Reduced Circulating ENPP1 Improves Kidney Regeneration
Researchers here report on a novel a way to improve kidney regeneration following injury, using a technique that was developed as a treatment for an injured heart. It is interesting to consider whether it might work on other tissues as well. Perhaps more relevant is the question of whether the therapy would improve ongoing tissue maintenance in an aged organ in the absence of injury; that rather depends on the fine details of the biochemistry, and could go either way.
A drug developed to help heart tissue repair itself after a heart attack might also help kidney tissue repair and regenerate, researchers have found. The drug, called AD-NP1, which was recently approved by the FDA for a Phase 1 clinical trial in humans, works in heart tissue by blocking a protein that disrupts healing and prevents internal organs from fully recovering. Researchers have now found that blocking this protein in kidney tissue speeds repair after kidney injury in mice.
An injured kidney produces a protein called ENPP1 that initiates a metabolic chain of events, disrupting energy production and function of multiple cells in the injured region, impeding tissue repair. The researchers found that blocking ENPP1 enhanced kidney repair and reduced scar tissue formation, thereby improving kidney function. Researchers previously determined that blocking ENPP1 in heart tissue improved healing.
fed mice a diet toxic to the kidneys and administered drugs that cause kidney damage to normal mice and mice with genes knocked out for producing ENPP1. Blood tests showed that these mice all had significant increases in serum creatinine, BUN, and cystatin C, which are signs of renal dysfunction. But after four weeks, these levels were greatly reduced in mice unable to produce ENPP1 compared with control mice, indicating that their kidneys were healing.
AD-NP1 is a monoclonal antibody engineered in the laboratory to mimic the function of natural antibodies produced by our immune system. Just as our immune system can produce specific antibodies to bind and inactivate specific pathogens, the monoclonal antibody AD-NP1 has been engineered to target human ENPP1 and no other human protein.
Link: https://newsroom.ucla.edu/releases/ucla-researchers-damaged-kidneys-drug