The researchers were able to almost completely prevent kidney injury in an animal model by changing how ceramides are made. By making a precise genetic change that affects ceramide production, the team created “super mice” that don’t get AKI, even in conditions that would otherwise trigger it.
Similarly, pre-treating mice with a new ceramide-lowering drug candidate developed by Centaurus Therapeutics, a company co-founded by Summers, prevented kidney injury. Kidney function improved, mice stayed fully active, and the kidneys looked nearly normal under the microscope. The model the researchers use tends to put the kidneys under a lot of stress, Nicholson says, so “it’s really remarkable that mice were protected from the injury.”
“These mice looked incredible,” Summers adds.
Ceramides cause kidney injury by damaging mitochondria, the part of the cell that produces energy, the researchers found. Mitochondria in injured kidney cells are visibly malformed under a microscope, and they can’t produce energy as efficiently. Tweaking how ceramides are made, either genetically or with the drug, kept mitochondria healthy and functional even under stress.