New Preclinical Research Shows Promise for Novel Treatment of Chronic Pancreatitis

April 15, 2021

UPMC Children’s Division of Pediatric Endocrinology, Diabetes, and Metabolism researcher Mohamed Saleh, MD, conducted a new study investigating a novel, nonsurgical approach to treating chronic pancreatitis and its related complications. Their study, published in February in The Journal of Clinical Investigation, details their approach and preclinical studies in mouse and nonhuman primate models of a chemical pancreatectomy designed to treat chronic pancreatitis, a condition in which there exist few treatment options that offer suboptimal results at present.

Dr. Saleh and colleagues' research tested a novel ablative approach of the exocrine pancreas using an infusion of acetic acid administered through the pancreatic duct. Not only did this approach entirely ablate the exocrine pancreas, but it also left islet cells and their function intact. Additional results obtained post-infusion showed resolution of pain associated with chronic pancreatitis and markers of chronic inflammation, which is typical in cases of chronic pancreatitis. The treatment approach also may have the ability to prevent or reverse pancreatitis-induced diabetes; however, additional research will need to be conducted by Dr. Saleh and his colleagues to prove this point.

Because the pancreatic duct can be accessed through a nonsurgical approach using endoscopic retrograde cholangiopancreatography (ECRP), this approach theoretically could be used in human subjects to deliver the acetic acid infusions, though much more work will be necessary as infusions in the preclinical models of the study were realized through an alternative surgical laparotomy due to the physically small size of the subjects.

"Our research team is extremely excited about the preliminary results we have obtained with this new approach. This would be a novel and, generally speaking, much less invasive approach to potentially rectifying cases of chronic pancreatitis and reversing its deleterious effects. Among other findings, we also noted in our subjects improved tolerance to glucose and increased insulin secretion in our in vivo studies. As clinicians, there is little we can offer our patients with chronic pancreatitis right now. If successful, this approach would dramatically alter that treatment landscape. Our team is hard at work on the next phases of our investigation," says Dr. Saleh.

Full details of the research can be found at the below reference and link. An accompanying commentary on the study appeared in the journal along with the study publication and can be accessed at the following link: Liddle RA. Chemical Pancreatectomy: An Unconventional Approach to Preventing Autodigestion in Pancreatitis. J Clin Invest. 2021 Feb 1; 131(3): e146210.

Reference

Saleh M, Sharma K, Kalsi R, Fusco J, Sehrawat A, Saloman JL, Guo P, Zhang T, Hohamed N, Wang Y, Prasadan K, Gittes GK. Chemical Pancreatectomy Treats Chronic Pancreatitis While Preserving Endocrine Function in Preclinical Models. J Clin Invest. 2021; 131(3): e143301. Epub ahead of print.

More About Dr. Saleh

Mohamed Saleh, MD, is an assistant professor at the University of Pittsburgh School of Medicine Division of Pediatric Endocrinology. His research focuses on pediatric diabetes and beta-cell biology with specific concentrations on the interaction between the exocrine and endocrine pancreas, and gene therapy to reprogram alpha cells into insulin-producing cells in type 2 diabetes mouse models.

Dr. Saleh is a member of the Center for Pediatric Research in Obesity and Metabolism (CPROM) at UPMC Children’s, which is led by scientific director and principal investigator Silva Arslanian, MD. Dr. Saleh also is a research scientist in the Gittes Lab for Diabetes and Pancreatitis Research, which is led by principal investigator George K. Gittes, MD.