Pancreatitis is an inflammatory disease of the pancreas that results in significant morbidity, mortality, and hospitalizations. Ongoing injury to pancreas, e.g., ongoing alcohol abuse, results in continued inflammation of pancreas and damage to the pancreatic tissue. This results in a healing response that results in excessive fibrosis, akin to a chronic wound. Damage to the pancreas results in insufficient pancreatic function, i.e., insufficient digestive enzymes as well as insufficient insulin production leading to diabetes. Patients with chronic pancreatitis also have unbearable pain, which can lead to spiral of drug abuse and alcoholism with accompanying social and economic consequences. Unfortunately, our military personnel and Veteran population bear significant brunt of this disease due to high prevalence of the etiologic factors including alcoholism, smoking, and drug abuse. Despite the evident need, there is no specific therapy for chronic pancreatitis owing to our incomplete understanding of the pathophysiology of the disease.

While our understanding of the pathophysiology of chronic pancreatitis is still evolving, excessive fibrosis on microscopic examination is a hallmark of chronic pancreatitis. Specialized cells present in the pancreas called pancreatic stellate cells (PSC) are now considered key to the fibrosis observed in chronic pancreatitis. Interestingly, the biology of fibrosis is very similar in all organs, whether fibrosis is in liver due to cirrhosis or in lungs (in a disease called Idiopathic Pulmonary Fibrosis, or IPF). Thus, the research and novel therapies developed for treatment of fibrosis in one disease may be applicable to disease with fibrosis arising at another site. Recently, Pirfenidone, a novel drug, has been developed and evaluated as a treatment for IPF, with promising results. In multiple clinical trials, Pirfenidone treatment has been shown to effectively treat IPF and improve survival. In animal studies, Pirfenidone has shown good efficacy against fibrosis of lung, liver, kidney fibrosis, as well as good activity against stellate cells. However, Pirfenidone has never been tested in animal models of chronic pancreatitis. Given that stellate cells play a major role in chronic pancreatitis, in the current proposal we will evaluate the efficacy of Pirfenidone against chronic pancreatitis in multiple animal models.

If our proposed studies suggest that Pirfenidone is effective against chronic pancreatitis, it will be possible to do a clinical trial of Pirfenidone in chronic pancreatitis relatively soon. Due to the proposed studies, an effective therapy for chronic pancreatitis may be able to reach clinics soon. This would be life-changing for patients with chronic pancreatitis, a very painful disease for which no relief is currently available.