Partial Prevention of Cisplatin-Induced Neuropathy by Electroporation-Mediated Nonviral Gene Transfer
| Autor: | Philippe Kennel, Souad Naimi, Pierre-François Pradat, Frederic Revah, Jacques Mallet, Cecile Orsini, Françoise Finiels, Pia Delaere |
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| Rok vydání: | 2001 |
| Předmět: |
Ratón
Genetic enhancement medicine.medical_treatment Gene Expression Antineoplastic Agents Enzyme-Linked Immunosorbent Assay Gene transfer Biology Injections Intramuscular Blood Urea Nitrogen Immunoenzyme Techniques Mice Neurotrophin 3 Genetics medicine Animals Neurons Afferent Molecular Biology Cisplatin Chemotherapy Muscles Electroporation Genetic transfer Gene Transfer Techniques Peripheral Nervous System Diseases Immunology Cancer research Molecular Medicine Sensory peripheral neuropathy Plasmids medicine.drug |
| Zdroj: | Human Gene Therapy. 12:367-375 |
| ISSN: | 1557-7422 1043-0342 |
| Popis: | Cisplatin-induced sensory peripheral neuropathy is the dose-limiting factor for cisplatin chemotherapy. We describe the preventive effect of NT-3 delivery, 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 doses of plasmid DNA encoding murine NT-3 (pCMVNT-3) were tested (5 and 50 microg/animal/injection). Cisplatin-treated mice were given two intramuscular injections. The first injection of pCMVNT-3 was given 2 days before the first injection of cisplatin and the second injection 2 weeks later. Six weeks after the start of the experiment, measurement of NT-3 levels (ELISA) demonstrated significant levels both in muscle and plasma. We observed a smaller cisplatin-related increase in the latency of the sensory nerve action potential of the caudal nerve in pCMVNT-3-treated mice than in controls (p0.0001). Mean sensory distal latencies were not different between the 5- and 50- microg/animal/injection groups. Treatment with gene therapy induced only a slight muscle toxicity and no general side effects. Therefore, neurotrophic factor delivery by direct gene transfer into muscle by electroporation is of potential benefit in the prevention of cisplatin-induced neuropathy and of peripheral neuropathies in general. |
| Databáze: | OpenAIRE |
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