Schwannoma gene therapy by adeno-associated virus delivery of
 the pore-forming protein Gasdermin-D
AbstractSchwannomas are peripheral nerve sheath tumors associated with three
                genetically distinct disease entities, namely sporadic schwannoma, neurofibromatosis
                type-2, and schwannomatosis. Schwannomas are associated with severe disability and
                in cases lead to death. The primary treatment is operative resection that itself can
                cause neurologic damage and is at times contra-indicated due to tumor location.
                Given their homogenous Schwann-lineage cellular composition, schwannomas are
                appealing targets for gene therapy. In the present study, we have generated an
                adeno-associated serotype 1 virus (AAV1)-based vector delivering N-terminal of the
                pyroptotic gene Gasdermin-D; (GSDMDNterm) under the control of the Schwann-cell
                specific promoter, P0. we have demonstrated that AAV1-P0-GSDMDNterm injection into
                intra-sciatic schwannomas reduces the growth of these tumors and resolves
                tumor-associated pain without causing neurologic damage. This AAV1-P0-GSDMDNterm
                vector holds promise for clinical treatment of schwannomas via direct intra-tumoral
                injection.