent a new class of regenerative therapies capable of helping multiple organs recover after injury.