Mechano-growth factor, an IGF-I splice variant, rescues motoneurons and improves muscle function in SOD1 mice |
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| Authors: | Joanna Riddoch-Contreras Shi-Yu Yang James RT Dick Geoffrey Goldspink Richard W Orrell Linda Greensmith |
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| Institution: | aSobell Department of Motor Neuroscience and Movement Disorders, Institute of Neurology, UCL, Queen Square, London WC1N 3BG, UK;bUniversity Department of Surgery, Royal Free and University College Medical School, UCL, Rowland Hill Street, London NW3 2PF, UK;cDepartment of Clinical Neuroscience, Institute of Neurology, UCL, Rowland Hill Street, London NW3 2PF, UK |
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| Abstract: | Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by motoneuron degeneration. Although viral delivery of IGF-I has shown therapeutic efficacy in the SOD1G93A mouse model of ALS, clinical trials of IGF-I in ALS patients have led to conflicting results. Here we examine the effects of an IGF-I splice variant, mechano-growth factor (MGF) which has previously been shown to have greater neuroprotective effects than IGF-I in a number of models of neurodegeneration. A mammalian expression plasmid containing either MGF or, for comparison, the IGF-I cDNA sequence was delivered to the hindlimb muscles of SOD1G93A mice at 70 days of age, at symptom onset. Treatment with either IGF-I or MGF resulted in a significant improvement in hindlimb muscle strength, and an increase in motor unit and motoneuron survival. Significantly more motoneurons survived in MGF treated mice. |
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| Keywords: | Neurotrophic factors Motoneuron survival Motor neuron disease Therapy Skeletal muscle Neuroprotection Amyotrophic lateral sclerosis IGF-I MGF |
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