SPARK scholar Sohail Husain and team identify novel role for retinoids in pancreatitis

SPARK scholar Sohail Husain and team identify novel role for retinoids in pancreatitis

Posted on March 30th, 2023

Vitamin A could prevent the life-threatening, painful inflammatory disorder of the pancreas called pancreatitis, suggests a new study from SPARK Scholar Sohail Husain, MD, and colleagues. The researchers published their findings in Science Translational Medicine identifying a therapeutic role for retinoids – vitamin A and its analogs.

The paper is the first to implicate the unexpected finding of a beneficial role for the micronutrient vitamin A, found in carrots and other foods, in preventing pancreatitis. Almost half a million Americans develop pancreatitis each year, and one in ten of them are children. The study originates from the research laboratory of Dr. Husain, Chief of the Stanford Division of Gastroenterology, Hepatology, and Nutrition in the Department of Pediatrics and Stanford Medicine Children’s Hospital, and the inaugural Chambers-Okamura Endowed Professor of Pediatric Gastroenterology at Stanford University.

Dr. Husain’s team set out to identify factors involved in a form of pancreatitis that is an adverse drug outcome of asparaginase, a commonly used anti-cancer drug. Asparaginase is primarily used as integral chemotherapy for acute lymphoblastic leukemia (ALL), the most common cancer in children. The collaborative team of researchers discovered that asparaginase users (all of them children with ALL) who serendipitously took vitamin A as a medicine were protected against pancreatitis.

The studies used several approaches, included screening millions of sets of large data from FDA and patient electronic health records, utilizing two independent patient cancer registries (some of which tracked dietary nutrient intake), computational modeling of molecules that would predict benefit with asparaginase exposure or in pancreatitis, and performing laboratory studies in pancreas cells with vitamin A treatment. All of the studies pointed to a benefit of vitamin A in combating pancreatitis.

This is the first set of studies to link the potential nutritional intervention of vitamin A to pancreas health and disease prevention. Further clinical trials are needed to evaluate whether dietary vitamin A or supplementation is ideal, the exact regimen to give, the mechanism of benefit for pancreatitis prevention, and whether the results are generalizable, as the researchers’ data suggest, to multiple pancreatitis causes or other inflammatory conditions that are similar to pancreatitis.

SPARK founder and co-director Daria Mochly-Rosen, PhD, said that the study’s findings are especially exciting, “since they are easy to implement and affect an important and debilitating disease.”

Dr. Husain noted that while this study was not directly part of his SPARK project, “we were nonetheless influenced by the points we learned in SPARK about translational impact and innovation, and, in the case of the paper, to consider novel retinoids to prevent pancreatitis and potentially be broadly beneficial to other inflammatory diseases.”

The research underscores the importance of team science, Dr. Husain added. Along with Dr. Husain on the study is co-senior author Anil Jegga, PhD, from Cincinnati Children’s Hospital. The study was coordinated by a senior scientist at Stanford in the Husain Lab, Olivia Tsai, PhD. Additional co-authors are from other institutions including the Dana-Farber Cancer Institute, Rutgers University, the University of Pittsburgh, CHU Sainte-Justine in Montreal, and Columbia University.