Arrest of Motor Neuron Disease in wobbler Mice Cotreated with CNTF and BDNF

• Published in: Science (American Association for the Advancement of Science) Vol. 265; no. 5175; pp. 1107 - 1110
• Main Authors: Mitsumoto, Hiroshi, Ikeda, Ken, Klinkosz, Bodgan, Cedarbaum, Jesse M., Wong, Vivien, Lindsay, Ronald M.
• Format: Journal Article
• Language: English
• Published: Washington, DC American Society for the Advancement of Science 19.08.1994; American Association for the Advancement of Science
• Subjects: Animals; Behavioral neuroscience; Biological and medical sciences; Brain-Derived Neurotrophic Factor; Ciliary Neurotrophic Factor; Drug Synergism; Drug Therapy, Combination; Forelimbs; Grade 1; Medical sciences; Mice; Mice, Mutant Strains; Motor neuron disease; Motor Neuron Disease - drug therapy; Motor Neuron Disease - pathology; Motor Neuron Disease - physiopathology; Motor neurons; Motor Neurons - drug effects; Muscle; Muscle fibers; Muscles - drug effects; Muscles - pathology; Muscular atrophy; Nerve Fibers, Myelinated - drug effects; Nerve growth factor; Nerve Growth Factors - therapeutic use; Nerve Tissue Proteins - therapeutic use; Neurons; Neurophysiology; Pharmacology. Drug treatments; Random Allocation; Vehicles; Animal model; Nervous system diseases; Rodentia; Cytokine; Motor neuron disease; Amyotrophic lateral sclerosis; Route of administration; Ciliary neurotrophic factor; Vertebrata; Mammalia; Mouse; Subcutaneous administration; Drug interaction; Degenerative disease; Brain derived neurotrophic factor; Spinal cord disease
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.8066451

Ciliary neurotrophic factor (CNTF) and brain-derived neurotrophic factor (BDNF) each promote the survival and differentiation of developing motor neurons, but do so through distinct cellular signaling pathways. Administration of either factor alone has been shown to slow, but not to arrest, progression of motor neuron dysfunction in wobbler mice, an animal model of motor neuron disease. Because CNTF and BDNF are known to synergize in vitro and in ovo, the efficacy of CNTF and BDNF cotreatment was tested in the same animal model. Subcutaneous injection of the two factors on alternate days was found to arrest disease progression in wobbler mice for 1 month, as measured by several behavioral, physiological, and histological criteria.