A drug originally developed at UCLA to help heart tissue repair itself after a heart attack might also assist in repairing and regenerating damaged kidney tissues, researchers announced on June 16. The drug, called AD-NP1, was recently approved by the Food and Drug Administration for a Phase 1 clinical trial in humans. It works by blocking a protein that disrupts healing and prevents internal organs from fully recovering.
Researchers found that blocking this protein in kidney tissue accelerated repair after injury in mice. The findings were published in Cell Stem Cell and build upon years of research led by UCLA cardiovascular scientist Arjun Deb. Deb's group discovered that an injured kidney produces a protein called ENPP1, which initiates metabolic changes disrupting energy production and cell function within the injured region, impeding tissue repair.
The study showed that blocking ENPP1 enhanced kidney repair and reduced scar tissue formation, improving overall kidney function. Previous work by Deb's group indicated similar benefits when ENPP1 was blocked in heart tissue. Examination of human kidney biopsies revealed higher levels of ENPP1 expression in individuals with chronic kidney disease compared to healthy controls.
To further test their hypothesis, researchers exposed mice to diets toxic to the kidneys or administered drugs causing renal damage. Mice genetically unable to produce ENPP1 showed significantly lower levels of serum creatinine, BUN, and cystatin C—markers of renal dysfunction—after four weeks compared with control mice, indicating improved healing.
Following confirmation that inhibiting the metabolic cascade triggered by ENPP1 promoted renal recovery, researchers induced kidney damage in normal mice and treated them with AD-NP1. After seven days, these mice demonstrated improved renal function with less scarring observed upon examination.
AD-NP1 is a monoclonal antibody engineered at UCLA using public funding to mimic natural antibodies produced by the immune system but designed specifically to target human ENPP1 without affecting other proteins. The drug has been approved for Phase 1 trials evaluating safety for cardiac use; Arjun Deb plans to apply for trials assessing its potential use for kidneys as well.
