Partial prevention of cisplatin-induced neuropathy by electroporation-mediated nonviral gene transfer

Citation
Pf. Pradat et al., Partial prevention of cisplatin-induced neuropathy by electroporation-mediated nonviral gene transfer, HUM GENE TH, 12(4), 2001, pp. 367-375
Citations number
53
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Molecular Biology & Genetics
Journal title
HUMAN GENE THERAPY
ISSN journal
1043-0342 → ACNP
Volume
12
Issue
4
Year of publication
2001
Pages
367 - 375
Database
ISI
SICI code
1043-0342(200103)12:4<367:PPOCNB>2.0.ZU;2-Q
Abstract
Cisplatin-induced sensory peripheral neuropathy is the dose-limiting factor for cisplatin chemotherapy. We describe the preventive effect of NT-3 deli very, using direct gene transfer into muscle by in vivo electroporation in a mouse model of cisplatin-induced neuropathy. Cisplatin-induced neuropathy was produced by weekly injections of cisplatin (five injections). Two dose s of plasmid DNA encoding murine NT-3 (pCMVNT-3) were tested (5 and 50 mug/ animal/injection). Cisplatin-treated mice were given two intramuscular inje ctions. The first injection of pCMVNT-3 was given 2 days before the first i njection of cisplatin and the second injection 2 weeks later. Six weeks aft er the start of the experiment, measurement of NT-3 levels (ELISA) demonstr ated significant levels both in muscle and plasma. We observed a smaller ci splatin-related increase in the latency of the sensory nerve action potenti al of the caudal nerve in pCMVNT-3-treated mice than in controls (p < 0.000 1). Mean sensory distal latencies were not different between the 5- and 50- <mu>g/animal/injection groups. Treatment with gene therapy induced only a s light muscle toxicity and no general side effects. Therefore, neurotrophic factor delivery by direct gene transfer into muscle by electroporation is o f potential benefit in the prevention of cisplatin-induced neuropathy and o f peripheral neuropathies in general.