Functional improvement in mouse models of familial amyotrophic lateral sclerosis by PEGylated insulin-like growth factor I treatment depends on disease severity
| العنوان: | Functional improvement in mouse models of familial amyotrophic lateral sclerosis by PEGylated insulin-like growth factor I treatment depends on disease severity |
|---|---|
| المؤلفون: | Mark R. Nilges, Susanne Ostrowitzki, Heidemarie Kletzl, Susanne Schroeder, Taleen Hanania, Andreas Hoeflich, Bettina Holtmann, Will Spooren, Stefanie Saenger, Michael Sendtner, Friedrich Metzger |
| المصدر: | Amyotrophic Lateral Sclerosis. 13:418-429 |
| بيانات النشر: | Informa UK Limited, 2012. |
| سنة النشر: | 2012 |
| مصطلحات موضوعية: | Male, Genetic enhancement, medicine.medical_treatment, Mice, Transgenic, Disease, Pharmacology, Severity of Illness Index, Mice, medicine, Animals, Dosing, Insulin-Like Growth Factor I, Amyotrophic lateral sclerosis, Motor Neurons, business.industry, Growth factor, Amyotrophic Lateral Sclerosis, General Medicine, Motor neuron, Spinal cord, medicine.disease, Motor coordination, Disease Models, Animal, medicine.anatomical_structure, Neurology, Disease Progression, Neurology (clinical), business, Neuroscience |
| الوصف: | Insulin-like growth factor I (IGF-I) has been successfully tested in the SOD1-G93A mouse model of familial amyotrophic lateral sclerosis (ALS) and proposed for clinical treatment. However, beneficial effects required gene therapy or intrathecal application. Circumventing the dosing issues we recently found that polyethylene glycol (PEG) modified IGF-I (PEG-IGF-I) modulated neuromuscular function after systemic application, and protected against disease progression in a motor neuron disease model. Here we investigated its effects in two SOD1-G93A mouse lines, the G1L with a milder and the G1H with a more severe phenotype. Results showed that in G1L mice, PEG-IGF-I treatment significantly improved muscle force, motor coordination and animal survival. In contrast, treatment of G1H mice with PEG-IGF-I or IGF-I even at high doses did not beneficially affect survival or functional outcomes despite increased signalling in brain and spinal cord by both agents. In conclusion, the data point towards further investigation of the therapeutic potential of PEG-IGF-I in ALS patients with less severe clinical phenotypes. |
| تدمد: | 1471-180X 1748-2968 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::594b69f91bb97c330f6c18a2c72c4ac2Test https://doi.org/10.3109/17482968.2012.679944Test |
| رقم الانضمام: | edsair.doi.dedup.....594b69f91bb97c330f6c18a2c72c4ac2 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 1471180X 17482968 |
|---|