Mechano-growth factor, an IGF-I splice variant, rescues motoneurons and improves muscle function in SOD1(G93A) mice.
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 SOD1(G93A) 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 SOD1(G93A) 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.
Riddoch-Contreras
Joanna
J
Sobell Department of Motor Neuroscience and Movement Disorders, Institute of Neurology, UCL, Queen Square, London WC1N 3BG, UK.
Yang
Shi-Yu
SY
Dick
James R T
JR
Goldspink
Geoffrey
G
Orrell
Richard W
RW
Greensmith
Linda
L
D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics / Q000503:physiopathology* / Q000628:therapy*; D000818:Animals; D002452:Cell Count; D004195:Disease Models, Animal; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis / Q000235:genetics / Q000627:therapeutic use*; D007551:Isotonic Contraction / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000187:drug effects* / Q000502:physiology; D018763:Muscle Fatigue / Q000187:drug effects / Q000502:physiology; D053580:Muscle Strength / Q000187:drug effects / Q000502:physiology; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D009929:Organ Size / Q000187:drug effects / Q000502:physiology; D013385:Succinate Dehydrogenase / Q000378:metabolism; D013482:Superoxide Dismutase / Q000235:genetics*
C527564:mechano-growth factor, mouse; D007334:Insulin-Like Growth Factor I; C109415:SOD1 G93A protein; D013482:Superoxide Dismutase; D013385:Succinate Dehydrogenase