title: Treatment with trkC agonist antibodies delays disease progression in neuromuscular degeneration (nmd) mice.
abstract: 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.
authors.affiliation: Department of Physiology and Biophysics, School of Medicine, University of Seville, Seville, Spain.
authors.forename: Rocio
authors.initials: R
authors.lastname: Ruiz
authors.forename: John
authors.initials: J
authors.lastname: Lin
authors.forename: Alison
authors.initials: A
authors.lastname: Forgie
authors.forename: Davide
authors.initials: D
authors.lastname: Foletti
authors.forename: David
authors.initials: D
authors.lastname: Shelton
authors.forename: Arnon
authors.initials: A
authors.lastname: Rosenthal
authors.forename: Lucia
authors.initials: L
authors.lastname: Tabares
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000276:immunology; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D008818:Mice, Neurologic Mutants; D009134:Muscular Atrophy, Spinal / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D020812:Receptor, trkC / Q000037:antagonists & inhibitors* / Q000276:immunology; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000911:Antibodies, Monoclonal; D020812:Receptor, trkC