Abstract
Attempts to develop clinical treatments for neuropathy using neurotrophins have not been successful. We tested whether neurotrophin gene delivery to dorsal root ganglia (DRGs) using non-replicating herpes simplex virus (HSV)-based vectors could prevent the development of neuropathy caused by administration of cisplatin. Following subcutaneous inoculation of HSV vectors expressing nerve growth factor (NGF) or neurotrophin-3 (NT-3), neurons in the DRG were transduced to produce NGF or NT-3 in vivo. Inoculation of either the NGF- or the NT-3-expressing vectors 3 days before the start of a 6-week course of cisplatin treatment protected against cisplatin-induced neuropathy assessed by electrophysiological, histological and behavioural measures 2 months later. Iatrogenic neuropathy caused by administration of chemotherapeutic drugs represents an excellent target for a human trial to assess the potential of gene therapy to prevent neuropathy.
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