{"id":177253,"date":"2025-11-12T21:07:11","date_gmt":"2025-11-12T21:07:11","guid":{"rendered":"https:\/\/www.europesays.com\/ie\/177253\/"},"modified":"2025-11-12T21:07:11","modified_gmt":"2025-11-12T21:07:11","slug":"new-drug-protects-mitochondria-and-prevents-kidney-injury-in-mice-theu","status":"publish","type":"post","link":"https:\/\/www.europesays.com\/ie\/177253\/","title":{"rendered":"New drug protects mitochondria and prevents kidney injury in mice \u2013 @theU"},"content":{"rendered":"

Reposted from U of U Health<\/a>.<\/p>\n

Serious damage to short-term kidney function\u2014known as acute kidney injury, or AKI\u2014can be fatal and also increase the risk of irreversible chronic kidney disease. It can be triggered by stressors ranging from sepsis to heart surgery, and it affects more than half of ICU patients. There are currently no drugs to treat this condition.<\/p>\n

\"\"<\/a>Scott Summers<\/p>\n

Now, researchers at University of Utah Health (U of U Health) have found that AKI is triggered by fatty molecules called ceramides, which damage kidney mitochondria. Using a backup drug candidate that changes ceramide metabolism, the team was able to preserve mitochondrial integrity and prevent kidney injury in mice.<\/p>\n

\u201cWe completely reversed the pathology of acute kidney injury by inactivating ceramides,\u201d said\u00a0Scott Summers<\/a>, distinguished professor and Chair of the Department of Nutrition and Integrative Physiology in the University of Utah College of Health and senior author on a paper describing the results. \u201cWe were stunned\u2014not only did kidney function stay normal, but the mitochondria were unscathed. It was truly remarkable.\u201d<\/p>\n

The results are published in\u00a0Cell Metabolism.<\/a><\/p>\n

An early warning sign for kidney injury<\/b><\/p>\n

The Summers lab had previously shown that ceramides can damage tissues ranging from heart to liver. When the team profiled ceramides in models of AKI, the correlation was striking: ceramide levels spiked sharply after kidney injury in both mice and human urine samples.<\/p>\n

\"\"<\/a>Rebekah Nicholson<\/p>\n

\u201cCeramide levels are very elevated in kidney injury,\u201d said\u00a0Rebekah Nicholson<\/a>, first author on the study, who did the research as a U graduate student in nutrition and integrative physiology and is now a postdoctoral fellow at the Arc Institute<\/a>, a nonprofit research organization in the Bay Area. \u201cThey go up quickly after damage to the kidneys, and they go up in relation to the severity of the injury. The worse the kidney injury is, the higher the ceramide levels will be.\u201d<\/p>\n

These findings suggest that urinary ceramide levels could serve as an early biomarker for AKI, helping doctors identify patients at risk\u2014such as those undergoing heart surgery\u2014before symptoms appear. \u201cIf patients are undergoing a procedure that we know puts them at high risk of AKI, then we can better predict whether or not they\u2019re actually going to have one,\u201d Nicholson said.<\/p>\n

Modifying ceramides prevents kidney injury<\/b><\/p>\n

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 \u201csuper mice\u201d that don\u2019t develop AKI, even in conditions that would otherwise trigger it.<\/p>\n

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 said, so \u201cit\u2019s really remarkable that mice were protected from the injury.\u201d<\/p>\n

\"\"<\/a>Fluorescent microscope image of the proximal tubule, the part of the kidney that\u2019s most affected by ceramides. Image credit: Luis Cede\u00f1o-Rosario<\/p>\n

\u00a0\u201cThese mice looked incredible,\u201d Summers added.<\/p>\n

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\u2019t produce energy as efficiently. Tweaking how ceramides are made, either genetically or with the drug, kept mitochondria healthy and functional even under stress.<\/p>\n

Hope for acute kidney injury and other diseases<\/b><\/p>\n

Summers emphasizes that the compound used in the study is closely related to, but not the same as, the ceramide-lowering drug that has advanced into human clinical testing. Results in mice don\u2019t always translate directly to humans, he notes, and additional studies are needed to establish safety.<\/p>\n

\u201cWe\u2019re thrilled by how protective this backup compound was, but it\u2019s still preclinical,\u201d Summers said. \u201cWe need to be cautious and do our due diligence to make sure this approach is truly safe before moving it into patients.\u201d<\/p>\n

But the researchers are optimistic. If the results hold true in humans, the researchers hope that the drug could be provided in advance to people at high risk of acute kidney injury\u2014such as patients undergoing heart surgery, about a quarter of whom experience AKI.<\/p>\n

Because the drug seems to work by keeping mitochondria healthy, the researchers suspect that it might help treat or prevent other diseases that affect mitochondria.<\/p>\n

\u201cMitochondrial problems show up in so many diseases\u2014heart failure, diabetes, fatty liver disease,\u201d Summers said. \u201cSo if we can truly restore mitochondrial health, the implications could be enormous.\u201d<\/p>\n

The results were published Nov. 12 in\u00a0Cell Metabolism\u00a0as \u201cTherapeutic Remodeling of the Ceramide Backbone Prevents Kidney Injury.<\/a>\u201d<\/p>\n

The work was supported by a NCRR Shared Instrument Grant, the Kidney Precision Medicine Project, the National Institutes of Health\u2014including the National Cancer Institute, the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute of General Medical Science\u2014the Juvenile Diabetes Research Foundation, the Burroughs Wellcome Fund for Postdoctoral Diversity Enrichment Program, the American Diabetes Association, the American Heart Association, the Margolis Foundation, and the University of Utah Diabetes and Metabolism Research Center. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.<\/p>\n

Scott Summers and Jeremy Blitzer are co-founders and shareholders of Centaurus Therapeutics, a biotech company based in San Francisco. Liping Wang is a shareholder of Centaurus Therapeutics. DN and Blitzer are listed as inventors on U.S. Patents 1177684, 11597715, and 11135207 licensed to Centaurus Therapeutics, Inc.<\/p>\n

Banner shows a panel of electron microscope images of mitochondria. Left: healthy mitochondria. Middle: badly damaged mitochondria from a kidney with AKI. Right: mitochondria treated with a drug that prevents AKI. Image credit: Rebekah Nicholson and Linda Nikolova<\/p>\n

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