Effects of cardiotrophin-1 (CT-1) in a mouse motor neuron disease
Cardiotrophin‐1 (CT‐1) has potent survival‐promoting effects on motor neurons in vitro and in vivo and may be effective in treating motor neuron diseases (MND). We investigated the effects of CT‐1 treatment in wobbler mouse MND. Wobbler mice were randomly assigned to receive subcutaneously injected...
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Published in | Muscle & nerve Vol. 24; no. 6; pp. 769 - 777 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
New York
John Wiley & Sons, Inc
01.06.2001
Wiley |
Subjects | |
Online Access | Get full text |
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Summary: | Cardiotrophin‐1 (CT‐1) has potent survival‐promoting effects on motor neurons in vitro and in vivo and may be effective in treating motor neuron diseases (MND). We investigated the effects of CT‐1 treatment in wobbler mouse MND. Wobbler mice were randomly assigned to receive subcutaneously injected CT‐1 (1 mg/kg, n = 18, in two experiments) or vehicle (n = 18, in two experiments) daily, 6 times/week for 4 weeks after clinical diagnosis at age 3 to 4 weeks. Cardiotrophin‐1 treatment prevented deterioration in paw position and walking pattern abnormalities. Grip strength declined steadily in the vehicle group, whereas in the CT‐1 group it declined at week 1 but increased thereafter to exceed baseline strength by 5% (P = 0.0002) at week 4. Running speed was faster with CT‐1 (P = 0.007). Biceps muscle twitch tension, muscle weight, mean muscle fiber diameter, and intramuscular axonal sprouting were significantly greater with CT‐1 treatment than with vehicle treatment. Histometry revealed a trend that indicated CT‐1 modestly increased the number of immunoreactive motor neurons, as determined by both choline acetyltransferase and c‐Ret antibodies, and reduced the number of phosphorylated neurofilament immunoreactive perikarya (P = 0.05). The number of large myelinated motor axons significantly increased with treatment (206 versus 113, P = 0.01). We conclude that CT‐1 exerts myotrophic effects as well as neurotrophic effects in a mouse model of spontaneous MND, a finding that has potential therapeutic implications for human MND. © 2001 John Wiley & Sons, Inc. Muscle Nerve 24: 769–777, 2001 |
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Bibliography: | ALS Association ark:/67375/WNG-2V8H0MWD-H istex:CE9D68358FD0D22A57E2D928FB4AB9D13740CC22 ArticleID:MUS1068 National Institutes of Health - No. K08-NS01846-03 ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0148-639X 1097-4598 |
DOI: | 10.1002/mus.1068 |