LAUSR

OBJECTIVE Schwannomas are benign tumors that arise from Schwann cells of the nerve sheath, and their management presents a significant clinical challenge, particularly in genetic conditions like NF2-related schwannomatosis (NF2-SWN). Although current treatments, including surgery, radiation, and repurposed pharmacological agents, can be effective, they are often limited by issues such as tumor recurrence and the risk of nerve function impairment. This study aims to evaluate the potential of recombinant human Neuregulin1 beta 1 (rhNRGβ1) to inhibit schwannoma growth and promote Schwann cell differentiation in preclinical models. METHODS We investigated the therapeutic potential of rhNRGβ1, a recombinant human epidermal growth factor (EGF)-like domain of Neuregulin1 beta 1, as a growth-inhibitory agent for schwannomas. Two distinct mouse models were used to assess its efficacy, with both histological and functional endpoints analyzed. RESULTS Both systemic and local administration of rhNRGβ1 resulted in a significant reduction in schwannoma tumor growth. Mechanistically, rhNRGβ1 not only inhibited tumor proliferation, but also promoted the differentiation of both proliferative and de-differentiated Schwann cells, suggesting a dual action of growth inhibition and cellular maturation. INTERPRETATION These findings highlight the therapeutic potential of rhNRG1-β1 in managing schwannomas, not only by reducing tumor growth, but also by promoting the maturation and functional restoration of Schwann cells. This dual effect provides a promising avenue for novel therapeutic strategies aimed at addressing both the growth and cellular differentiation challenges associated with schwannomas in NF2-SWN and other related conditions. ANN NEUROL 2025.