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Gene therapy of murine motor neuron disease using adenoviral vectors for neurotrophic factors
G. Haase1, P. Kennel2, B. Pettmann3, E. Vigne4, S. Akli1, F. Revah2, H. Schmalbruch5 & A.Kahn1 1INSERM Unit 129, Institut Cochin de G‚n‚tique Moleculaire, 24, rue du fb St. Jacques,75014 Paris, France 2Rh“ne-Poulenc Rorer GenCell, 13, quai JulesGuesde, 9440Vitry-sur-Seine, France 3INSERM Unit 382, Institut de Biologie duD‚veloppement de Marseille, case 907-Luminy, 13288 Marseille, France 4CNRS-PR2 URA 1301, Institut Gustave Roussy, 39, rue Camille Desmoulins, 94805 Villejuif, France 5Institute of Medical Physiology, Panum Institute, University of Copenhagen, 2200 Copenhagen N, Denmark
Correspondence should be addressed to A.K.
Motor neuron diseases such as amyotrophic lateral sclerosis (ALS) and spinalmuscular atrophy cause progressive paralysis, often leading to premature death. Neurotrophic factors have been suggested as therapeutic agents for motor neuron diseases, but their clinical use as injected recombinant protein was limited by toxicity and/or poor bioavailability. We demonstrate here that adenovirus-mediated gene
transfer of neurotrophin-3 (NT-3) can produce substantial therapeutic effects in the mouse mutant pmn (progressive motor neuronopathy). After intramuscular injection of the NT-3 adenoviral vector, pmn mice showed a 50% increase in life span, reduced loss of motor axons and improved neuromuscular function as assessed byelectromyography. These results were further improved by coinjecting an adenoviral vector coding for ciliary neurotrophic factor. Therefore, adenovirus-mediated gene transfer of neurotrophic factors offers new prospects for the treatment of motor neuron diseases.
Gene therapy for motor neuron disease
Michael Sendtner, Department of Neurology University of Wurzburg Wurzburg, D-97080, Germany
Adenoviral transfer of NT-3 and CNTF genes provides therapeutic benefit to mice with motor neuron disease (pages 429-436). |
