Spinal muscular atrophy with respiratory distress type 1 (SMARD1) is a fatal hereditary disease of autosomal recessive trait in infants. It is chararterised by degeneration of lower motor neurons and associated progressive muscle paralysis, for which there is no known cure. The phenotype of nmd (neuromuscular degeneration) mice closely resembles the human SMARD1, with progressive paralysis of extremities and diaphragm leading to premature death. The identification of the mouse gene responsible for nmd, Ighmbp2, has been critical for the identification of the genetic defect in humans. We have studied the nmd mouse model with in vivo electrophysiological techniques and evaluated the ability of 2256, a monoclonal antibody with agonist effect on tyrosine kinase receptor C (trkC) to ameliorate the neurodegenerative symptoms caused by mutant Ighmbp2 in nmd mice. Upon treatment with 2256, a significant but transitory improvement of muscular strength was observed in nmd mice, as well as normalization of the amount of neuromuscular depression during high frequency nerve stimulation. These results suggest that the use of monoclonal agonist antibodies for neurotrophin receptors may have therapeutic potential in lower motor neuron diseases such as SMARD1. Downloaded fro
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