The effect of leukaemia inhibitory factor on SOD1 G93A murine amyotrophic lateral sclerosis.
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.
Feeney
Sandra J
SJ
Melbourne Neuromuscular Research Institute, St. Vincent's Hospital, Fitzroy, Victoria 3065, Australia.
Austin
Lawrence
L
Bennett
Timothy M
TM
Kurek
John B
JB
Jean-Francois
M J Bernadette
MJ
Muldoon
Catriona
C
Byrne
Edward
E
D000690:Amyotrophic Lateral Sclerosis / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D000704:Analysis of Variance; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000473:pathology; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D003692:Delayed-Action Preparations / Q000494:pharmacology; D004195:Disease Models, Animal; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D007278:Injections, Spinal / Q000379:methods; D007279:Injections, Subcutaneous / Q000379:methods; D015850:Interleukin-6 / Q000008:administration & dosage / Q000494:pharmacology*; D007719:Knee Joint / Q000601:surgery; D053605:Leukemia Inhibitory Factor; D008026:Ligation / Q000379:methods; D008297:Male; D051379:Mice; D008822:Mice, Transgenic / Q000235:genetics; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009046:Motor Neurons / Q000187:drug effects / Q000473:pathology; D019636:Neurodegenerative Diseases / Q000188:drug therapy / Q000473:pathology; D010243:Paralysis / Q000473:pathology; D010388:Pelvis / Q000601:surgery; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D013116:Spinal Cord / Q000737:chemistry / Q000187:drug effects / Q000473:pathology; D013482:Superoxide Dismutase / Q000235:genetics*; D015996:Survival Rate; D013997:Time Factors
D003692:Delayed-Action Preparations; D005904:Glial Fibrillary Acidic Protein; D015850:Interleukin-6; C507837:LIF protein, human; D053605:Leukemia Inhibitory Factor; C507838:Lif protein, mouse; D011994:Recombinant Proteins; C109415:SOD1 G93A protein; D013482:Superoxide Dismutase