Combined Restitutive Therapy for Treatment of Immunosuppressive Refractory Crohn Disease

Abstract

Crohn’s Disease (CD) is believed to be the result of dys-regulated interactions between a genetically susceptible host and their commensal gut microbiota (1). CD affects over 600,000 Americans and treatment still faces many challenges (2). Pharmacotherapy centers on the use of anti-inflammatories and immunosuppressants (3). However, a sub-set of patients with CD are refractory to immunosuppressive therapy. Recent studies have implicated defects in autophagy and bacterial killing as a possible etiology leading to host-microbe dysregulation (4). This could explain the lack of response to immunosuppression seen in these CD patients. A recent study in adults with CD showed the potential for granulocyte-macrophage colony stimulating factor (GM-CSF) to enhance bacterial killing and restore intestinal homeostasis (5), but very little data exists in pediatric patients (6). Another study reports a role for low-dose naltrexone (LDN, a mu opioid antagonist) in helping restore the epithelial barrier in active CD (7). The mechanism of action of LDN is thought to be through activation of endogenous opioid signaling (8). Recent murine studies have shown that direct mu opioid receptor (MOR) activation can enhance intestinal epithelial healing and prevent epithelial apoptosis (9). Here, we report a combined intestinal-restitutive approach using GM-CSF and loperamide (a peripheral MOR agonist) to induce and maintain remission in a 17-year-old CD patient.