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• W2020557756 abstract "Based on its potent neurotrophic and myotrophic activities, insulin-like growth factor I (IGF-I) has been proposed for treatment of neuromuscular disorders such as muscular dystrophies and amyotrophic lateral sclerosis (ALS). However, the short half life in the circulation limits its use in vivo. At least in mouse models, beneficial effects are generally only observed by dosing regimens such as minipumps or gene therapy that are difficult to translate to patients. We have developed a polyethylene glycol coupled IGF-I (PEG-IGF-I) that could circumvent these problems by longer half-life, showing all features of a therapeutic agent supporting muscular and neuronal function. Here we investigated its effects in the pmn mutant mouse, a model with typical dying-back motoneuron degeneration. In vitro, PEG-IGF-I and rhIGF-I profoundly promoted survival axonal growth of wild-type as well as pmn mutant embryonic motoneurons, suggesting that PEG-IGF-I had a fully conserved neurotrophic activity via its receptor. In vivo, treatment of pmn mutant mice with PEG-IGF-I prolonged survival, protected against late stage weight loss and significantly maintained muscle force and motor coordination. Consistently, PEG-IGF-I treatment rescued facial and lumbar motoneurons from cell death and partially preserved phrenic nerve myelinated axons. The data support that PEG-IGF-I could be used for treatment of neuromuscular diseases in a clinically feasible manner." @default.
• W2020557756 created "2016-06-24" @default.
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• W2020557756 date "2011-12-01" @default.
• W2020557756 modified "2023-09-24" @default.
• W2020557756 title "Therapeutic effects of PEGylated insulin-like growth factor I in the pmn mouse model of motoneuron disease" @default.
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• W2020557756 doi "https://doi.org/10.1016/j.expneurol.2011.09.015" @default.
• W2020557756 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/21963648" @default.
• W2020557756 hasPublicationYear "2011" @default.
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