Abstract
Before potential therapeutic strategies for the treatment of amyotrophic lateral sclerosis (ALS) can be advanced to human clinical trials, there is a need to assess them in an animal model that best resembles the disease process. SOD1 G93A mice have close resemblance to familial ALS (fALS) and have been used in this study to evaluate the therapeutic potential of leukaemia inhibitory factor (LIF). LIF action was investigated by assessing three delivery methods: (1) daily subcutaneous injection; (2) through LIF rods placed adjacent to hind limb skeletal muscle and (3) continuous intrathecal infusion. The effect on disease progression was assessed by semi-quantitative and quantitative functional measurements, and histologically on the survival of motor neurons and number of reactive astrocytes. The results show that LIF had no beneficial effects when administered using the three methods of drug delivery. These results suggest that further evaluation of LIF in this transgenic model is required to fully characterize its' therapeutic potential.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amyotrophic Lateral Sclerosis / drug therapy*
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Amyotrophic Lateral Sclerosis / mortality
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Amyotrophic Lateral Sclerosis / pathology
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Analysis of Variance
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Animals
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Astrocytes / drug effects
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Astrocytes / pathology
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Body Weight / drug effects
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Body Weight / physiology
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Delayed-Action Preparations / pharmacology
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Disease Models, Animal
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Female
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Glial Fibrillary Acidic Protein / analysis
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Humans
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Immunohistochemistry
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Injections, Spinal / methods
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Injections, Subcutaneous / methods
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Interleukin-6 / administration & dosage
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Interleukin-6 / pharmacology*
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Knee Joint / surgery
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Leukemia Inhibitory Factor
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Ligation / methods
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Male
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Mice
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Mice, Transgenic / genetics
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Motor Activity / drug effects
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Motor Activity / physiology
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Motor Neurons / drug effects
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Motor Neurons / pathology
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Neurodegenerative Diseases / drug therapy
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Neurodegenerative Diseases / pathology
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Paralysis / pathology
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Pelvis / surgery
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Recombinant Proteins / administration & dosage
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Recombinant Proteins / pharmacology
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Spinal Cord / chemistry
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Spinal Cord / drug effects
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Spinal Cord / pathology
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Superoxide Dismutase / genetics*
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Survival Rate
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Time Factors
Substances
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Delayed-Action Preparations
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Glial Fibrillary Acidic Protein
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Interleukin-6
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LIF protein, human
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Leukemia Inhibitory Factor
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Lif protein, mouse
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Recombinant Proteins
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SOD1 G93A protein
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Superoxide Dismutase