Metformin treatment has no beneficial effect in a dose-response survival study in the SOD1 G93A mouse model of ALS and is harmful in female mice

PLoS ONE

Volumn 6, Issue 9, 2011, Pages

  Kaneb, Hannah M ^a,b   Sharp, Paul S ^a,c   Rahmani Kondori, Nazanin ^a,b   Wells, Dominic J ^b  

^a IMPERIAL COLLEGE LONDON   (United Kingdom)

^b ROYAL VETERINARY COLLEGE   (United Kingdom)

^c UNIVERSITY OF SHEFFIELD   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

METFORMIN; SUPEROXIDE DISMUTASE;

AMYOTROPHIC LATERAL SCLEROSIS; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BODY WEIGHT; CONTROLLED STUDY; DISEASE COURSE; DOSE RESPONSE; DRUG ACTIVITY; ELECTROPHYSIOLOGY; EXTENSOR DIGITORUM LONGUS MUSCLE; FEMALE; IN VIVO STUDY; MALE; MOTOR UNIT; MOUSE; NONHUMAN; ONSET AGE; SURVIVAL RATE; TIBIALIS ANTERIOR MUSCLE; AGING; AMINO ACID SUBSTITUTION; ANIMAL; CELL COUNT; DISEASE MODEL; DRUG EFFECT; GENETICS; HUMAN; KAPLAN MEIER METHOD; MOTONEURON; PATHOLOGY; TRANSGENIC MOUSE; TREATMENT OUTCOME;

MURINAE; MUS;

AGING; AMINO ACID SUBSTITUTION; AMYOTROPHIC LATERAL SCLEROSIS; ANIMALS; BODY WEIGHT; CELL COUNT; DISEASE MODELS, ANIMAL; DISEASE PROGRESSION; DOSE-RESPONSE RELATIONSHIP, DRUG; FEMALE; HUMANS; KAPLAN-MEIER ESTIMATE; MALE; METFORMIN; MICE; MICE, TRANSGENIC; MOTOR NEURONS; SUPEROXIDE DISMUTASE; TREATMENT OUTCOME;

EID: 80052364474     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0024189     Document Type: Article

References (46)

1. Cozzolino M, Ferri A, Carri MT, (2008) Amyotrophic lateral sclerosis: from current developments in the laboratory to clinical implications. Antioxidants & redox signaling 10: 405-443.
2. Rosen DR, Siddique T, Patterson D, Figlewicz DA, Sapp P, et al. (1993) Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis. Nature 362: 59-62.
3. Papadimitriou D, Le Verche V, Jacquier A, Ikiz B, Przedborski S, et al. (2010) Inflammation in ALS and SMA: Sorting out the good from the evil. Neurobiology of disease 37: 493-502.
4. Ilieva H, Polymenidou M, Cleveland DW, (2009) Non-cell autonomous toxicity in neurodegenerative disorders: ALS and beyond. The Journal of cell biology 187: 761-772.
5. Duffy LM, Chapman AL, Shaw PJ, Grierson AJ, (2011) The role of mitochondria in the pathogenesis of Amyotrophic Lateral Sclerosis. Neuropathology and Applied Neurobiology 37: 336-352.
6. Hawley SA, Gadalla AE, Olsen GS, Hardie DG, (2002) The Antidiabetic Drug Metformin Activates the AMP-Activated Protein Kinase Cascade via an Adenine Nucleotide-Independent Mechanism. Diabetes 51: 2420-2425.
7. Zhou G, Myers R, Li Y, Chen Y, Shen X, et al. (2001) Role of AMP-activated protein kinase in mechanism of metformin action. The Journal of Clinical Investigation 108: 1167-1174.
8. Cho Y, Kieffer T, (2011) New aspects of an old drug: metformin as a glucagon-like peptide 1 (GLP-1) enhancer and sensitiser. Diabetologia 54: 219-222.
9. Dandona P, Aljada A, Ghanim H, Mohanty P, Tripathy C, et al. (2004) Increased Plasma Concentration of Macrophage Migration Inhibitory Factor (MIF) and MIF mRNA in Mononuclear Cells in the Obese and the Suppressive Action of Metformin. J Clin Endocrinol Metab 89: 5043-5047.
10. Isoda K, Young JL, Zirlik A, MacFarlane LA, Tsuboi N, et al. (2006) Metformin Inhibits Proinflammatory Responses and Nuclear Factor-{kappa}B in Human Vascular Wall Cells. Arterioscler Thromb Vasc Biol 26: 611-617.
11. Lin HZ, Yang SQ, Chuckaree C, Kuhajda F, Ronnet G, et al. (2000) Metformin reverses fatty liver disease in obese, leptin-deficient mice. Nat Med 6: 998-1003.
12. Ouslimani N, Peynet J, Bonnefont-Rousselot D, Thérond P, Legrand A, et al. (2005) Metformin decreases intracellular production of reactive oxygen species in aortic endothelial cells. Metabolism 54: 829-834.
13. Srividhya S, Ravichandran MK, Anuradha CV, (2002) Metformin attenuates blood lipid peroxidation and potentiates antioxidant defense in high fructose-fed rats. J Biochem Mol Biol Biophys 6: 379-385.
14. Kukidome D, Nishikawa T, Sonoda K, Imoto K, Fujisawa K, et al. (2006) Activation of AMP-Activated Protein Kinase Reduces Hyperglycemia-Induced Mitochondrial Reactive Oxygen Species Production and Promotes Mitochondrial Biogenesis in Human Umbilical Vein Endothelial Cells. Diabetes 55: 120-127.
15. Chen Y, Zhou K, Wang R, Liu Y, Kwak Y-D, et al. (2009) Antidiabetic drug metformin (GlucophageR) increases biogenesis of Alzheimer's amyloid peptides via up-regulating BACE1 transcription. Proceedings of the National Academy of Sciences 106: 3907-3912.
16. Ma TC, Buescher JL, Oatis B, Funk JA, Nash AJ, et al. (2007) Metformin therapy in a transgenic mouse model of Huntington's disease. Neuroscience letters 411: 98-103.
17. Beal MF, Ferrante RJ, (2004) Experimental therapeutics in transgenic mouse models of Huntington's disease. Nat Rev Neurosci 5: 373-384.
18. Stadelmann C, (2011) Multiple sclerosis as a neurodegenerative disease: pathology, mechanisms and therapeutic implications. Curr Opin Neurol.
19. Nath N, Khan M, Paintlia MK, Hoda MN, Giri S, (2009) Metformin Attenuated the Autoimmune Disease of the Central Nervous System in Animal Models of Multiple Sclerosis. The Journal of Immunology 182: 8005-8014.
20. Gurney ME, Pu H, Chiu AY, Dal Canto MC, Polchow CY, et al. (1994) Motor neuron degeneration in mice that express a human Cu,Zn superoxide dismutase mutation. Science (New York, NY) 264: 1772-1775.
21. Parkhouse WS, Cunningham L, McFee I, Miller JM, Whitney D, et al. (2008) Neuromuscular dysfunction in the mutant superoxide dismutase mouse model of amyotrophic lateral sclerosis. Amyotroph Lateral Scler 9: 24-34.
22. Scott S, Kranz JE, Cole J, Lincecum JM, Thompson K, et al. (2008) Design, power, and interpretation of studies in the standard murine model of ALS. Amyotrophic lateral sclerosis: official publication of the World Federation of Neurology Research Group on Motor Neuron Diseases 9: 4-15.
23. Sharp PS, Akbar MT, Bouri S, Senda A, Joshi K, et al. (2008) Protective effects of heat shock protein 27 in a model of ALS occur in the early stages of disease progression. Neurobiology of disease 30: 42-55.
24. Azzouz M, Ralph G, Storkebaum E, Walmsley L, Mitrophanous K, et al. (2004) VEGF delivery with retrogradely transported lentivector prolongs survival in a mouse ALS model. Nature 429: 413-417.
25. Chengyun Z, Inger N, Bengt F, Jan-Inge H, (2004) Vascular endothelial growth factor prolongs survival in a transgenic mouse model of ALS. Annals of Neurology 56: 564-567.
26. Hegedus J, Putman CT, Gordon T, (2007) Time course of preferential motor unit loss in the SOD1 G93A mouse model of amyotrophic lateral sclerosis. Neurobiology of disease 28: 154-164.
27. Alexander GM, Erwin KL, Byers N, Deitch JS, Augelli BJ, et al. (2004) Effect of transgene copy number on survival in the G93A SOD1 transgenic mouse model of ALS. Brain researchMolecular brain research 130: 7-15.
28. Sharp PS, Dick JR, Greensmith L, (2005) The effect of peripheral nerve injury on disease progression in the SOD1(G93A) mouse model of amyotrophic lateral sclerosis. Neuroscience 130: 897-910.
29. Gill A, Kidd J, Vieira F, Thompson K, Perrin S, (2009) No Benefit from Chronic Lithium Dosing in a Sibling-Matched, Gender Balanced, Investigator-Blinded Trial Using a Standard Mouse Model of Familial ALS. PLoS ONE 4: e6489.
30. Lincecum JM, Vieira FG, Wang MZ, Thompson K, De Zutter GS, et al. (2010) From transcriptome analysis to therapeutic anti-CD40L treatment in the SOD1 model of amyotrophic lateral sclerosis. Nat Genet 42: 392-399.
31. Choi C-I, Lee Y-D, Gwag BJ, Cho SI, Kim S-S, et al. (2008) Effects of estrogen on lifespan and motor functions in female hSOD1 G93A transgenic mice. Journal of the neurological sciences 268: 40-47.
32. Matthews JN, Altman DG, Campbell MJ, Royston P, (1990) Analysis of serial measurements in medical research. BMJ 300: 230-235.
33. Traynor BJ, Bruijn L, Conwit R, Beal F, O'Neill G, et al. (2006) Neuroprotective agents for clinical trials in ALS: A systematic assessment. Neurology 67: 20-27.
34. Gould TW, Buss RR, Vinsant S, Prevette D, Sun W, et al. (2006) Complete Dissociation of Motor Neuron Death from Motor Dysfunction by Bax Deletion in a Mouse Model of ALS. J Neurosci 26: 8774-8786.
35. Dadon-Nachum M, Melamed E, Offen D, (2011) The "Dying-Back" Phenomenon of Motor Neurons in ALS. Journal of Molecular Neuroscience 43: 470-477.
36. Hegedus J, Putman CT, Tyreman N, Gordon T, (2008) Preferential motor unit loss in the SOD1 G93A transgenic mouse model of amyotrophic lateral sclerosis. The Journal of physiology 586: 3337-3351.
37. Ludolph AC, Jesse S, (2009) Review: Evidence-based drug treatment in amyotrophic lateral sclerosis and upcoming clinical trials. Therapeutic Advances in Neurological Disorders 2: 319-326.
38. Ludolph AC, Bendotti C, Blaugrund E, Chio A, Greensmith L, et al. (2010) Guidelines for preclinical animal research in ALS/MND: A consensus meeting. Amyotroph Lateral Scler 11: 38-45.
39. Leitner M, Menzies S, Lutz C, (2009) Working with ALS mice: Guidelines for preclinical testing and colony management. Available:http://www.researchals.org/uploaded_files/p4l_jax_sod1manual_20091202_29aPcx.pdf.
40. Brunmair B, Staniek K, Gras F, Scharf N, Althaym A, et al. (2004) Thiazolidinediones, Like Metformin, Inhibit Respiratory Complex I. Diabetes 53: 1052-1059.
41. Ferri A, Cozzolino M, Crosio C, Nencini M, Casciati A, et al. (2006) Familial ALS-superoxide dismutases associate with mitochondria and shift their redox potentials. Proceedings of the National Academy of Sciences 103: 13860-13865.
42. Dupuis L, Corcia P, Fergani A, Gonzalez De Aguilar J-L, Bonnefont-Rousselot D, et al. (2008) Dyslipidemia is a protective factor in amyotrophic lateral sclerosis. Neurology 70: 1004-1009.
43. Groeneveld GJ, Van Muiswinkel FL, Sturkenboom JM, Wokke JHJ, Bär PR, et al. (2004) Ovariectomy and 17[beta]-estradiol modulate disease progression of a mouse model of ALS. Brain research 1021: 128-131.
44. Rice S, Pellatt L, Ramanathan K, Whitehead SA, Mason HD, (2009) Metformin Inhibits Aromatase via an Extracellular Signal-Regulated Kinase-Mediated Pathway. Endocrinology 150: 4794-4801.
45. Mansfield R, Galea R, Brincat M, Hole D, Mason H, (2003) Metformin has direct effects on human ovarian steroidogenesis. Fertility and Sterility 79: 956-962.
46. Jawaid A, Salamone AR, Strutt AM, Murthy SB, Wheaton M, et al. (2010) ALS disease onset may occur later in patients with pre-morbid diabetes mellitus. European Journal of Neurology 17: 733-739.