Neurotrophic growth factors for the treatment of amyotrophic lateral sclerosis: Where do we stand?

Frontiers in Neuroscience

Volumn 4, Issue JUN, 2010, Pages

  Henriques, Alexandre ^a,b,c   Pitzer, Claudia ^a   Schneider, Armin ^a  

^a SYGNIS Bioscience   (Germany)

^b UNIVERSITÉ DE STRASBOURG   (France)

^c INSERM   (France)

Author keywords

Amyotrophic lateral sclerosis; Animal model; Clinical trial; Growth factors; Motoneurons; Therapy

Indexed keywords

EID: 78649723621     PISSN: 16624548     EISSN: 1662453X     Source Type: Journal    
DOI: 10.3389/fnins.2010.00032     Document Type: Review

References (201)

1. Acsadi, G., Anguelov, R. A., Yang, H., Toth, G., Thomas, R., Jani, A., Wang, Y., Ianakova, E., Mohammad, S., Lewis, R. A., and Shy, M. E. (2002). Increased survival and function of SOD1 mice after glial cell-derived neurotrophic factor gene therapy. Hum. Gene Ther. 13, 1047-1059.
2. Aggarwal, S. P., Zinman, L., Simpson, E., McKinley, J., Jackson, K. E., Pinto, H., Kaufman, P., Conwit, R. A., Schoenfeld, D., Shefner, J., and Cudkowicz, M. (2010). Safety and efficacy of lithium in combination with riluzole for treatment of amyotrophic lateral sclerosis: a randomised, double-blind, placebo-controlled trial. Lancet Neurol. 9, 481-488.
3. ALS CNTF Treatment Study Group (1996). A double-blind placebo-controlled clinical trial of subcutaneous recombinant human ciliary neurotrophic factor (rHCNTF) in amyotrophic lateral sclerosis. Neurology 46, 1244-1249.
4. Apel, P. J., Ma, J., Callahan, M., Northam, C. N., Alton, T. B., Sonntag, W. E., and Li, Z. (2009). Effect of locally delivered IGF-1 on nerve regeneration during aging: an experimental study in rats. Muscle Nerve. 41, 335-341.
5. Arakawa, Y., Sendtner, M., and Thoenen, H. (1990). Survival effect of ciliary neurotrophic factor (CNTF) on chick embryonic motoneurons in culture: comparison with other neurotrophic factors and cytokines. J. Neurosci. 10, 3507-3515.
6. Azzouz, M., Ralph, G. S., Storkebaum, E., Walmsley, L. E., Mitrophanous, K. A., Kingsman, S. M., Carmeliet, P., and Mazarakis, N. D. (2004). VEGF delivery with retrogradely transported lentivector prolongs survival in a mouse ALS model. Nature 429, 413-417.
7. Bacman, S. R., Bradley, W. G., and Moraes, C. T. (2006). Mitochondrial involvement in amyotrophic lateral sclerosis: trigger or target? Mol. Neurobiol. 33, 113-131.
8. Barde, Y. A., Edgar, D., and Thoenen, H. (1982). Purification of a new neurotrophic factor from mammalian brain. EMBO J. 1, 549-553.
9. Beck, M., Flachenecker, P., Magnus, T., Giess, R., Reiners, K., Toyka, K. V., and Naumann, M. (2005). Autonomic dysfunction in ALS: a preliminary study on the effects of intrathecal BDNF. Amyotroph. Lateral Scler. Other Motor Neuron Disord. 6, 100-103.
10. Beers, D. R., Henkel, J. S., Zhao, W., Wang, J., and Appel, S. H. (2008). CD4+ T cells support glial neuroprotection, slow disease progression, and modify glial morphology in an animal model of inherited ALS. Proc. Natl. Acad. Sci. U.S.A. 105, 15558-15563.
11. Bemelmans, A. P., Husson, I., Jaquet, M., Mallet, J., Kosofsky, B. E., and Gressens, P. (2006). Lentiviral-mediated gene transfer of brain-derived neurotrophic factor is neuroprotective in a mouse model of neonatal excitotoxic challenge. J. Neurosci. Res. 83, 50-60.
12. Bilak, M. M., Corse, A. M., and Kuncl, R. W. (2001). Additivity and potentiation of IGF-I and GDNF in the complete rescue of postnatal motor neurons. Amyotroph. Lateral Scler. Other Motor Neuron Disord. 2, 83-91.
13. Bjorklund, T., and Kordower, J. H. (2010). Gene therapy for Parkinson's disease. Mov. Disord. 25(Suppl. 1), S161-S173.
14. Blackburn, D., Sargsyan, S., Monk, P. N., and Shaw, P. J. (2009). Astrocyte function and role in motor neuron disease: a future therapeutic target? Glia 57, 1251-1264.
15. Bogaert, E., Van Damme, P., Poesen, K., Dhondt, J., Hersmus, N., Kiraly, D., Scheveneels, W., Robberecht, W., and Van Den Bosch, L. (2009). VEGF protects motor neurons against excitotoxicity by upregulation of GluR2. Neurobiol. Aging. (in press).
16. Borasio, G. D., Robberecht, W., Leigh, P. N., Emile, J., Guiloff, R. J., Jerusalem, F., Silani, V., Vos, P. E., Wokke, J. H., and Dobbins, T. (1998). A placebo-controlled trial of insulin-like growth factor-I in amyotrophic lateral sclerosis. European ALS/IGF-I Study Group. Neurology 51, 583-586.
17. Bryan, W. W., Hoagland, R. J., Murphy, J., Armon, C., Barohn, R. J., Goodpasture, J. C., Miller, R. G., Parry, G. J., Petajan, J. H., Ross, M. A., and Stromatt, S. C. (2003). Can we eliminate placebo in ALS clinical trials? Amyotroph Lateral Scler. Other Motor Neuron Disord. 4, 11-15.
18. Buj-Bello, A., Buchman, V. L., Horton, A., Rosenthal, A., and Davies, A. M. (1995). GDNF is an age-specific survival factor for sensory and autonomic neurons. Neuron 15, 821-828.
19. Caraganis, A., Benn, S., Cudkowicz, M., and Brown, R. H. Jr. (2008). Thrombopoietin is ineffective in a mouse model of motor neuron disease. Amyotroph. Lateral Scler. Other Motor Neuron Disord. 9, 354-358.
20. Caroni, P. (1993). Activity-sensitive signaling by muscle-derived insulin-like growth factors in the developing and regenerating neuromuscular system. Ann. N. Y. Acad. Sci. 692, 209-222.
21. Carri, M. T. (2008). Minocycline for patients with ALS. Lancet Neurol. 7, 118-119; author reply 120-111.
22. Carter, B. J., Anklesaria, P., Choi, S., and Engelhardt, J. F. (2009). Redox modifier genes and pathways in amyotrophic lateral sclerosis. Antioxid. Redox Signal. 11, 1569-1586.
23. Cashman, N., Tan, L. Y., Krieger, C., Madler, B., Mackay, A., Mackenzie, I., Benny, B., Nantel, S., Fabros, M., Shinobu, L., Yousefi, M., and Eisen, A. (2008). Pilot study of granulocyte colony stimulating factor (G-CSF)-mobilized peripheral blood stem cells in amyotrophic lateral sclerosis (ALS). Muscle Nerve 37, 620-625.
24. Cassina, P., Pehar, M., Vargas, M. R., Castellanos, R., Barbeito, A. G., Estevez, A. G., Thompson, J. A., Beckman, J. S., and Barbeito, L. (2005). Astrocyte activation by fibroblast growth factor-1 and motor neuron apoptosis: implications for amyotrophic lateral sclerosis. J. Neurochem. 93, 38-46.
25. Cattaneo, E., and McKay, R. (1990). Proliferation and differentiation of neuronal stem cells regulated by nerve growth factor. Nature 347, 762-765.
26. Chen, W., Saeed, M., Mao, H., Siddique, N., Dellefave, L., Hung, W. Y., Deng, H. X., Sufit, R. L., Heller, S. L., Haines, J. L., Pericak-Vance, M., and Siddique, T. (2006). Lack of association of VEGF promoter polymorphisms with sporadic ALS. Neurology 67, 508-510.
27. Cheung, Y. K., Gordon, P. H., and Levin, B. (2006). Selecting promising ALS therapies in clinical trials. Neurology 67, 1748-1751.
28. Cohen, S., and Levi-Montalcini, R. (1957). Purification and properties of a nerve growth-promoting factor isolated from mouse sarcoma 180. Cancer Res. 17, 15-20.
29. Collard, J. F., Cote, F., and Julien, J. P. (1995). Defective axonal transport in a transgenic mouse model of amyotrophic lateral sclerosis. Nature 375, 61-64.
30. Connolly, D. T., Heuvelman, D. M., Nelson, R., Olander, J. V., Eppley, B. L., Delfino, J. J., Siegel, N. R., Leimgruber, R. M., and Feder, J. (1989). Tumor vascular permeability factor stimulates endothelial cell growth and angiogenesis. J. Clin. Invest. 84, 1470-1478.
31. Corbo, M., Lunetta, C., Magni, P., Dozio, E., Ruscica, M., Adobbati, L., and Silani, V. (2010). Free insulin-like growth factor (IGF)-1 and IGF-binding proteins-2 and -3 in serum and cerebrospinal fluid of amyotrophic lateral sclerosis patients. Eur. J. Neurol. 17, 398-404.
32. Corona, J. C., Tovar-y-Romo, L. B., and Tapia, R. (2007). Glutamate excitotoxicity and therapeutic targets for amyotrophic lateral sclerosis. Expert Opin. Ther. Targets 11, 1415-1428.
33. Couzin, J. (2007). Clinical research. ALS trial raises questions about promising drug. Science 318, 1227.
34. Cuevas, P., Carceller, F., and Gimenez-Gallego, G. (1995). Acidic fibroblast growth factor prevents post-axotomy neuronal death of the newborn rat facial nerve. Neurosci. Lett. 197, 183-186.
35. Czaplinski, A., Haverkamp, L. J., Yen, A. A., Simpson, E. P., Lai, E. C., and Appel, S. H. (2006). The value of database controls in pilot or futility studies in ALS. Neurology 67, 1827-1832.
36. Deda, H., Inci, M. C., Kurekci, A. E., Sav, A., Kayihan, K., Ozgun, E., Ustunsoy, G. E., and Kocabay, S. (2009). Treatment of amyotrophic lateral sclerosis patients by autologous bone marrow-derived hematopoietic stem cell transplantation: a 1-year follow-up. Cytotherapy 11, 18-25.
37. Devos, D., Moreau, C., Lassalle, P., Perez, T., De Seze, J., Brunaud-Danel, V., Destee, A., Tonnel, A. B., and Just, N. (2004). Low levels of the vascular endothelial growth factor in CSF from early ALS patients. Neurology 62, 2127-2129.
38. Dobrogowska, D. H., Lossinsky, A. S., Tarnawski, M., and Vorbrodt, A. W. (1998). Increased blood-brain barrier permeability and endothelial abnormalities induced by vascular endothelial growth factor. J. Neurocytol. 27, 163-173.
39. Dobrowolny, G., Giacinti, C., Pelosi, L., Nicoletti, C., Winn, N., Barberi, L., Molinaro, M., Rosenthal, N., and Musaro, A. (2005). Muscle expression of a local Igf-1 isoform protects motor neurons in an ALS mouse model. J. Cell Biol. 168, 193-199.
40. Dodge, J. C., Haidet, A. M., Yang, W., Passini, M. A., Hester, M., Clarke, J., Roskelley, E. M., Treleaven, C. M., Rizo, L., Martin, H., Kim, S. H., Kaspar, R., Taksir, T. V., Griffiths, D. A., Cheng, S. H., Shihabuddin, L. S., and Kaspar, B. K. (2008). Delivery of AAV-IGF-1 to the CNS extends survival in ALS mice through modification of aberrant glial cell activity. Mol. Ther. 16, 1056-1064.
41. Dreibelbis, J. E., Brown, R. H. Jr., Pastuszak, K. A., Smith, E. R., Kaplan, P. L., and Cudkowicz, M. E. (2002). Disease course unaltered by a single intracisternal injection of BMP-7 in ALS mice. Muscle Nerve 25, 122-123.
42. Dunckley, T., Huentelman, M. J., Craig, D. W., Pearson, J. V., Szelinger, S., Joshipura, K., Halperin, R. F., Stamper, C., Jensen, K. R., Letizia, D., Hesterlee, S. E., Pestronk, A., Levine, T., Bertorini, T., Graves, M. C., Mozaffar, T., Jackson, C. E., Bosch, P., McVey, A., Dick, A., Barohn, R., Lomen-Hoerth, C., Rosenfeld, J., O'Connor D, T., Zhang, K., Crook, R., Ryberg, H., Hutton, M., Katz, J., Simpson, E. P., Mitsumoto, H., Bowser, R., Miller, R. G., Appel, S. H., and Stephan, D. A. (2007). Whole-genome analysis of sporadic amyotrophic lateral sclerosis. N. Engl. J. Med. 357, 775-788.
43. Dupuis, L., Corcia, P., Fergani, A.,X Gonzalez De Aguilar, J. L., Bonnefont-Rousselot, D., Bittar, R., Seilhean, D., Hauw, J. J., Lacomblez, L., Loeffler, J. P., and Meininger, V. (2008a). Dyslipidemia is a protective factor in amyotrophic lateral sclerosis. Neurology 70, 1004-1009.
44. Dupuis, L., Pehar, M., Cassina, P., Rene, F., Castellanos, R., Rouaux, C., Gandelman, M., Dimou, L., Schwab, M. E., Loeffler, J. P., Barbeito, L., and Gonzalez de Aguilar, J. L. (2008b). Nogo receptor antagonizes p75NTR-dependent motor neuron death. Proc. Natl. Acad. Sci. U.S.A. 105, 740-745.
45. Dupuis, L., Gonzalez de Aguilar, J. L., Oudart, H., de Tapia, M., Barbeito, L., and Loeffler, J. P. (2004). Mitochondria in amyotrophic lateral sclerosis: a trigger and a target. Neurodegener. Dis. 1, 245-254.
46. Ebendal, T., Bengtsson, H., and Soderstrom, S. (1998). Bone morphogenetic proteins and their receptors: potential functions in the brain. J. Neurosci. Res. 51, 139-146.
47. Ebens, A., Brose, K., Leonardo, E. D., Hanson, M. G. Jr., Bladt, F., Birchmeier, C., Barres, B. A., and Tessier-Lavigne, M. (1996). Hepatocyte growth factor/scatter factor is an axonal chemoattractant and a neurotrophic factor for spinal motor neurons. Neuron 17, 1157-1172.
48. Ehrenreich, H., Hasselblatt, M., Knerlich, F., von Ahsen, N., Jacob, S., Sperling, S., Woldt, H., Vehmeyer, K., Nave, K. A., and Siren, A. L. (2005). A hematopoietic growth factor, thrombopoietin, has a proapoptotic role in the brain. Proc. Natl. Acad. Sci. U.S.A. 102, 862-867.
49. Ehrenreich, H., Timner, W., and Siren, A. L. (2004). A novel role for an established player: anemia drug erythropoietin for the treatment of cerebral hypoxia/ischemia. Transfus. Apher. Sci. 31, 39-44.
50. Engelhardt, J. I., and Appel, S. H. (1990). IgG reactivity in the spinal cord and motor cortex in amyotrophic lateral sclerosis. Arch. Neurol. 47, 1210-1216.
51. Fernandez-Santiago, R., Sharma, M., Mueller, J. C., Gohlke, H., Illig, T., Anneser, J., Munch, C., Ludolph, A., Kamm, C., and Gasser, T. (2006). Possible gender-dependent association of vascular endothelial growth factor (VEGF) gene and ALS. Neurology 66, 1929-1931.
52. Fischer, L. R., Culver, D. G., Tennant, P., Davis, A. A., Wang, M., Castellano-Sanchez, A., Khan, J., Polak, M. A., and Glass, J. D. (2004). Amyotrophic lateral sclerosis is a distal axonopathy: evidence in mice and man. Exp. Neurol. 185, 232-240.
53. Fisher, M. (2003). Recommendations for advancing development of acute stroke therapies: Stroke Therapy Academic Industry Roundtable 3. Stroke 34, 1539-1546.
54. Fisher, M., Albers, G. W., Donnan, G. A., Furlan, A. J., Grotta, J. C., Kidwell, C. S., Sacco, R. L., and Wechsler, L. R. (2005). Enhancing the development and approval of acute stroke therapies: Stroke Therapy Academic Industry roundtable. Stroke 36, 1808-1813.
55. Fisher, M., Feuerstein, G., Howells, D. W., Hurn, P. D., Kent, T. A., Savitz, S. I., and Lo, E. H. (2009). Update of the stroke therapy academic industry roundtable preclinical recommendations. Stroke 40, 2244-2250.
56. Fisher, M., Hanley, D. F., Howard, G., Jauch, E. C., and Warach, S. (2007). Recommendations from the STAIR V meeting on acute stroke trials, technology and outcomes. Stroke 38, 245-248.
57. Franz, C. K., Federici, T., Yang, J., Backus, C., Oh, S. S., Teng, Q., Carlton, E., Bishop, K. M., Gasmi, M., Bartus, R. T., Feldman, E. L., and Boulis, N. M. (2009). Intraspinal cord delivery of IGF-I mediated by adeno-associated virus 2 is neuroprotective in a rat model of familial ALS. Neurobiol. Dis. 33, 473-481.
58. Gill, S. S., Patel, N. K., Hotton, G. R., O'Sullivan, K., McCarter, R., Bunnage, M., Brooks, D. J., Svendsen, C. N., and Heywood, P. (2003). Direct brain infusion of glial cell line-derived neurotrophic factor in Parkinson disease. Nat. Med. 9, 589-595.
59. Gimenez y Ribotta, M., Revah, F., Pradier, L., Loquet, I., Mallet, J., and Privat, A. (1997). Prevention of motoneuron death by adenovirus-mediated neurotrophic factors. J. Neurosci. Res. 48, 281-285.
60. Gordon, P. H. (2009). A placebo arm is not always necessary in clinical trials of amyotrophic lateral sclerosis. Muscle Nerve 39, 858-860.
61. Gordon, P. H., Cheng, B., Montes, J., Doorish, C., Albert, S. M., and Mitsumoto, H. (2007a). Outcome measures for early phase clinical trials. Amyotroph. Lateral Scler. Other Motor Neuron Disord. 8, 270-273.
62. Gordon, P. H., Moore, D. H., Miller, R. G., Florence, J. M., Verheijde, J. L., Doorish, C., Hilton, J. F., Spitalny, G. M., MacArthur, R. B., Mitsumoto, H., Neville, H. E., Boylan, K., Mozaffar, T., Belsh, J. M., Ravits, J., Bedlack, R. S., Graves, M. C., McCluskey, L. F., Barohn, R. J., and Tandan, R. (2007b). Efficacy of minocycline in patients with amyotrophic lateral sclerosis: a phase III randomised trial. Lancet Neurol. 6, 1045-1053.
63. Gordon, P. H., Cheung, Y. K., Levin, B., Andrews, H., Doorish, C., Macarthur, R. B., Montes, J., Bednarz, K., Florence, J., Rowin, J., Boylan, K., Mozaffar, T., Tandan, R., Mitsumoto, H., Kelvin, E. A., Chapin, J., Bedlack, R., Rivner, M., McCluskey, L. F., Pestronk, A., Graves, M., Sorenson, E. J., Barohn, R. J., Belsh, J. M., Lou, J. S., Levine, T., Saperstein, D., Miller, R. G., and Scelsa, S. N. (2008). A novel, efficient, randomized selection trial comparing combinations of drug therapy for ALS. Amyotroph. Lateral Scler. Other Motor Neuron Disord. 9, 212-222.
64. Grignaschi, G., Zennaro, E., Tortarolo, M., Calvaresi, N., and Bendotti, C. (2007). Erythropoietin does not preserve motor neurons in a mouse model of familial ALS. Amyotroph. Lateral Scler. Other Motor Neuron Disord. 8, 31-35.
65. Gros-Louis, F., Laurent, S., Lopes, A. A., Khoris, J., Meininger, V., Camu, W., and Rouleau, G. A. (2003). Absence of mutations in the hypoxia response element of VEGF in ALS. Muscle Nerve 28, 774-775.
66. Grumbles, R. M., Sesodia, S., Wood, P. M., and Thomas, C. K. (2009). Neurotrophic factors improve motoneuron survival and function of muscle reinnervated by embryonic neurons. J. Neuropathol. Exp. Neurol. 68, 736-746.
67. Grundstrom, E., Lindholm, D., Johansson, A., Blennow, K., and Askmark, H. (2000). GDNF but not BDNF is increased in cerebrospinal fluid in amyotrophic lateral sclerosis. Neuroreport 11, 1781-1783.
68. Grunfeld, J. F., Barhum, Y., Blondheim, N., Rabey, J. M., Melamed, E., and Offen, D. (2007). Erythropoietin delays disease onset in an amyotrophic lateral sclerosis model. Exp. Neurol. 204, 260-263.
69. Gurney, M. E., Pu, H., Chiu, A. Y., Dal Canto, M. C., Polchow, C. Y., Alexander, D. D., Caliendo, J., Hentati, A., Kwon, Y. W., Deng, H. X., Chen, W., Zhai, P., Sufit, R. L., and Siddique, T. (1994). Motor neuron degeneration in mice that express a human Cu, Zn superoxide dismutase mutation. Science 264, 1772-1775.
70. Hedlund, E., Hefferan, M. P., Marsala, M., and Isacson, O. (2007). Cell therapy and stem cells in animal models of motor neuron disorders. Eur. J. Neurosci. 26, 1721-1737.
71. Henriques, A., Pitzer, C., Dupuis, L., and Schneider, A. (2010). G-CSF protects motoneurons against axotomy-induced apoptotic death in neonatal mice. BMC Neurosci. 11, 25.
72. Hester, M. E., Foust, K. D., Kaspar, R. W., and Kaspar, B. K. (2009). AAV as a gene transfer vector for the treatment of neurological disorders: novel treatment thoughts for ALS. Curr. Gene Ther. 9, 428-433.
73. Hobson, M. I., Green, C. J., and Terenghi, G. (2000). VEGF enhances intraneural angiogenesis and improves nerve regeneration after axotomy. J. Anat. 197, 591-605.
74. Howe, C. L., Bergstrom, R. A., and Horazdovsky, B. F. (2009). Subcutaneous IGF-1 is not beneficial in 2-year ALS trial. Neurology 73, 1247; author reply 1247-1248.
75. Huang, E. J., and Reichardt, L. F. (2003). Trk receptors: roles in neuronal signal transduction. Annu. Rev. Biochem. 72, 609-642.
76. Hwang, D. H., Lee, H. J., Park, I. H., Seok, J. I., Kim, B. G., Joo, I. S., and Kim, S. U. (2009). Intrathecal transplantation of human neural stem cells overexpressing VEGF provide behavioral improvement, disease onset delay and survival extension in transgenic ALS mice. Gene Ther. 16, 1234-1244.
77. Ikeda, K., Klinkosz, B., Greene, T., Cedarbaum, J. M., Wong, V., Lindsay, R. M., and Mitsumoto, H. (1995). Effects of brain-derived neurotrophic factor on motor dysfunction in wobbler mouse motor neuron disease. Ann. Neurol. 37, 505-511.
78. Ishigaki, A., Aoki, M., Nagai, M., Warita, H., Kato, S., Kato, M., Nakamura, T., Funakoshi, H., and Itoyama, Y. (2007). Intrathecal delivery of hepatocyte growth factor from amyotrophic lateral sclerosis onset suppresses disease progression in rat amyotrophic lateral sclerosis model. J. Neuropathol. Exp. Neurol. 66, 1037-1044.
79. Kadoyama, K., Funakoshi, H., Ohya, W., and Nakamura, T. (2007). Hepatocyte growth factor (HGF) attenuates gliosis and motoneuronal degeneration in the brainstem motor nuclei of a transgenic mouse model of ALS. Neurosci. Res. 59, 446-456.
80. Kalra, S., Genge, A., and Arnold, D. L. (2003). A prospective, randomized, placebo-controlled evaluation of corticoneuronal response to intrathecal BDNF therapy in ALS using magnetic resonance spectroscopy: feasibility and results. Amyotroph. Lateral Scler. Other Motor Neuron Disord. 4, 22-26.
81. Kaplitt, M. G., Feigin, A., Tang, C., Fitzsimons, H. L., Mattis, P., Lawlor, P. A., Bland, R. J., Young, D., Strybing, K., Eidelberg, D., and During, M. J. (2007). Safety and tolerability of gene therapy with an adeno-associated virus (AAV) borne GAD gene for Parkinson's disease: an open label, phase I trial. Lancet 369, 2097-2105.
82. Kaspar, B. K., Llado, J., Sherkat, N., Rothstein, J. D., and Gage, F. H. (2003). Retrograde viral delivery of IGF-1 prolongs survival in a mouse ALS model. Science 301, 839-842.
83. Kastin, A. J., Akerstrom, V., and Pan, W. (2003). Glial cell line-derived neurotrophic factor does not enter normal mouse brain. Neurosci. Lett. 340, 239-241.
84. Kim, H., Kim, H. Y., Choi, M. R., Hwang, S., Nam, K. H., Kim, H. C., Han, J. S., Kim, K. S., Yoon, H. S., and Kim, S. H. (2010). Dose-dependent efficacy of ALS-human mesenchymal stem cells transplantation into cisterna magna in SOD1-G93A ALS mice. Neurosci. Lett. 468, 190-194.
85. Kinoshita, Y., Ito, H., Hirano, A., Fujita, K., Wate, R., Nakamura, M., Kaneko, S., Nakano, S., and Kusaka, H. (2009). Nuclear contour irregularity and abnormal transporter protein distribution in anterior horn cells in amyotrophic lateral sclerosis. J. Neuropathol. Exp. Neurol. 68, 1184-1192.
86. Kirkeby, A., Torup, L., Bochsen, L., Kjalke, M., Abel, K., Theilgaard-Monch, K., Johansson, P. I., Bjorn, S. E., Gerwien, J., and Leist, M. (2008). High-dose erythropoietin alters platelet reactivity and bleeding time in rodents in contrast to the neuroprotective variant carbamyl-erythropoietin (CEPO). Thromb. Haemost. 99, 720-728.
87. Klimaschewski, L., Meisinger, C., and Grothe, C. (1999). Localization and regulation of basic fibroblast growth factor (FGF-2) and FGF receptor-1 in rat superior cervical ganglion after axotomy. J. Neurobiol. 38, 499-506.
88. Koh, S. H., Kim, Y., Kim, H. Y., Cho, G. W., Kim, K. S., and Kim, S. H. (2007). Recombinant human erythropoietin suppresses symptom onset and progression of G93A-SOD1 mouse model of ALS by preventing motor neuron death and inflammation. Eur. J. Neurosci. 25, 1923-1930.
89. Kosai, K., Matsumoto, K., Funakoshi, H., and Nakamura, T. (1999). Hepatocyte growth factor prevents endotoxin-induced lethal hepatic failure in mice. Hepatology 30, 151-159.
90. Kosuge, Y., Sekikawa-Nishida, K., Negi, H., Ishige, K., and Ito, Y. (2009). Characterization of chronic glutamate-mediated motor neuron toxicity in organotypic spinal cord culture prepared from ALS model mice. Neurosci. Lett. 454, 165-169.
91. Kriz, J., Nguyen, M. D., and Julien, J. P. (2002). Minocycline slows disease progression in a mouse model of amyotrophic lateral sclerosis. Neurobiol. Dis. 10, 268-278.
92. Kuipers, S. D., and Bramham, C. R. (2006). Brain-derived neurotrophic factor mechanisms and function in adult synaptic plasticity: new insights and implications for therapy. Curr. Opin. Drug Discov. Dev. 9, 580-586.
93. Lai, E. C., Felice, K. J., Festoff, B. W., Gawel, M. J., Gelinas, D. F., Kratz, R., Murphy, M. F., Natter, H. M., Norris, F. H., and Rudnicki, S. A. (1997). Effect of recombinant human insulin-like growth factor-I on progression of ALS. A placebo-controlled study. The North America ALS/IGF-I Study Group. Neurology 49, 1621-1630.
94. Lamballe, F., Smeyne, R. J., and Barbacid, M. (1994). Developmental expression of trkC, the neurotrophin-3 receptor, in the mammalian nervous system. J. Neurosci. 14, 14-28.
95. Lambrechts, D., Storkebaum, E., Morimoto, M., Del-Favero, J., Desmet, F., Marklund, S. L., Wyns, S., Thijs, V., Andersson, J., van Marion, I., Al-Chalabi, A., Bornes, S., Musson, R., Hansen, V., Beckman, L., Adolfsson, R., Pall, H. S., Prats, H., Vermeire, S., Rutgeerts, P., Katayama, S., Awata, T., Leigh, N., Lang-Lazdunski, L., Dewerchin, M., Shaw, C., Moons, L., Vlietinck, R., Morrison, K. E., Robberecht, W., Van Broeckhoven, C., Collen, D., Andersen, P. M., and Carmeliet, P. (2003). VEGF is a modifier of amyotrophic lateral sclerosis in mice and humans and protects motoneurons against ischemic death. Nat. Genet. 34, 383-394.
96. Leigh, P. N., Meininger, V., Bensimon, G., Cudkowicz, M., and Robberecht, W. (2008). Minocycline for patients with ALS. Lancet Neurol. 7, 119-120; author reply 120-111.
97. Leist, M., Ghezzi, P., Grasso, G., Bianchi, R., Villa, P., Fratelli, M., Savino, C., Bianchi, M., Nielsen, J., Gerwien, J., Kallunki, P., Larsen, A. K., Helboe, L., Christensen, S., Pedersen, L. O., Nielsen, M., Torup, L., Sager, T., Sfacteria, A., Erbayraktar, S., Erbayraktar, Z., Gokmen, N., Yilmaz, O., Cerami-Hand, C., Xie, Q. W., Coleman, T., Cerami, A., and Brines, M. (2004). Derivatives of erythropoietin that are tissue protective but not erythropoietic. Science 305, 239-242.
98. Lepore, A. C., Haenggeli, C., Gasmi, M., Bishop, K. M., Bartus, R. T., Maragakis, N. J., and Rothstein, J. D. (2007). Intraparenchymal spinal cord delivery of adeno-associated virus IGF-1 is protective in the SOD1G93A model of ALS. Brain Res. 1185, 256-265.
99. Levi-Montalcini, R., and Cohen, S. (1960). Effects of the extract of the mouse submaxillary salivary glands on the sympathetic system of mammals. Ann. N. Y. Acad. Sci. 85, 324-341.
100. Levi-Montalcini, R., and Hamburger, V. (1951). Selective growth stimulating effects of mouse sarcoma on the sensory and sympathetic nervous system of the chick embryo. J. Exp. Zool. 116, 321-361.
101. Levi-Montalcini, R., Meyer, H., and Hamburger, V. (1954). In vitro experiments on the effects of mouse sarcomas 180 and 37 on the spinal and sympathetic ganglia of the chick embryo. Cancer Res. 14, 49-57.
102. Lewczuk, P., Hasselblatt, M., Kamrowski-Kruck, H., Heyer, A., Unzicker, C., Siren, A. L., and Ehrenreich, H. (2000). Survival of hippocampal neurons in culture upon hypoxia: effect of erythropoietin. Neuroreport 11, 3485-3488.
103. Li, B., Xu, W., Luo, C., Gozal, D., and Liu, R. (2003). VEGF-induced activation of the PI3-K/Akt pathway reduces mutant SOD1-mediated motor neuron cell death. Brain Res. 111, 155-164.
104. Li, L., Oppenheim, R. W., Lei, M., and Houenou, L. J. (1994). Neurotrophic agents prevent motoneuron death following sciatic nerve section in the neonatal mouse. J. Neurobiol. 25, 759-766.
105. Li, W., Brakefield, D., Pan, Y., Hunter, D., Myckatyn, T. M., and Parsadanian, A. (2007). Muscle-derived but not centrally derived transgene GDNF is neuroprotective in G93A-SOD1 mouse model of ALS. Exp. Neurol. 203, 457-471.
106. Lin, L. F., Doherty, D. H., Lile, J. D., Bektesh, S., and Collins, F. (1993). GDNF: a glial cell line-derived neurotrophic factor for midbrain dopaminergic neurons. Science 260, 1130-1132.
107. Lin, L. F., Mismer, D., Lile, J. D., Armes, L. G., Butler, E. T. III, Vannice, J. L., and Collins, F. (1989). Purification, cloning, and expression of ciliary neurotrophic factor (CNTF). Science 246, 1023-1025.
108. Lo, D. C. (1998). Instructive roles of neurotrophins in synaptic plasticity. Prog. Brain Res. 117, 65-70.
109. Lowry, K. S., Murray, S. S., McLean, C. A., Talman, P., Mathers, S., Lopes, E. C., and Cheema, S. S. (2001). A potential role for the p75 low-affinity neurotrophin receptor in spinal motor neuron degeneration in murine and human amyotrophic lateral sclerosis. Amyotroph. Lateral Scler. Other Motor Neuron Disord. 2, 127-134.
110. Lunn, J. S., Sakowski, S. A., Kim, B., Rosenberg, A. A., and Feldman, E. L. (2009). Vascular endothelial growth factor prevents G93A-SOD1-induced motor neuron degeneration. Dev. Neurobiol. 69, 871-884.
111. Madhavan, R., and Peng, H. B. (2006). HGF induction of postsynaptic specializations at the neuromuscular junction. J. Neurobiol. 66, 134-147.
112. Manev, H., and Manev, R. (2009). Interactions with GluR1 AMPA receptors could influence the therapeutic usefulness of minocycline in ALS. Amyotroph. Lateral Scler. Other Motor Neuron Disord. 1-2.
113. Martin, L. J. (2006). Mitochondriopathy in Parkinson disease and amyotrophic lateral sclerosis. J. Neuropathol. Exp. Neurol. 65, 1103-1110.
114. Martinez, H. R., Gonzalez-Garza, M. T., Moreno-Cuevas, J. E., Caro, E., Gutierrez-Jimenez, E., and Segura, J. J. (2009). Stem-cell transplantation into the frontal motor cortex in amyotrophic lateral sclerosis patients. Cytotherapy 11, 26-34.
115. Masu, Y., Wolf, E., Holtmann, B., Sendtner, M., Brem, G., and Thoenen, H. (1993). Disruption of the CNTF gene results in motor neuron degeneration. Nature 365, 27-32.
116. Mazzini, L., Ferrero, I., Luparello, V., Rustichelli, D., Gunetti, M., Mareschi, K., Testa, L., Stecco, A., Tarletti, R., Miglioretti, M., Fava, E., Nasuelli, N., Cisari, C., Massara, M., Vercelli, R., Oggioni, G. D., Carriero, A., Cantello, R., Monaco, F., and Fagioli, F. (2009). Mesenchymal stem cell transplantation in amyotrophic lateral sclerosis: a Phase I clinical trial. Exp. Neurol. 223, 229-237.
117. Mennini, T., De Paola, M., Bigini, P., Mastrotto, C., Fumagalli, E., Barbera, S., Mengozzi, M., Viviani, B., Corsini, E., Marinovich, M., Torup, L., Van Beek, J., Leist, M., Brines, M., Cerami, A., and Ghezzi, P. (2006). Nonhematopoietic erythropoietin derivatives prevent motoneuron degeneration in vitro and in vivo. Mol. Med. 12, 153-160.
118. Messi, M. L., Clark, H. M., Prevette, D. M., Oppenheim, R. W., and Delbono, O. (2007). The lack of effect of specific overexpression of IGF-1 in the central nervous system or skeletal muscle on pathophysiology in the G93A SOD-1 mouse model of ALS. Exp. Neurol. 207, 52-63.
119. Milane, A., Tortolano, L., Fernandez, C., Bensimon, G., Meininger, V., and Farinotti, R. (2009). Brain and plasma riluzole pharmacokinetics: effect of minocycline combination. J. Pharm. Pharm. Sci. 12, 209-217.
120. Miller, R. G., Mitchell, J. D., Lyon, M., and Moore, D. H. (2007). Riluzole for amyotrophic lateral sclerosis (ALS)/motor neuron disease (MND). Cochrane Database Syst. Rev. CD001447.
121. Miller, R. G., Petajan, J. H., Bryan, W. W., Armon, C., Barohn, R. J., Goodpasture, J. C., Hoagland, R. J., Parry, G. J., Ross, M. A., and Stromatt, S. C. (1996). A placebo-controlled trial of recombinant human ciliary neurotrophic (rhCNTF) factor in amyotrophic lateral sclerosis. rhCNTF ALS Study Group. Ann. Neurol. 39, 256-260.
122. Mitchell, J. D., and Borasio, G. D. (2007). Amyotrophic lateral sclerosis. Lancet 369, 2031-2041.
123. Mitsuma, N., Yamamoto, M., Li, M., Ito, Y., Mitsuma, T., Mutoh, T., Takahashi, M., and Sobue, G. (1999). Expression of GDNF receptor (RET and GDNFR-alpha) mRNAs in the spinal cord of patients with amyotrophic lateral sclerosis. Brain Res. 820, 77-85.
124. Mohajeri, M. H., Figlewicz, D. A., and Bohn, M. C. (1999). Intramuscular grafts of myoblasts genetically modified to secrete glial cell line-derived neurotrophic factor prevent motoneuron loss and disease progression in a mouse model of familial amyotrophic lateral sclerosis. Hum. Gene Ther. 10, 1853-1866.
125. Moore, D. H., II, and Miller, R. G. (2004). Improving efficiency of ALS clinical trials using lead-in designs. Amyotroph. Lateral Scler. Other Motor Neuron Disord. 5(SUPPL. 1), 57-60.
126. Morstyn, G., Campbell, L., Souza, L. M., Alton, N. K., Keech, J., Green, M., Sheridan, W., Metcalf, D., and Fox, R. (1988). Effect of granulocyte colony stimulating factor on neutropenia induced by cytotoxic chemotherapy. Lancet 1, 667-672.
127. Nagai, M., Re, D. B., Nagata, T., Chalazonitis, A., Jessell, T. M., Wichterle, H., and Przedborski, S. (2007). Astrocytes expressing ALS-linked mutated SOD1 release factors selectively toxic to motor neurons. Nat. Neurosci. 10, 615-622.
128. Nagano, I., Ilieva, H., Shiote, M., Murakami, T., Yokoyama, M., Shoji, M., and Abe, K. (2005a). Therapeutic benefit of intrathecal injection of insulin-like growth factor-1 in a mouse model of Amyotrophic Lateral Sclerosis. J. Neurol. Sci. 235, 61-68.
129. Nagano, I., Shiote, M., Murakami, T., Kamada, H., Hamakawa, Y., Matsubara, E., Yokoyama, M., Moritaz, K., Shoji, M., and Abe, K. (2005b). Beneficial effects of intrathecal IGF-1 administration in patients with amyotrophic lateral sclerosis. Neurol. Res. 27, 768-772.
130. Nakamura, T., Nawa, K., and Ichihara, A. (1984). Partial purification and characterization of hepatocyte growth factor from serum of hepatectomized rats. Biochem. Biophys. Res. Commun. 122, 1450-1459.
131. Nakao, N., Odin, P., Lindvall, O., and Brundin, P. (1996). Differential trophic effects of basic fibroblast growth factor, insulin-like growth factor-1, and neurotrophin-3 on striatal neurons in culture. Exp. Neurol. 138, 144-157.
132. Nefussy, B., Artamonov, I., Deutsch, V., Naparstek, E., Nagler, A., and Drory, V. E. (2009). Recombinant human granulocyte-colony stimulating factor administration for treating amyotrophic lateral sclerosis: A pilot study. Amyotroph. Lateral Scler. Other Motor Neuron Disord. 1-7.
133. Ochs, G., Penn, R. D., York, M., Giess, R., Beck, M., Tonn, J., Haigh, J., Malta, E., Traub, M., Sendtner, M., and Toyka, K. V. (2000). A phase I/II trial of recombinant methionyl human brain derived neurotrophic factor administered by intrathecal infusion to patients with amyotrophic lateral sclerosis. Amyotroph. Lateral Scler. Other Motor Neuron Disord. 1, 201-206.
134. Okura, Y., Arimoto, H., Tanuma, N., Matsumoto, K., Nakamura, T., Yamashima, T., Miyazawa, T., and Matsumoto, Y. (1999). Analysis of neurotrophic effects of hepatocyte growth factor in the adult hypoglossal nerve axotomy model. Eur. J. Neurosci. 11, 4139-4144.
135. Oosthuyse, B., Moons, L., Storkebaum, E., Beck, H., Nuyens, D., Brusselmans, K., Van Dorpe, J., Hellings, P., Gorselink, M., Heymans, S., Theilmeier, G., Dewerchin, M., Laudenbach, V., Vermylen, P., Raat, H., Acker, T., Vleminckx, V., Van Den Bosch, L., Cashman, N., Fujisawa, H., Drost, M. R., Sciot, R., Bruyninckx, F., Hicklin, D. J., Ince, C., Gressens, P., Lupu, F., Plate, K. H., Robberecht, W., Herbert, J. M., Collen, D., and Carmeliet, P. (2001). Deletion of the hypoxia-response element in the vascular endothelial growth factor promoter causes motor neuron degeneration. Nat. Genet. 28, 131-138.
136. Palesch, Y. Y., and Tilley, B. C. (2004). An efficient multi-stage, single-arm Phase II futility design for ALS. Amyotroph. Lateral Scler. Other Motor Neuron Disord. 5(Suppl. 1), 55-56.
137. Pan, H. C., Wu, H. T., Cheng, F. C., Chen, C. H., Sheu, M. L., and Chen, C. J. (2009). Potentiation of angiogenesis and regeneration by G-CSF after sciatic nerve crush injury. Biochem. Biophys. Res. Commun. 382, 177-182.
138. Pan, W., Banks, W. A., Fasold, M. B., Bluth, J., and Kastin, A. J. (1998). Transport of brain-derived neurotrophic factor across the blood-brain barrier. Neuropharmacology 37, 1553-1561.
139. Pan, W., Kastin, A. J., Maness, L. M., and Brennan, J. M. (1999). Saturable entry of ciliary neurotrophic factor into brain. Neurosci. Lett. 263, 69-71.
140. Pardridge, W. M., Kang, Y. S., and Buciak, J. L. (1994). Transport of human recombinant brain-derived neurotrophic factor (BDNF) through the rat blood-brain barrier in vivo using vector-mediated peptide drug delivery. Pharm. Res. 11, 738-746.
141. Park, S., Kim, H. T., Yun, S., Kim, I. S., Lee, J., Lee, I. S., and Park, K. I. (2009). Growth factor-expressing human neural progenitor cell grafts protect motor neurons but do not ameliorate motor performance and survival in ALS mice. Exp. Mol. Med. 41, 487-500.
142. Pasinelli, P., and Brown, R. H. (2006). Molecular biology of amyotrophic lateral sclerosis: insights from genetics. Nat. Rev. Neurosci. 7, 710-723.
143. Patel, N. K., Bunnage, M., Plaha, P., Svendsen, C. N., Heywood, P., and Gill, S. S. (2005). Intraputamenal infusion of glial cell line-derived neurotrophic factor in PD: a two-year outcome study. Ann. Neurol. 57, 298-302.
144. Piehl, F., Ji, R. R., Cullheim, S., Hokfelt, T., Lindholm, D., and Hughes, R. A. (1995). Fibroblast growth factors regulate calcitonin gene-related peptide mRNA expression in rat motoneurons after lesion and in culture. Eur. J. Neurosci. 7, 1739-1750.
145. Pitzer, C., Klussmann, S., Kruger, C., Letellier, E., Plaas, C., Dittgen, T., Kirsch, F., Stieltjes, B., Weber, D., Laage, R., Martin-Villalba, A., and Schneider, A. (2010). The hematopoietic factor granulocyte-colony stimulating factor improves outcome in experimental spinal cord injury. J. Neurochem. 113, 930-942.
146. Pitzer, C., Kruger, C., Plaas, C., Kirsch, F., Dittgen, T., Muller, R., Laage, R., Kastner, S., Suess, S., Spoelgen, R., Henriques, A., Ehrenreich, H., Schabitz, W. R., Bach, A., and Schneider, A. (2008). Granulocyte-colony stimulating factor improves outcome in a mouse model of amyotrophic lateral sclerosis. Brain 131, 3335-3347.
147. Poduslo, J. F., and Curran, G. L. (1996). Permeability at the blood-brain and blood-nerve barriers of the neurotrophic factors: NGF, CNTF, NT-3, BDNF. Brain Res. 36, 280-286.
148. Ratnaparkhi, A., Lawless, G. M., Schweizer, F. E., Golshani, P., and Jackson, G. R. (2008). A Drosophila model of ALS: human ALS-associated mutation in VAP33A suggests a dominant negative mechanism. PLoS ONE 3, e2334. doi:10.1371/journal.pone.0002334.
149. Rothstein, J. D. (2009). Current hypotheses for the underlying biology of amyotrophic lateral sclerosis. Ann. Neurol. 65(Suppl 1), S3-S9.
150. Samoylenko, A., Byts, N., Rajalingam, K., von Ahsen, N., Rapp, U. R., Ehrenreich, H., and Siren, A. L. (2008). Thrombopoietin inhibits nerve growth factor-induced neuronal differentiation and ERK signalling. Cell. Signal. 20, 154-162.
151. Saver, J. L., Albers, G. W., Dunn, B., Johnston, K. C., and Fisher, M. (2009). Stroke Therapy Academic Industry Roundtable (STAIR) recommendations for extended window acute stroke therapy trials. Stroke 40, 2594-2600.
152. Schiffer, D., Cordera, S., Cavalla, P., and Migheli, A. (1996). Reactive astrogliosis of the spinal cord in amyotrophic lateral sclerosis. J. Neurol. Sci. 139(SUPPL.), 27-33.
153. Schneider, A., Kruger, C., Steigleder, T., Weber, D., Pitzer, C., Laage, R., Aronowski, J., Maurer, M. H., Gassler, N., Mier, W., Hasselblatt, M., Kollmar, R., Schwab, S., Sommer, C., Bach, A., Kuhn, H. G., and Schabitz, W. R. (2005). The hematopoietic factor G-CSF is a neuronal ligand that counteracts programmed cell death and drives neurogenesis. J. Clin. Invest. 115, 2083-2098.
154. Schoenfeld, D. A., and Cudkowicz, M. (2008). Design of phase II ALS clinical trials. Amyotroph. Lateral Scler. Other Motor Neuron Disord. 9, 16-23.
155. Schymick, J. C., Talbot, K., and Traynor, B. J. (2007). Genetics of sporadic amyotrophic lateral sclerosis. Hum. Mol. Genet. 16, R233-R242.
156. Scott, S., Kranz, J. E., Cole, J., Lincecum, J. M., Thompson, K., Kelly, N., Bostrom, A., Theodoss, J., Al-Nakhala, B. M., Vieira, F. G., Ramasubbu, J., and Heywood, J. A. (2008). Design, power, and interpretation of studies in the standard murine model of ALS. Amyotroph. Lateral Scler. Other Motor Neuron Disord. 9, 4-15.
157. Sendtner, M., Holtmann, B., Kolbeck, R., Thoenen, H., Barde, Y. A. (1992a). Brain-derived neurotrophic factor prevents the death of motoneurons in newborn rats after nerve section. Nature 360, 757-759.
158. Sendtner, M., Schmalbruch, H., Stockli, K. A., Carroll, P., Kreutzberg, G. W., and Thoenen, H. (1992b). Ciliary neurotrophic factor prevents degeneration of motor neurons in mouse mutant progressive motor neuronopathy. Nature 358, 502-504.
159. Sendtner, M., Kreutzberg, G. W., and Thoenen, H. (1990). Ciliary neurotrophic factor prevents the degeneration of motor neurons after axotomy. Nature 345, 440-441.
160. Shefner, J. M., Cudkowicz, M. E., Zhang, H., Schoenfeld, D., and Jillapalli, D. (2004). The use of statistical MUNE in a multicenter clinical trial. Muscle Nerve 30, 463-469.
161. Shemer, J., Raizada, M. K., Masters, B. A., Ota, A., and LeRoith, D. (1987). Insulin-like growth factor I receptors in neuronal and glial cells. Characterization and biological effects in primary culture. J. Biol. Chem. 262, 7693-7699.
162. Simmons, Z. (2009). Can we eliminate placebo in ALS clinical Trials? Muscle Nerve 39, 861-865.
163. Siren, A. L., Fratelli, M., Brines, M., Goemans, C., Casagrande, S., Lewczuk, P., Keenan, S., Gleiter, C., Pasquali, C., Capobianco, A., Mennini, T., Heumann, R., Cerami, A., Ehrenreich, H., and Ghezzi, P. (2001a). Erythropoietin prevents neuronal apoptosis after cerebral ischemia and metabolic stress. Proc. Natl. Acad. Sci. U.S.A. 98, 4044-4049.
164. Siren, A. L., Knerlich, F., Poser, W., Gleiter, C. H., Bruck, W., and Ehrenreich, H. (2001b). Erythropoietin and erythropoietin receptor in human ischemic/hypoxic brain. Acta Neuropathol. 101, 271-276.
165. Sondell, M., Lundborg, G., and Kanje, M. (1999). Vascular endothelial growth factor has neurotrophic activity and stimulates axonal outgrowth, enhancing cell survival and Schwann cell proliferation in the peripheral nervous system. J. Neurosci. 19, 5731-5740.
166. Sondell, M., Sundler, F., and Kanje, M. (2000). Vascular endothelial growth factor is a neurotrophic factor which stimulates axonal outgrowth through the flk-1 receptor. Eur. J. Neurosci. 12, 4243-4254.
167. Sorenson, E. J., Windbank, A. J., Mandrekar, J. N., Bamlet, W. R., Appel, S. H., Armon, C., Barkhaus, P. E., Bosch, P., Boylan, K., David, W. S., Feldman, E., Glass, J., Gutmann, L., Katz, J., King, W., Luciano, C. A., McCluskey, L. F., Nash, S., Newman, D. S., Pascuzzi, R. M., Pioro, E., Sams, L. J., Scelsa, S., Simpson, E. P., Subramony, S. H., Tiryaki, E., and Thornton, C. A. (2008). Subcutaneous IGF-1 is not beneficial in 2-year ALS trial. Neurology 71, 1770-1775.
168. Statler, P. A., McPherson, R. J., Bauer, L. A., Kellert, B. A., and Juul, S. E. (2007). Pharmacokinetics of high-dose recombinant erythropoietin in plasma and brain of neonatal rats. Pediatr. Res. 61, 671-675.
169. Storkebaum, E., Lambrechts, D., Dewerchin, M., Moreno-Murciano, M. P., Appelmans, S., Oh, H., Van Damme, P., Rutten, B., Man, W. Y., De Mol, M., Wyns, S., Manka, D., Vermeulen, K., Van Den Bosch, L., Mertens, N., Schmitz, C., Robberecht, W., Conway, E. M., Collen, D., Moons, L., and Carmeliet, P. (2005). Treatment of motoneuron degeneration by intracerebroventricular delivery of VEGF in a rat model of ALS. Nat. Neurosci. 8, 85-92.
170. Stroke Therapy Academic Industry Roundtable II (STAIR-II). (2001). Recommendations (for) clinical trial evaluation of acute stroke therapies. Stroke 32, 1598-1606.
171. Strom, A. L., Gal, J., Shi, P., Kasarskis, E. J., Hayward, L. J., and Zhu, H. (2008). Retrograde axonal transport and motor neuron disease. J. Neurochem. 106, 495-505.
172. Sun, W., Funakoshi, H., and Nakamura, T. (2002). Overexpression of HGF retards disease progression and prolongs life span in a transgenic mouse model of ALS. J. Neurosci. 22, 6537-6548.
173. Suzuki, M., McHugh, J., Tork, C., Shelley, B., Klein, S. M., Aebischer, P., and Svendsen, C. N. (2007). GDNF secreting human neural progenitor cells protect dying motor neurons, but not their projection to muscle, in a rat model of familial ALS. PLoS ONE 2, e689. doi:10.1371/journal.pone.0000689.
174. Tatsumi, R., Sankoda, Y., Anderson, J. E., Sato, Y., Mizunoya, W., Shimizu, N., Suzuki, T., Yamada, M., Rhoads, R. P., Jr., Ikeuchi, Y., and Allen, R. E. (2009). Possible implication of satellite cells in regenerative motoneuritogenesis: HGF upregulates neural chemorepellent Sema3A during myogenic differentiation. Am. J. Physiol. Cell Physiol. 297, C238-C252.
175. The BDNF Study Group (Phase III) (1999). A controlled trial of recombinant methionyl human BDNF in ALS. Neurology 52, 1427-1433.
176. Tolosa, L., Mir, M., Asensio, V. J., Olmos, G., and Llado, J. (2008). Vascular endothelial growth factor protects spinal cord motoneurons against glutamate-induced excitotoxicity via phosphatidylinositol 3-kinase. J. Neurochem. 105, 1080-1090.
177. Toth, C., Martinez, J. A., Liu, W. Q., Diggle, J., Guo, G. F., Ramji, N., Mi, R., Hoke, A., and Zochodne, D. W. (2008). Local erythropoietin signaling enhances regeneration in peripheral axons. Neuroscience 154, 767-783.
178. Tsuboi, Y., Kakimoto, K., Akatsu, H., Daikuhara, Y., and Yamada, T. (2002). Hepatocyte growth factor in cerebrospinal fluid in neurologic disease. Acta Neurol. Scand. 106, 99-103.
179. Turner, B. J., Murray, S. S., Piccenna, L. G., Lopes, E. C., Kilpatrick, T. J., and Cheema, S. S. (2004). Effect of p75 neurotrophin receptor antagonist on disease progression in transgenic amyotrophic lateral sclerosis mice. J. Neurosci. Res. 78, 193-199.
180. Tuttle, R., and O'Leary, D. D. (1998). Neurotrophins rapidly modulate growth cone response to the axon guidance molecule, collapsin-1. Mol. Cell. Neurosci. 11, 1-8.
181. Valdes-Sanchez, T., Kirstein, M., Perez-Villalba, A., Vega, J. A., and Farinas, I. (2010). BDNF is essentially required for the early postnatal survival of nociceptors. Dev. Biol. 339, 465-476.
182. Valdmanis, P. N., Daoud, H., Dion, P. A., and Rouleau, G. A. (2009). Recent advances in the genetics of amyotrophic lateral sclerosis. Curr. Neurol. Neurosci. Rep. 9, 198-205.
183. Van Den Bosch, L., Tilkin, P., Lemmens, G., and Robberecht, W. (2002). Minocycline delays disease onset and mortality in a transgenic model of ALS. Neuroreport 13, 1067-1070.
184. Van Vught, P. W., Sutedja, N. A., Veldink, J. H., Koeleman, B. P., Groeneveld, G. J., Wijmenga, C., Uitdehaag, B. M., de Jong, J. M., Baas, F., Wokke, J. H., and Van den Berg, L. H. (2005). Lack of association between VEGF polymorphisms and ALS in a Dutch population. Neurology 65, 1643-1645.
185. Vercelli, A., Mereuta, O. M., Garbossa, D., Muraca, G., Mareschi, K., Rustichelli, D., Ferrero, I., Mazzini, L., Madon, E., and Fagioli, F. (2008). Human mesenchymal stem cell transplantation extends survival, improves motor performance and decreases neuroinflammation in mouse model of amyotrophic lateral sclerosis. Neurobiol. Dis. 31, 395-405.
186. Vicario-Abejon, C., Owens, D., McKay, R., and Segal, M. (2002). Role of neurotrophins in central synapse formation and stabilization. Nat. Rev. Neurosci. 3, 965-974.
187. Vincent, A. M., Mobley, B. C., Hiller, A., and Feldman, E. L. (2004). IGF-I prevents glutamate-induced motor neuron programmed cell death. Neurobiol. Dis. 16, 407-416.
188. Wang, W., Merrill, M. J., and Borchardt, R. T. (1996). Vascular endothelial growth factor affects permeability of brain microvessel endothelial cells in vitro. Am. J. Physiol. 271, C1973-C1980.
189. Wang, Y., Mao, X. O., Xie, L., Banwait, S., Marti, H. H., Greenberg, D. A., and Jin, K. (2007). Vascular endothelial growth factor overexpression delays neurodegeneration and prolongs survival in amyotrophic lateral sclerosis mice. J. Neurosci. 27, 304-307.
190. Wilczak, N., De Vos, R. A., and De Keyser, J. (2003). Free insulin-like growth factor (IGF)-I and IGF binding proteins 2, 5, and 6 in spinal motor neurons in amyotrophic lateral sclerosis. Lancet 361, 1007-1011.
191. Wong, V., Glass, D. J., Arriaga, R., Yancopoulos, G. D., Lindsay, R. M., and Conn, G. (1997). Hepatocyte growth factor promotes motor neuron survival and synergizes with ciliary neurotrophic factor. J. Biol. Chem. 272, 5187-5191.
192. Xiao, Q., Zhao, W., Beers, D. R., Yen, A. A., Xie, W., Henkel, J. S., and Appel, S. H. (2007). Mutant SOD1(G93A) microglia are more neurotoxic relative to wild-type microglia. J. Neurochem. 102, 2008-2019.
193. Yan, Q., Elliott, J., and Snider, W. D. (1992). Brain-derived neurotrophic factor rescues spinal motor neurons from axotomy-induced cell death. Nature 360, 753-755.
194. Yang, J. P., Liu, H. J., Cheng, S. M., Wang, Z. L., Cheng, X., Yu, H. X., and Liu, X. F. (2009). Direct transport of VEGF from the nasal cavity to brain. Neurosci. Lett. 449, 108-111.
195. Yang, M., Xia, W. J., Li, K., Pong, N. H., Chik, K. W., Li, C. K., Ng, M. H., Ng, H. K., Fung, K. P., and Fok, T. F. (2004). Identification of TPO receptors on central nervous system-a preliminary report. Zhongguo Shi Yan Xue Ye Xue Za Zhi 12, 494-497.
196. Zhang, W., Narayanan, M., and Friedlander, R. M. (2003). Additive neuroprotective effects of minocycline with creatine in a mouse model of ALS. Ann. Neurol. 53, 267-270.
197. Zhang, Y., Wang, L., Fu, Y., Song, H., Zhao, H., Deng, M., Zhang, J., and Fan, D. (2008). Preliminary investigation of effect of granulocyte colony stimulating factor on amyotrophic lateral sclerosis. Amyotroph. Lateral Scler. Other Motor Neuron Disord. 1-2.
198. Zhang, Y., Zhang, H., Fu, Y., Song, H., Wang, L., Zhang, J., and Fan, D. (2006). VEGF C2578A polymorphism does not contribute to amyotrophic lateral sclerosis susceptibility in sporadic Chinese patients. Amyotroph. Lateral Scler. Other Motor Neuron Disord. 7, 119-122.
199. Zhao, L. R., Navalitloha, Y., Singhal, S., Mehta, J., Piao, C. S., Guo, W. P., Kessler, J. A., and Groothuis, D. R. (2007). Hematopoietic growth factors pass through the blood-brain barrier in intact rats. Exp. Neurol. 204, 569-573.
200. Zheng, C., Skold, M. K., Li, J., Nennesmo, I., Fadeel, B., and Henter, J. I. (2007). VEGF reduces astrogliosis and preserves neuromuscular junctions in ALS transgenic mice. Biochem. Biophys. Res. Commun. 363, 989-993.
201. Zhu, S., Stavrovskaya, I. G., Drozda, M., Kim, B. Y., Ona, V., Li, M., Sarang, S., Liu, A. S., Hartley, D. M., Wu, D. C., Gullans, S., Ferrante, R. J., Przedborski, S., Kristal, B. S., and Friedlander, R. M. (2002). Minocycline inhibits cytochrome c release and delays progression of amyotrophic lateral sclerosis in mice. Nature 417, 74-78.