Pancreatitis is expected to be treated by alternative therapy

In a potentially clinically significant new study, researchers from Southwest Medical Center of the University of Texas and Shanghai Jiaotong University in China found that both humans and mice with pancreatitis lacked a stress hormone called fibroblast growth factor 21 (FGF21) Under normal circumstances, FGF21 is more abundant in the pancreas than in any other organ in the body They also showed that alternative therapies could reverse the disease in mice models within about 24 hours, or even stop it The relevant research results were published in the Journal of Science Translational Medicine on January 8, 2020 The title of the paper is "pancreatis is an FGF21 deficient state that is corrected by replacement therapy" The study also reported the success of a second treatment strategy A potential drug called perk inhibitor targets different steps in integrated stress response (ISR) Integrated stress is a cellular pathway that affects the amount of FGF21 available in the pancreas Dr David mangelsdorf, co-author of the paper, said, "given that several FGF21 candidates are being or will be used in clinical trials to treat metabolic related diseases, it is possible to test whether FGF21 can be used in the treatment of human pancreatitis in the near future." Pancreatitis is a debilitating and sometimes fatal pancreatitis, which can be acute or chronic About 275 thousand American hospitalized patients are admitted each year, and the incidence rate of this disease is increased due to unclear reasons According to the National Institute of diabetes, digestive disease and kidney disease (NIDDK), affiliated to the National Institutes of Health (NIH), many causes of pancreatitis include chronic drinking, stones and some genetic diseases Pancreatitis can also occur as a complication of endoscopic retrograde cholangio pancreatography (ERCP) In this operation, cameras, contrast media, and X-rays are used to examine the bile duct, gallbladder, and pancreatic duct The treatment of acute pancreatitis is usually supportive Most of the patients recovered after a few days in hospital, where they received intravenous fluids and pain relief Chronic pancreatitis is more common in patients with alcohol abuse, but it will worsen over time Progressive damage to pancreatic tissue can affect the ability to digest food, sometimes prescription enzymes are needed to avoid malnutrition The pancreas is an organ near the small intestine that produces insulin, which helps to maintain blood sugar balance Mangelsdorf said the organ also produces enzymes that are normally released into the small intestine to aid digestion In the past two decades, these researchers have studied FGF21 and learned valuable information about this important metabolic hormone In 2017, the researchers reported the role of the hormone in preventing digestive enzymes from damaging the pancreas "We found that FGF21 stimulated the pancreas to secrete digestive enzymes into the small intestine," mangelsdorf said If this mechanism does not work, these digestive enzymes will remain in the pancreas, where they will destroy the tissue and cause inflammation " Mangelsdorf said his lab and others have shown that the absence of FGF21 in animal models of pancreatitis magnifies tissue damage and slows recovery This made him and his colleagues from Pittsburgh University, Stanford University and Shanghai Jiaotong University want to know whether the stress hormone might be used to treat pancreatitis To answer this question, the researchers studied the effect of pancreatitis on the FGF21 pathway by analyzing pancreatic samples from mice and humans with acute and chronic pancreatitis They found in mice that FGF21 levels in the pancreas increased during the first four hours of pancreatitis, and unexpectedly decreased at the 12th hour, barely detectable after 18 hours FGF21 also decreased in human pancreatitis They were able to confirm that FGF21 plays a similar role in three different mouse models of the disease: cerulein induced pancreatitis, which causes excessive secretion of pancreatic enzymes; alcohol induced pancreatitis and ERCP induced pancreatitis These experiments confirm that the absence of FGF21 is a characteristic of this disease Next, they wanted to know if FGF21 replacement therapy was effective in these three pancreatitis mouse models The researchers used each of the three mouse models to conduct multiple experiments, repeated three to four times for each mouse model, with three to eight mice in each mouse test group They also tested 66 samples of human tissue - 14 from healthy people and 52 from people with pancreatitis Four injections of 1 mg of FGF21 per kilogram of mouse body weight within 12 to 16 hours after drug or alcohol induced pancreatitis increased the level of FGF21 in the blood, leading to inflammation, necrosis and swelling, and most of these symptoms disappeared within 24 hours To see if they could somehow prevent ERCP induced pancreatitis, the researchers mixed FGF21 with the contrast medium commonly used in the process and found that doing so could maintain normal FGF21 levels and prevent their decline, thus preventing the resulting inflammation Mangelsdorf cautioned that the limitations of this study include mouse models that mimic but do not fully reproduce human disease, and that clear conclusions about human pancreatitis will need to be analyzed in more subjects "Nevertheless, we found that pancreatitis is widely described as a state of absence of FGF21, which can be reversed or prevented by drug recovery," he said