Treatment with trkC agonist antibodies delays disease progression in neuromuscular degeneration (nmd) mice

Hum Mol Genet. 2005 Jul 1;14(13):1825-37. doi: 10.1093/hmg/ddi189. Epub 2005 May 11.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / administration & dosage*
  • Antibodies, Monoclonal / immunology
  • Disease Models, Animal
  • Humans
  • Mice
  • Mice, Neurologic Mutants
  • Muscular Atrophy, Spinal / complications
  • Muscular Atrophy, Spinal / drug therapy*
  • Muscular Atrophy, Spinal / pathology
  • Receptor, trkC / antagonists & inhibitors*
  • Receptor, trkC / immunology
  • Signal Transduction / drug effects

Substances

  • Antibodies, Monoclonal
  • Receptor, trkC