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Viral and non-viral gene therapy partially prevents experimental cisplatin-induced neuropathy

Gene Therapy volume 9, pages 1333–1337 (2002)Cite this article

Abstract

Sensory neuropathies are a frequent and dose-limiting complication resulting from treatment with cisplatin. Neurotrophin-3 (NT-3) promotes the survival of the large fiber sensory neurones that are impaired in cisplatin-induced neuropathy, and may therefore serve as a preventive agent. However, the short half-life of recombinant NT-3 after systemic administration limits its clinical applications. We compared two muscle-based gene transfer strategies for the continuous delivery of NT-3 to the bloodstream in an experimental model of cisplatin-induced neuropathy. Electrophysiological studies showed that the intramuscular injection of an adenovirus encoding NT-3 partially prevented the cisplatin-induced increase in sensory distal latencies. Similar effects were observed in cisplatin-treated mice that received intramuscular injections of a plasmid encoding NT-3 associated with in vivo electroporation. The two techniques were well tolerated and induced only slight muscle toxicity. Measurement of renal function, weight and survival showed that neither technique increased the toxicity of cisplatin. Our study shows that gene therapy, using either a viral or a non-viral vector, is a promising strategy for the prevention of cisplatin-induced neuropathy.

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Acknowledgements

We thank Caterine Dubertret for developing the in vivo electrotransfer technique; Isabelle Loquet, Estelle Arnould and Delphine Casanova for excellent technical support; Leïla Houhou and Sylvie Berrard for critically reading the manuscript. This work was supported by the Centre National de la Recherche Scientifique and the Institut pour la Recherche sur la Moelle Epinière (IRME).

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Author notes

  1. F Revah

    Present address: Cerep, 128 rue Danton, 92500 Rueil Malmaison, France

Authors and Affiliations

  1. Laboratoire de Génétique Moléculaire de la Neurotransmission et des Processus Neurodégénératifs (LGN), UMR C9923, Centre National de la Recherche Scientifique, Hôpital de la Pitié-Salpétrière, Paris, France

    P-F Pradat & J Mallet

  2. Fédération de Neurologie Mazarin, Hôpital de la Pitié-Salpétrière, Paris, France

    P-F Pradat

  3. Aventis Pharma Gencell, Vitry sur Seine, France

    P Kennel, S Naimi-Sadaoui, F Finiels, D Scherman, C Orsini, P Delaere & F Revah

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Pradat, PF., Kennel, P., Naimi-Sadaoui, S. et al. Viral and non-viral gene therapy partially prevents experimental cisplatin-induced neuropathy. Gene Ther 9, 1333–1337 (2002). https://doi.org/10.1038/sj.gt.3301801

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