Human Molecular Genetics Advance Access originally published online on May 11, 2005
Human Molecular Genetics 2005 14(13):1825-1837; doi:10.1093/hmg/ddi189
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Treatment with trkC agonist antibodies delays disease progression in neuromuscular degeneration (nmd) mice
1Department of Physiology and Biophysics, School of Medicine, University of Seville, Seville, Spain and 2Rinat Neuroscience Corporation, 3155 Porter Drive, Palo Alto, CA 94304, USA
* To whom correspondence should be addressed. Tel: +34 954556574; Fax: +34 954551769; Email: ltabares{at}us.es
Received January 17, 2005; Accepted May 4, 2005
Spinal muscular atrophy with respiratory distress type 1 (SMARD1) is a fatal autosomal recessive disorder seen in infants. It is characterized by lower motor neuron degeneration, progressive muscle paralysis and respiratory failure, for which no effective treatment exists. The phenotype of neuromuscular degeneration (nmd) mice closely resembles the human SMARD1. The identification of the mutated mouse gene in nmd mice, Ighmbp2, led to the discovery of mutations of the homologous gene in humans with SMARD1. We have studied the nmd mouse model with in vivo electrophysiological techniques and evaluated the efficacy of Mab2256, a monoclonal antibody with agonist effect on the tyrosine kinase receptor C, trkC, on disease progression in nmd mice. Treatment with Mab2256 resulted in a significant but transient improvement of muscle strength in nmd mice, as well as normalization of the neuromuscular depression during high-frequency nerve stimulation. These results suggest the potential of using monoclonal agonist antibodies for neurotrophin receptors in lower motor neuron diseases such as SMARD1.