Therapy development for ALS: Lessons learned and path forward

References

• Andersen PM, Borasio GD, Dengler R, Hardiman O, Kollewe K, Leigh PN, et al. Good practice in the management of amyotrophic lateral sclerosis: clinical guidelines. An evidence-based review with good practice points. EALSC Working Group. Amyotrophic Lateral Sclerosis. 2007; 8: 195–213
   PubMed Web of Science ®Google Scholar
• Lechtzin N, Scott Y, Busse AM, Clawson LL, Kimball R, Wiener CM. Early use of non-invasive ventilation prolongs survival in subjects with ALS. Amyotrophic Lateral Sclerosis. 2007; 8: 185–8
   PubMed Web of Science ®Google Scholar
• Bruijn LI, Miller TM, Cleveland DW. Unraveling the mechanisms involved in motor neuron degeneration in ALS. Annual Review of Neuroscience. 2004; 27: 723
   PubMed Web of Science ®Google Scholar
• Bruijn LI, Cleveland DW. Mechanisms of selective motor neuron death in ALS: insights from transgenic mouse models of motor neuron disease. Neuropathology Applied Neurobiology. 1996; 22: 373–87
   PubMed Web of Science ®Google Scholar
• Fornai F, Longone P, Ferrucci M, Lenzi P, Isidoro C, Ruggieri S, et al Autophagy and amyotrophic lateral sclerosis: the multiple roles of lithium. Autophagy. 2008;4: (Epub ahead of print).
   PubMed Web of Science ®Google Scholar
• Lil L Zhang X Le W. Altered macroautophagy in the spinal cord of SOD1 mutant mice. Autophagy. 2008;4:290–3. Epub 2008 Jan 7.
   PubMed Web of Science ®Google Scholar
• MacGowan DJ, Scelsa SN, Imperato TE, Liu KN, Baron P, Polsky B. A controlled study of reverse transcriptase in serum and CSF of HIV-negative patients with ALS. Neurology. 2007; 68: 1944–6
   PubMed Web of Science ®Google Scholar
• Steele AJ, Al-Chalabi A, Ferrante K, Cudkowicz ME, Brown RH, Jr, Garson JA. Detection of serum reverse transcriptase activity in patients with ALS and unaffected blood relatives. Neurology. 2005; 64: 454–8
   PubMed Web of Science ®Google Scholar
• McCormick AL, Brown RH, Jr, Cudkowicz ME, Al-Chalabi A, Garson JA. Quantification of reverse transcriptase in ALS and elimination of a novel retroviral candidate. Neurology. 2008; 70: 278–83
   PubMed Web of Science ®Google Scholar
• Rosen DR, Siddique T, Patterson D, Figlewicz DA, Sapp P, Hentati A, et al. Mutations in Cu/Zn superoxide dismutase are associated with familial amyotrophic lateral sclerosis. Nature. 1993; 362: 59–62
   PubMed Web of Science ®Google Scholar
• Ralph GS, Radcliffe PA, Day DM, Carthy JM, Leroux MA, Lee DCP, et al. Silencing mutant SOD1 using RNAi protects against neurodegeneration and extends survival in an ALS model. Nature Medicine. 2005; 11: 429–33
   PubMed Web of Science ®Google Scholar
• Xia X, Zhou H, Huang Y, Xu Z. Allele-specific RNAi selectively silences mutant SOD1 and achieves significant therapeutic benefit in vivo. Neurobiology of Disease. 2006; 23: 578–86
   PubMed Web of Science ®Google Scholar
• Hadano S, Hand C, Osuga H, Yanagisawa Y, Otomo A, Devon R, et al. A gene encoding a putative GTPase regulator is mutated in familial amyotrophic lateral sclerosis. Nat Genet. 2001; 29: 166–73
   PubMed Web of Science ®Google Scholar
• Puls I, Jonnakuty C, LaMonte B, Holzbaur E, Tokito M, Mann E, et al. Mutant dynactin in motor neuron disease. Nature Genetics. 2003; 33: 455–6
   PubMed Web of Science ®Google Scholar
• Chen Y-Z, Hashemi SH, Anderson SK, Huang Y, Moreira M-C, Lynch DR, et al. Senataxin, the yeast Sen1p orthologue: characterization of a unique protein in which recessive mutations cause ataxia and dominant mutations cause motor neuron disease. Neurobiology of Disease. 2006; 23: 97–108
   PubMed Web of Science ®Google Scholar
• Sreedharan J Blair IP Tripathi VB Hu X Vance C Rogelj B, et al TDP-43 mutations in familial and sporadic amyotrophic lateral sclerosis. Science. 2008. (Epub ahead of print).
   PubMed Web of Science ®Google Scholar
• Gitcho MA Baloh RH Chakraverty S Mayo K Norton JB Levitch D, et al TDP-43 A315T mutation in familial motor neuron disease. Annals of Neurology. 2008;9999: NA.
   Google Scholar
• Gurney ME, Pu H, Chiu AY, Dal Canto MC, Polchow CY, Alexander DD, et al. Motor neuron degeneration in mice that express a human Cu/Zn superoxide dismutase mutation. Science. 1994; 264: 1772–5
   PubMed Web of Science ®Google Scholar
• Kennel P, Revah F, Bohme GA, Bejuit R, Gallix P, Stutzmann J-M, et al. Riluzole prolongs survival and delays muscle strength deterioration in mice with progressive motor neuronopathy (pmn). J Neurol Sci. 2000; 180: 55–61
   PubMed Web of Science ®Google Scholar
• , Amyotrophic Lateral Sclerosis/Riluzole Study Group, IILacomblez L , Bensimon G , Meininger V , Leigh PN , Guillet P. Dose-ranging study of riluzole in amyotrophic lateral sclerosis. The Lancet. 1996;347:1425–31.
   PubMed Web of Science ®Google Scholar
• Fornai F , Longone P , Cafaro L , Kastsiuchenka O , Ferrucci M , Manca ML, et al Lithium delays progression of amyotrophic lateral sclerosis. Proceedings of the National Academy of Sciences. 2008: 0708022105.
   PubMed Web of Science ®Google Scholar
• Shefner JM, Cudkowicz ME, Schoenfeld D, Conrad T, Taft J, Chilton M, et al. A clinical trial of creatine in ALS. Neurology. 2004; 63: 1656–61
   PubMed Web of Science ®Google Scholar
• Gordon PH, Moore DH, Florence JM, Verheijde JL, Spitalny GM, Doorish C, et al. Results of the phase III randomized controlled trial of minocycline in ALS. Neurology. 2007; 68(Suppl 1)A90–1
   PubMed Web of Science ®Google Scholar
• Cudkowicz M, Shefner J, Schoenfeld D, Zhang H, Andreasson K, Rothstein J, et al. Trial of celecoxib in amyotrophic lateral sclerosis. Annals of Neurology. 2006; 60: 22–31
   PubMed Web of Science ®Google Scholar
• Miller R, Moore DH, Young L, Group WS. Placebo-controlled trial of gabapentin in patients with amyotrophic lateral sclerosis. Neurology. 1996; 47: 1383–8
   PubMed Web of Science ®Google Scholar
• Cudkowicz M, Shefner J, Schoenfeld D, Brown RJ, Johnson H, Qureshi M, et al. A randomized, placebo-controlled trial of topiramate in amyotrophic lateral sclerosis. Neurology. 2003; 61: 456–64
   PubMed Web of Science ®Google Scholar
• Desnuelle C, Dib M, Garrel C, Favier A. A double-blind, placebo-controlled randomized clinical trial of alpha-tocopherol (vitamin E) in the treatment of amyotrophic lateral sclerosis. ALS riluzole-tocopherol Study Group. Amyotrophic Lateral Sclerosis Other Motor Neuron Disorders. 2001; 2: 9–18
   PubMed Web of Science ®Google Scholar
• Klivenyi P, Ferrante R, Matthew R, Bogdanov M, Klein A, Mueller G, et al. Neuroprotective effects of creatine in a transgenic animal model of ALS. Nature Medicine. 1999; 5: 347–50
   PubMed Web of Science ®Google Scholar
• Zhu S, Stavrovskaya IG, Drozda M, Kim BY, Ona V, Li M, et al. Minocycline inhibits cytochrome c release and delays progression of amyotrophic lateral sclerosis in mice. Nature. 2002; 417: 74–8
   PubMed Web of Science ®Google Scholar
• Cudkowicz ME, Shefner JM, Schoenfeld DA, Brown RHJr, Johnson H, Qureshi M, et al. A randomized, placebo-controlled trial of topiramate in amyotrophic lateral sclerosis. Neurology. 2003; 61: 456–64
   PubMed Web of Science ®Google Scholar
• Drachman D, Frank K, Dykes-Hoberg M, Teismann P, Almer G, Przedborski S, et al. Cyclooxygenase 2 inhibition protects motor neurons and prolongs survival in a transgenic mouse model of ALS. Annals of Neurology. 2002; 52: 771–8
   PubMed Web of Science ®Google Scholar
• Alexander GM, Erwin KL, Byers N, Deitch JS, Augelli BJ, Blankenhorn EP, et al. Effect of transgene copy number on survival in the G93A SOD1 transgenic mouse model of ALS. Molecular Brain Research. 2004; 130: 7–15
   PubMedGoogle Scholar
• Scott S, Kranz JE, Cole J, Lincecum JM, Thompson K, Kelly N, et al. Design, power, and interpretation of studies in the standard murine model of ALS. Amyotrophic Lateral Sclerosis. 2008; 9: 4–15
   PubMed Web of Science ®Google Scholar
• Gordon PH, Moore DH, Gelinas DF, Qualls C, Meister ME, Werner J, et al. Placebo-controlled phase I/II studies of minocycline in amyotrophic lateral sclerosis. Neurology. 2004; 62: 1845–7
   PubMed Web of Science ®Google Scholar
• Bender A, Koch W, Elstner M, Schombacher Y, Bender J, Moeschl M, et al. Creatine supplementation in Parkinson's disease: a placebo-controlled randomized pilot trial. Neurology. 2006; 67: 1262–4
   PubMed Web of Science ®Google Scholar
• Tabrizi SJ, Blamire AM, Manners DN, Rajagopalan B, Styles P, Schapira AHV, et al. High-dose creatine therapy for Huntington's disease: a two-year clinical and MRS study. Neurology. 2005; 64: 1655–6
   PubMed Web of Science ®Google Scholar
• Ryu H, Smith K, Camelo SI, Carreras I, Lee J, Iglesias AH, et al. Sodium phenylbutyrate prolongs survival and regulates expression of anti-apoptotic genes in transgenic amyotrophic lateral sclerosis mice. Journal of Neurochemistry. 2005; 93: 1087–98
   PubMed Web of Science ®Google Scholar
• Cudkowicz ME Andres PL Choudry R MacDonald SA Zhang H Schoenfeld D, et al Safety and dose escalating study of oral sodium phenylbutyrate in subjects with ALS. Neurology. 2007;68(Suppl 1):A90 (Abstract).
   PubMed Web of Science ®Google Scholar
• Ranganathan S, Jordan K, Sathanoonri R, Henry S, Wood P, Urbinelli L, et al. Identification of ALS specific biomarkers by protein profiling of cerebral spinal fluid. ALS and Motor Neuron Disease. 2003; 4: 12
   Google Scholar
• Zetterberg H, Jacobsson J, Rosengren L, Blennow K, Andersen PM. Cerebrospinal fluid neurofilament light levels in amyotrophic lateral sclerosis: impact of SOD1 genotype. European Journal of Neurology. 2007; 14: 1329–33
   PubMed Web of Science ®Google Scholar
• Bruijn LI, Miller TM, Cleveland DW. Unraveling the mechanisms involved in motor neuron degeneration in ALS. Annu Rev Neurosci. 2004; 27: 723–49
   PubMed Web of Science ®Google Scholar
• Groeneveld GJ, Veldink JH, van der Tweel I, Kalmijn S, Beijer C, de Visser M, et al. A randomized sequential trial of creatine in amyotrophic lateral sclerosis. Annals of Neurology. 2003; 53: 437–45
   PubMed Web of Science ®Google Scholar
• Levy G, Kaufmann P, Buchsbaum R, Montes J, Barsdorf A, Arbing R, et al. A two-stage design for a phase II clinical trial of coenzyme Q10 in ALS. Neurology. 2006; 66: 660–3
   PubMed Web of Science ®Google Scholar
• Swartz A SJ, Yu H, Thornell B, Sherman A, Cudkowicz M. Design and implementation of a multi-phase, adaptive-design clinical trial for subjects with ALS. Amyotrophic Lateral Sclerosis. 2007; 8(Suppl 1)142–3
   Google Scholar
• Schoenfeld DA, Cudkowicz M. Design of phase II ALS clinical trials. Amyotrophic Lateral Sclerosis. 2008; 9: 16–23
   PubMed Web of Science ®Google Scholar
• Miller R, Bradley W, Cudkowicz M, Hubble J, Meininger V, Mitsumoto H, et al. Phase II/III randomized trial of TCH346 in patients with ALS. Neurology. 2007; 69: 776–84
   PubMed Web of Science ®Google Scholar
• Meininger V, Bensimon G, Bradley WG, Brooks BR, Douillet P, Eisen AA, et al. Efficacy and safety of xaliproden in amyotrophic lateral sclerosis: results of two phase III trials. Amyotroph Lateral Scler Other Motor Neuron Disord. 2004; 5: 107–17
   PubMed Web of Science ®Google Scholar
• Meininger V. Clinical Trials in ALS: What Did We Learn from Recent Trials in Humans?. Neurodegenerative Diseases. 2005; 2: 208–14
   PubMed Web of Science ®Google Scholar
• Piepers S, van den Berg J-P, Kalmijn S, van ver Pol WL, Wokke JHJ, Lindeman E, et al. Effect of non-invasive ventilation on survival, quality of life, respiratory function and cognition: a review of the literature. Amyotrophic Lateral Sclerosis. 2006; 7: 195–200
   PubMed Web of Science ®Google Scholar
• Mazzini L, Corra T, Zaccala M, Mora G, Del Piano M, Galante M. Percutaneous endoscopic gastrostomy and enteral nutrition in amyotrophic lateral sclerosis. J Neurol Neurosurg Psychiatry. 1995; 242: 695–8
   Google Scholar
• Bensimon G Lacomblez L Meininger V The ALS Riluzole Study Group. A controlled trial of riluzole in amyotrophic lateral sclerosis. N Engl J Med. 1994;330:585–91.
   PubMed Web of Science ®Google Scholar
• Miller RG, Moore DH, Gelinas DF, Dronsky B, Mendoza M, Barohn R, et al. Phase III randomized trial of gabapentin in patients with amyotrophic lateral sclerosis. Neurology. 2001; 56: 843–8
   PubMed Web of Science ®Google Scholar
• Eisen A, Stewart H, Schulzer M, Cameron D. Anti-glutamate therapy in amyotrophic lateral sclerosis: a trial using lamotrigine. The Canadian Journal of Neurological Sciences. 1993; 20: 297–301
   PubMed Web of Science ®Google Scholar
• Ryberg H, Askmark H, Persson LI. A double-blind randomized clinical trial in amyotrophic lateral sclerosis using lamotrigine: effects on CSF glutamate, aspartate, branched-chain amino acid levels and clinical parameters. Acta Neurologica Scandinavica. 2003; 108: 1–8
   PubMed Web of Science ®Google Scholar
• Gredal O, Werdelin L, Bak S, Christensen PB, Boysen G, Kristensen MO, et al. A clinical trial of dextromethorphan in amyotrophic lateral sclerosis. Acta Neurologica Scandinavica. 1997; 96: 8–13
   PubMed Web of Science ®Google Scholar
• ALS CNTF Treatment Study Group. A double-blind placebo-controlled clinical trial of subcutaneous recombinant human ciliary neurotrophic factor (rhCNTF) in amyotrophic lateral sclerosis. Neurol. 1996;46:1244–9.
   PubMed Web of Science ®Google Scholar
• Miller R, Petajan J, Bryan W, Armon C, Barohn R, Goodpasture J, et al. A placebo-controlled trial of recombinant human ciliary neurotrophic (rhCNTF) factor in amyotrophic lateral sclerosis. Ann Neurol. 1996; 39: 256–60
   PubMed Web of Science ®Google Scholar
• Borasio GD, Robberecht W, Leigh PN, Emile J, Guiloff RJ, Jerusalem F, et al. A placebo-controlled trial of insulin-like growth factor-I in amyotrophic lateral sclerosis. European ALS/IGF-I Study Group. Neurology. 1998; 2: 583–6
   Google Scholar
• The BDNF Study Group. A controlled trial of recombinant methionyl human BDNF in ALS. Neurology. 1999;52:1427–33.
   PubMed Web of Science ®Google Scholar
• Munsat T, Taft J, Jackson I, Andres P, Hollander D, Skerry L, et al. Intrathecal thyrotropin-releasing hormone does not alter the progressive course of ALS: experience with an intrathecal drug delivery system. Neurol. 1992; 42: 1049–53
   PubMed Web of Science ®Google Scholar
• Brooke MH, Florence JM, Heller SL, Kaiser KK, Phillips D, Gruber A, et al. Controlled trial of thyrotropin releasing hormone in amyotrophic lateral sclerosis. Neurology. 1986; 36: 146–51
   PubMed Web of Science ®Google Scholar
• Graf M, Ecker D, Horowski R, Kramer B, Riederer P, Gerlach M, et al. High dose vitamin E therapy in amyotrophic lateral sclerosis as add-on therapy to riluzole: results of a placebo-controlled double-blind study. Journal of Neural Transmission. 2005; 112: 649–60
   PubMed Web of Science ®Google Scholar
• Louwerse ES, Weverling GJ, Bossuyt PM, Meyjes FE, de Jong JM. Randomized, double-blind, controlled trial of acetylcysteine in amyotrophic lateral sclerosis. Arch Neurol. 1995; 52: 559–64
   PubMed Web of Science ®Google Scholar
• Lange D, Peregrine L, Murphy M, Diamond B, Appel V, Lai E, et al. Selegiline is ineffective in a collaborative double-blind, placebo-controlled trial for treatment of amyotrophic lateral sclerosis. Arch Neurol. 1998; 55: 93–6
   PubMed Web of Science ®Google Scholar
• Ferrante KL, Shefner J, Zhang H, Betensky R, O'Brien M, Yu H, et al. Tolerance of high-dose (3000 mg/day) coenzyme Q10 in ALS. Neurology. 2005; 65: 1834–6
   PubMed Web of Science ®Google Scholar
• Shefner JM, Cudkowicz ME, Schoenfeld D, Conrad T, Taft J, Chilton M, et al. A clinical trial of creatine in amyotrophic lateral sclerosis. Neurology. 2004; 63: 1656–61
   PubMed Web of Science ®Google Scholar
• The Italian ALS Study Group. Branched-chain amino acids and amyotrophic lateral sclerosis: a treatment failure? Neurology. 1993;43:2466–70.
   PubMed Web of Science ®Google Scholar
• Tandan R, Bromberg MB, Forshew D, Fries TJ, Badger GJ, Carpenter J, et al. A controlled trial of amino acid therapy in amyotrophic lateral sclerosis: I. Clinical, functional, and maximum isometric torque data. Neurology. 1996; 47: 1220–6
   PubMed Web of Science ®Google Scholar
• Miller RG, Shepherd R, Dao H, Khramstov A, Mendoza M, Graves J, et al. Controlled trial of nimodipine in amyotrophic lateral sclerosis. Neuromuscular Disorders. 1996; 6: 101–4
   PubMed Web of Science ®Google Scholar
• Miller RG, Smith SA, Murphy JR, Brinkmann JR, Graves J, Mendoza M, et al. A clinical trial of verapamil in amyotrophic lateral sclerosis. Muscle & Nerve. 1996; 19: 511–5
   PubMed Web of Science ®Google Scholar
• Meininger V, Asselain B, Guillet P, Leigh PN, Ludolph A, Lacomblez L, et al. Pentoxifylline in ALS: a double-blind, randomized, multicenter, placebo-controlled trial. Neurology. 2006; 66: 88–92
   PubMed Web of Science ®Google Scholar
• Gordon PH, Moore DH, Miller RG, Florence JM, Verheijde JL, Doorish C, et al. Efficacy of minocycline in patients with amyotrophic lateral sclerosis: a phase III randomized trial. The Lancet Neurology. 2007; 6: 1045–53
   PubMed Web of Science ®Google Scholar
• Gourie-Devi M, Nalini A, Subbakrishna DK. Temporary amelioration of symptoms with intravenous cyclophosphamide in amyotrophic lateral sclerosis. J Neurol Sci. 1997; 150: 167–72
   PubMed Web of Science ®Google Scholar
• Bradley WG Hedlund W Cooper C Desousa GJ Gabbai A Mora JS, et al A double-blind controlled trial of bovine brain gangliosides in amyotrophic lateral sclerosis. Neurol. 1984;34.
   PubMed Web of Science ®Google Scholar
• Harrington H, Hallett M, Tyler HR. Ganglioside therapy for amyotrophic lateral sclerosis: a double-blind controlled trial. Neurology. 1984; 34: 1083–5
   PubMed Web of Science ®Google Scholar
• Beghi E, Chio A, Inghilleri M, Mazzini L, Micheli A, Mora G, et al. A randomized controlled trial of recombinant interferon beta-1a in ALS. Neurology. 2000; 54: 469
   PubMed Web of Science ®Google Scholar
• Chili A, Cucatto A, Terreni A, Schiffer D. Reduced glutathione in amyotrophic lateral sclerosis: an open, cross-over, randomized trial. The Italian Journal of Neurological Sciences. 1998; 19: 363–6
   PubMedGoogle Scholar
• Rutkove SB, Parker RA, Nardin RA, Connolly CE, Felice KJ, Raynor EM. A pilot randomized trial of oxandrolone in inclusion body myositis. Neurology. 2002; 58: 1081–7
   PubMed Web of Science ®Google Scholar
• Brooks B. Tamoxifen phase II dose-escalation clinical trial in ALS: study design and safety results in first 50 patients. 2003, November 17–19; a report from the 14th International Symposium on ALS/MND. http://wwwalsaorg/patient/articlecfm?id=217&CFID=2&CFTOKEN=68144428#Tamoxifen.
   Google Scholar
• Beck M, Karch C, Wiese S, Sendtner M. Motor neuron cell death and neurotrophic factors: basic models for development of new therapeutic strategies in ALS. Amyotrophic Lateral Scler Other Motor Neuron Disord. 2001; 2(Suppl 1)55–68
   Google Scholar
• Ghadge GD, Wang L, Sharma K, Monti AL, Bindokas V, Stevens FJ, et al. Truncated wild-type SOD1 and FALS-linked mutant SOD1 cause neural cell death in the chick embryo spinal cord. Neurobiology of Disease. 2006; 21: 194–205
   PubMed Web of Science ®Google Scholar
• Silani V, Braga M, Ciammola A, Cardin V, Scarlato G. Motor neurons in culture as a model to study ALS. Journal of Neurology. 2000; 247(Suppl 1)36
   Google Scholar
• Matyja E, Taraszewska A, Naganska E, Rafalowska J, Gebarowska J. Astroglial alterations in amyotrophic lateral sclerosis (ALS) model of slow glutamate excitotoxicity in vitro. Folia Neuropathology. 2005; 43: 7–13
   PubMed Web of Science ®Google Scholar
• Di Giorgio FP, Carrasco MA, Siao MC, Maniatis T, Eggan K. Non-cell autonomous effect of glia on motor neurons in an embryonic stem cell-based ALS model. Nat Neurosci. 2007; 10: 608–14
   PubMed Web of Science ®Google Scholar
• Virgo L, Dekkers J, Mentis GZ, Navarrete R, de Belleroche J. Changes in expression of NMDA receptor subunits in the rat lumbar spinal cord following neonatal nerve injury. Neuropathology & Applied Neurobiology. 2000; 26: 258–72
   PubMed Web of Science ®Google Scholar
• Avossa D, Grandolfo M, Mazzarol F, Zatta M, Ballerini L. Early signs of motor neuron vulnerability in a disease model system: characterization of transverse slice cultures of spinal cord isolated from embryonic ALS mice. Neuroscience. 2006; 138: 1179–94
   PubMed Web of Science ®Google Scholar
• Olivieri G, Baysang G, Meier F, Muller-Spahn F, Stahelin HB, Brockhaus M, et al. N-Acetyl-l-cysteine protects SHSY5Y neuroblastoma cells from oxidative stress and cell cytotoxicity: effects on beta-amyloid secretion and tau phosphorylation. Journal of Neurochemistry. 2001; 76: 224–33
   PubMed Web of Science ®Google Scholar
• Park K-S, Kim H-J, Choi W-J, Kim M, Lee K-W. Detection method of the adjacent motor neuronal death in an in vitro coculture model of familial ALS-associated Cu/Zn superoxide dismutase. Biotechnology Letters. 2004; 26: 1201–5
   PubMed Web of Science ®Google Scholar
• Liu R, Narla RK, Kurinov I, Li B, Uckun FM. Increased hydroxyl radical production and apoptosis in PC12 neuron cells expressing the gain-of-function mutant G93A SOD1 gene. Radiation Research. 1999; 151: 133–41
   PubMed Web of Science ®Google Scholar
• Haenggeli C, Kato AC. Differential vulnerability of cranial motor neurons in mouse models with motor neuron degeneration. Neuroscience Letters. 2002; 335: 39–43
   PubMed Web of Science ®Google Scholar
• Doble A, Kennel P. Animal models of amyotrophic lateral sclerosis. Amyotrophic Lateral Scler Other Motor Neuron Disord. 2000; 1: 301–12
   PubMed Web of Science ®Google Scholar
• Nagai M, Aoki M, Miyoshi I, Kato M, Pasinelli P, Kasai N, et al. Rats expressing human cytosolic copper-zinc superoxide dismutase transgenes with amyotrophic lateral sclerosis: associated mutations develop motor neuron disease. J Neurosci. 2001; 23: 9246–54
   Google Scholar
• Watabe K. Proximal axonal injuries as experimental models for adult motor neuron degeneration. Brain Nerve. 2007; 59: 1179–86
   PubMedGoogle Scholar
• LaMonte BH, Wallace KE, Holloway BA, Shelly SS, Ascano J, Tokito M, et al. Disruption of dynein/dynactin inhibits axonal transport in motor neurons causing late-onset progressive degeneration. Neuron. 2002; 34: 715–27
   PubMed Web of Science ®Google Scholar
• Kwak S, Nakamura R. Acute and late neurotoxicity in the rat spinal cord in vivo induced by glutamate receptor agonists. J Neurol Sci. 1995; 129: 99–103
   PubMed Web of Science ®Google Scholar
• Oosthuyse B, Moons L, Storkebaum E, Beck H, Nuyens D, Brusselmans K, et al. Deletion of the hypoxia-response element in the vascular endothelial growth factor promoter causes motor neuron degeneration. Nat Genet. 2001; 28: 131–8
   PubMed Web of Science ®Google Scholar
• Rockenstein E, Crews L, Masliah E. Transgenic animal models of neurodegenerative diseases and their application to treatment development. Advanced Drug Delivery Reviews. 2007; 59: 1093–102
   PubMed Web of Science ®Google Scholar
• Shulman JM, Shulman LM, Weiner WJ, Feany MB. From fruit fly to bedside: translating lessons from Drosophila models of neurodegenerative disease. 2003; 16: 443–9
   Google Scholar
• Cork LC, Kitt CA, Struble RG, Griffin JW, Price DL. Animal models of degenerative neurological disease. Progress in Clinical and Biological Research. 1987; 229: 241–69
   PubMedGoogle Scholar
• Zoccolella S, Simone IL, Lamberti P, Samarelli V, Tortelli R, Serlenga L, et al. Elevated plasma homocysteine levels in patients with amyotrophic lateral sclerosis. Neurology. 2008; 70: 222–5
   PubMed Web of Science ®Google Scholar
• Demestre M, Parkin-Smith G, Petzold A, Pullen AH. The pro and the active form of matrix metalloproteinase-9 is increased in serum of patients with amyotrophic lateral sclerosis. Journal of Neuroimmunology. 2005; 159: 146–54
   PubMed Web of Science ®Google Scholar
• Houi K, Kobayashi T, Kato S, Mochio S, Inoue K. Increased plasma TGF-1 in patients with amyotrophic lateral sclerosis. Acta Neurologica Scandinavica. 2002; 106: 299–301
   PubMed Web of Science ®Google Scholar
• Ilzecka J. Cerebrospinal fluid Flt3 ligand level in patients with amyotrophic lateral sclerosis. Acta Neurologica Scandinavica. 2006; 114: 205–9
   PubMed Web of Science ®Google Scholar
• Pasinetti GM, Ungar LH, Lange DJ, Yemul S, Deng H, Yuan X, et al. Identification of potential CSF biomarkers in ALS. Neurology. 2006; 66: 1218–22
   PubMed Web of Science ®Google Scholar
• Tsuboi Y, Yamada T. Increased concentration of C4d complement protein in CSF in amyotrophic lateral sclerosis. J Neurol Neurosurg Psychiatry. 1994; 57: 859–61
   PubMed Web of Science ®Google Scholar
• Sekizawa T, Openshaw H, Ohbo K, Sugamura K, Itoyama Y, Niland JC. Cerebrospinal fluid interleukin 6 in amyotrophic lateral sclerosis: immunological parameter and comparison with inflammatory and non-inflammatory central nervous system diseases. J Neurol Sci. 1998; 154: 194–9
   PubMed Web of Science ®Google Scholar
• Nagata T, Nagano I, Shiote M, Narai H, Murakami T, Hayashi T, et al. Elevation of MCP-1 and MCP-1/VEGF ratio in cerebrospinal fluid of amyotrophic lateral sclerosis patients. Neurological Research. 2007; 29: 772–6
   PubMed Web of Science ®Google Scholar
• Baron P, Bussini S, Cardin V, Corbo M, Conti G, Galimberti D, et al. Production of monocyte chemoattractant protein-1 in amyotrophic lateral sclerosis. Muscle & Nerve. 2005; 32: 541–4
   PubMed Web of Science ®Google Scholar
• Bogdanov M, Brown RH, Matson W, Smart R, Hayden D, O'Donnell H, et al. Increased oxidative damage to DNA in ALS patients. Free Radical Biology and Medicine. 2000; 29: 652–8
   PubMed Web of Science ®Google Scholar
• Simpson EP, Henry YK, Henkel JS, Smith RG, Appel SH. Increased lipid peroxidation in sera of ALS patients: a potential biomarker of disease burden. Neurology. 2004; 62: 1758–65
   PubMed Web of Science ®Google Scholar
• Ilzecka J. Prostaglandin E2 is increased in amyotrophic lateral sclerosis patients. Acta Neurologica Scandinavica. 2003; 108: 125–9
   PubMed Web of Science ®Google Scholar
• Pradat PF, Bruneteau G, Gonzalez de Aguilar JL, Dupuis L, Jokic N, Salachas F, et al. Muscle Nogo-a expression is a prognostic marker in lower motor neuron syndromes. Annals of Neurology. 2007; 62: 15–20
   PubMed Web of Science ®Google Scholar