Screening Trial for Pain Relief in Schwannomatosis (STARFISH)

Schwannomatosis (SWN) is a rare tumor suppressor syndrome (estimated prevalence of 1/126,315) characterized by the predisposition to develop on-intradermal schwannomas. Chronic pain is the most common symptom of SWN and usually persists despite aggressive surgical and medical management. The etiology of pain in SWN is not clear, and the development of novel treatments for SWN and related pain has been extremely slow and inefficient. To date, virtually no agents have passed through the development pathway to enter clinical trials for SWN patients. Recognizing that one of the biggest challenges in basic and translational SWN research is the lack of clinically-relevant models, we successfully established five patient-derived SWN cell lines and an orthotopic patient-derived xenograft (PDX) tumor mouse model. In SWN patient samples and in PDX tumors, we found evidence of elevated neuroinflammatory signaling - SWN tumor cells prime macrophages to produce inflammatory cytokines. These inflammatory cytokines, including interleukin-6 (IL-6), induce calcitonin gene-related peptide (CGRP) in dorsal root ganglia sensory neurons, thereby contributing to the development of pain. Our proposed study will leverage these exciting findings and utilize state-of-the-art molecular and genetic approaches and our clinically relevant SWN models to improve treatment of SWN. Hypothesis: We hypothesize that erenumab-aooe, an anti-CGRP receptor monoclonal antibody, will be.