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Review

Amyotrophic lateral sclerosis: clinical perspectives

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Pages 19-31 | Published online: 15 Apr 2015

References

  • Noonan CW, White MC, Thurman D, Wong LY. Temporal and geographic variation in United States motor neuron disease mortality, 1969–1998. Neurology. 2005;64(7):1215–1221.
  • Rowland LP, Shneider NA. Amyotrophic lateral sclerosis. N Engl J Med. 2001;344(22):1688–1700.
  • Renton AE, Chio A, Traynor BJ. State of play in amyotrophic lateral sclerosis genetics. Nat Neurosci. 2014;17(1):17–23.
  • Chiò A, Mora G, Calvo A, et al. Epidemiology of ALS in Italy: a 10-year prospective population-based study. Neurology. 2009;72(8):725–731.
  • Strong MJ, Grace GM, Freedman M, et al. Consensus criteria for the diagnosis of frontotemporal cognitive and behavioural syndromes in amyotrophic lateral sclerosis. Amyotroph Lateral Scler. 2009;10(3):131–146.
  • Rohrer JD, Isaacs AM, Mizlienska S, et al. C9orf72 expansions in frontotemporal dementia and amyotrophic lateral sclerosis. Lancet Neurol. 2015;14(3):291–301.
  • Morris HR, Waite AJ, Williams NM, Neal JW, Blake DJ. Recent advances in the genetics of the ALS-FTLD complex. Curr Neurol Neurosci Rep. 2012;12(3):243–250.
  • Siddique T, Nijhawan D, Hentati A. Molecular genetic basis of familial ALS. Neurology. 1996;47(4 Suppl 2):S27–S34. [discussion S34–S25].
  • Rosen DR, Siddique T, Patterson D, et al. Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis. Nature. 1993;362(6415):59–62.
  • Robberecht W, Philips T. The changing scene of amyotrophic lateral sclerosis. Nat Rev Neurosci. 2013;14(4):248–264.
  • Sreedharan J, Blair IP, Tripathi VB, et al. TDP-43 mutations in familial and sporadic amyotrophic lateral sclerosis. Science. 2008;319(5870):1668–1672.
  • Kwiatkowski TJ Jr, Bosco DA, Leclerc AL, et al. Mutations in the FUS/TLS gene on chromosome 16 cause familial amyotrophic lateral sclerosis. Science. 2009;323(5918):1205–1208.
  • Renton AE, Majounie E, Waite A, et al; ITALSGEN Consortium. A hexanucleotide repeat expansion in C9ORF72 is the cause of chromosome 9p21-linked ALS-FTD. Neuron. 2011;72(2):257–268.
  • Majounie E, Renton AE, Mok K, et al; Chromosome 9-ALS/FTD Consortium, French Research Network on FTLD/FTLD/ALS, ITALSGEN Consortium. Frequency of the C9orf72 hexanucleotide repeat expansion in patients with amyotrophic lateral sclerosis and frontotemporal dementia: a cross-sectional study. Lancet Neurol. 2012;11(4):323–330.
  • Kabashi E, Valdmanis PN, Dion P, et al. TARDBP mutations in individuals with sporadic and familial amyotrophic lateral sclerosis. Nat Genet. 2008;40(5):572–574.
  • Neumann M, Sampathu DM, Kwong LK, et al. Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Science. 2006;314(5796):130–133.
  • Al-Chalabi A, Leigh PN. Recent advances in amyotrophic lateral sclerosis. Curr Opin Neurol. 2000;13(4):397–405.
  • Bensimon G, Lacomblez L, Meininger V. A controlled trial of riluzole in amyotrophic lateral sclerosis. ALS/Riluzole Study Group. N Engl J Med. 1994;330(9):585–591.
  • Bensimon G, Lacomblez L, Delumeau JC, et al; Riluzole/ALS Study Group II. A study of riluzole in the treatment of advanced stage or elderly patients with amyotrophic lateral sclerosis. J Neurol. 2002;249(5):609–615.
  • Miller RG, Mitchell JD, Moore DH. Riluzole for amyotrophic lateral sclerosis (ALS)/motor neuron disease (MND). Cochrane Database Syst Rev. 2012;3:CD001447.
  • Perel P, Roberts I, Sena E, et al. Comparison of treatment effects between animal experiments and clinical trials: systematic review. BMJ. 2007;334(7586):197.
  • Gurney ME, Pu H, Chiu AY, et al. Motor neuron degeneration in mice that express a human Cu,Zn superoxide dismutase mutation. Science. 1994;264(5166):1772–1775.
  • Zhou H, Huang C, Chen H, et al. Transgenic rat model of neurodegeneration caused by mutation in the TDP gene. PLoS Genet. 2010;6(3):e1000887.
  • Saxena S, Cabuy E, Caroni P. A role for motoneuron subtype-selective ER stress in disease manifestations of FALS mice. Nat Neurosci. 2009;12(5):627–636.
  • Miller TM, Pestronk A, David W, et al. An antisense oligonucleotide against SOD1 delivered intrathecally for patients with SOD1 familial amyotrophic lateral sclerosis: a phase 1, randomised, first-in-man study. Lancet Neurol. 2013;12(5):435–442.
  • Southwell AL, Skotte NH, Bennett CF, Hayden MR. Antisense oligonucleotide therapeutics for inherited neurodegenerative diseases. Trends Mol Med. 2012;18(11):634–643.
  • Miller TR, Wetter JB, Jarvis MF, Bitner RS. Spinal microglial activation in rat models of neuropathic and osteoarthritic pain: an autoradiographic study using [3H]PK11195. Eur J Pain. 2013;17(5):692–703.
  • Smith RA, Miller TM, Yamanaka K, et al. Antisense oligonucleotide therapy for neurodegenerative disease. J Clin Invest. 2006;116(8):2290–2296.
  • Lagier-Tourenne C, Baughn M, Rigo F, et al. Targeted degradation of sense and antisense C9orf72 RNA foci as therapy for ALS and frontotemporal degeneration. Proc Natl Acad Sci U S A. 2013;110(47):E4530–E4539.
  • Thomsen GM, Gowing G, Svendsen S, Svendsen CN. The past, present and future of stem cell clinical trials for ALS. Exp Neurol. 2014;262(pt B):127–137.
  • Kudoh T, Concha ML, Houart C, Dawid IB, Wilson SW. Combinatorial Fgf and Bmp signalling patterns the gastrula ectoderm into prospective neural and epidermal domains. Development. 2004;131(15):3581–3592.
  • Ohtsuka T, Shimojo H, Matsunaga M, et al. Gene expression profiling of neural stem cells and identification of regulators of neural differentiation during cortical development. Stem Cells. 2011;29(11):1817–1828.
  • Okabe S, Forsberg-Nilsson K, Spiro AC, Segal M, McKay RD. Development of neuronal precursor cells and functional postmitotic neurons from embryonic stem cells in vitro. Mech Dev. 1996;59(1):89–102.
  • Wu YY, Mujtaba T, Rao MS. Isolation of stem and precursor cells from fetal tissue. Methods Mol Biol. 2002;198:29–40.
  • Yan J, Xu L, Welsh AM, et al. Extensive neuronal differentiation of human neural stem cell grafts in adult rat spinal cord. PLoS Med. 2007;4(2):e39.
  • Lee HJ, Kim KS, Ahn J, Bae HM, Lim I, Kim SU. Human motor neurons generated from neural stem cells delay clinical onset and prolong life in ALS mouse model. PLoS One. 2014;9(5):e97518.
  • Xu L, Yan J, Chen D, et al. Human neural stem cell grafts ameliorate motor neuron disease in SOD-1 transgenic rats. Transplantation. 2006;82(7):865–875.
  • Guo X, Johe K, Molnar P, Davis H, Hickman J. Characterization of a human fetal spinal cord stem cell line, NSI-566RSC, and its induction to functional motoneurons. J Tissue Eng Regen Med. 2010;4(3):181–193.
  • Feldman EL, Boulis NM, Hur J, et al. Intraspinal neural stem cell transplantation in amyotrophic lateral sclerosis: phase 1 trial outcomes. Ann Neurol. 2014;75(3):363–373.
  • Franco Lambert AP, Fraga Zandonai A, Bonatto D, Cantarelli Machado D, Pegas Henriques JA. Differentiation of human adipose-derived adult stem cells into neuronal tissue: does it work? Differentiation. 2009;77(3):221–228.
  • Knippenberg S, Thau N, Dengler R, Brinker T, Petri S. Intracerebroventricular injection of encapsulated human mesenchymal cells producing glucagon-like peptide 1 prolongs survival in a mouse model of ALS. PLoS One. 2012;7(6):e36857.
  • Suzuki M, McHugh J, Tork C, et al. Direct muscle delivery of GDNF with human mesenchymal stem cells improves motor neuron survival and function in a rat model of familial ALS. Mol Ther. 2008;16(12):2002–2010.
  • Krakora D, Mulcrone P, Meyer M, et al. Synergistic effects of GDNF and VEGF on lifespan and disease progression in a familial ALS rat model. Mol Ther. 2013;21(8):1602–1610.
  • Bigini P, Veglianese P, Andriolo G, et al. Intracerebroventricular administration of human umbilical cord blood cells delays disease progression in two murine models of motor neuron degeneration. Rejuvenation Res. 2011;14(6):623–639.
  • Petrou P, Argov A, Lennon VA, et al. Rare combination of myasthenia and motor neuronopathy, responsive to Msc-Ntf stem cell therapy. Muscle Nerve. 2014;49(3):455–457.
  • Mazzini L, Vercelli A, Ferrero I, Boido M, Cantello R, Fagioli F. Transplantation of mesenchymal stem cells in ALS. Prog Brain Res. 2012;201:333–359.
  • Deda H, Inci MC, Kürekçi AE, et al. Treatment of amyotrophic lateral sclerosis patients by autologous bone marrow-derived hematopoietic stem cell transplantation: a 1-year follow-up. Cytotherapy. 2009;11(1):18–25.
  • Martínez HR, Molina-Lopez JF, González-Garza MT, et al. Stem cell transplantation in amyotrophic lateral sclerosis patients: methodological approach, safety, and feasibility. Cell Transplant. 2012;21(9):1899–1907.
  • Blanquer M, Moraleda JM, Iniesta F, et al. Neurotrophic bone marrow cellular nests prevent spinal motoneuron degeneration in amyotrophic lateral sclerosis patients: a pilot safety study. Stem Cells. 2012;30(6):1277–1285.
  • Karussis D, Karageorgiou C, Vaknin-Dembinsky A, et al. Safety and immunological effects of mesenchymal stem cell transplantation in patients with multiple sclerosis and amyotrophic lateral sclerosis. Arch Neurol. 2010;67(10):1187–1194.
  • Baek W, Kim YS, Koh SH, et al. Stem cell transplantation into the intraventricular space via an Ommaya reservoir in a patient with amyotrophic lateral sclerosis. J Neurosurg Sci. 2012;56(3):261–263.
  • Cashman N, Tan LY, Krieger C, et al. Pilot study of granulocyte colony stimulating factor (G-CSF)-mobilized peripheral blood stem cells in amyotrophic lateral sclerosis (ALS). Muscle Nerve. 2008;37(5):620–625.
  • Nefussy B, Artamonov I, Deutsch V, Naparstek E, Nagler A, Drory VE. Recombinant human granulocyte-colony stimulating factor administration for treating amyotrophic lateral sclerosis: a pilot study. Amyotroph Lateral Scler. 2010;11(1–2):187–193.
  • Grassinger J, Khomenko A, Hart C, et al. Safety and feasibility of long term administration of recombinant human granulocyte-colony stimulating factor in patients with amyotrophic lateral sclerosis. Cytokine. 2014;67(1):21–28.
  • Tarella C, Rutella S, Gualandi F, et al; STEMALS Study Group. Consistent bone marrow-derived cell mobilization following repeated short courses of granulocyte-colony-stimulating factor in patients with amyotrophic lateral sclerosis: results from a multicenter prospective trial. Cytotherapy. 2010;12(1):50–59.
  • Chio A, Mora G, La Bella V, et al. Repeated courses of granulocyte colony-stimulating factor in amyotrophic lateral sclerosis: clinical and biological results from a prospective multicenter study. Muscle Nerve. 2011;43(2):189–195.
  • Weiler E, Farbman AI. Proliferation in the rat olfactory epithelium: age-dependent changes. J Neurosci. 1997;17(10):3610–3622.
  • Ruitenberg MJ, Vukovic J, Sarich J, Busfield SJ, Plant GW. Olfactory ensheathing cells: characteristics, genetic engineering, and therapeutic potential. J Neurotrauma. 2006;23(3–4):468–478.
  • Ramon-Cueto A, Cordero MI, Santos-Benito FF, Avila J. Functional recovery of paraplegic rats and motor axon regeneration in their spinal cords by olfactory ensheathing glia. Neuron. 2000;25(2):425–435.
  • Mackay-Sim A, St John JA. Olfactory ensheathing cells from the nose: clinical application in human spinal cord injuries. Exp Neurol. 2011;229(1):174–180.
  • Li Y, Bao J, Khatibi NH, et al. Olfactory ensheathing cell transplantation into spinal cord prolongs the survival of mutant SOD1(G93A) ALS rats through neuroprotection and remyelination. Anat Rec. 2011;294(5):847–857.
  • Lunn JS, Sakowski SA, Feldman EL. Concise review: stem cell therapies for amyotrophic lateral sclerosis: recent advances and prospects for the future. Stem Cells. 2014;32(5):1099–1109.
  • Huang H, Chen L, Xi H, et al. Fetal olfactory ensheathing cells transplantation in amyotrophic lateral sclerosis patients: a controlled pilot study. Clin Transplant. 2008;22(6):710–718.
  • Chen L, Huang H, Zhang J, et al. Short-term outcome of olfactory ensheathing cells transplantation for treatment of amyotrophic lateral sclerosis. Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi. 2007;21(9):961–966.
  • Chen L, Chen D, Xi H, et al. Olfactory ensheathing cell neurorestorotherapy for amyotrophic lateral sclerosis patients: benefits from multiple transplantations. Cell Transplant. 2012;21(Suppl 1):S65–S77.
  • Piepers S, van den Berg LH. No benefits from experimental treatment with olfactory ensheathing cells in patients with ALS. Amyotroph Lateral Scler. 2010;11(3):328–330.
  • Giordana MT, Grifoni S, Votta B, et al. Neuropathology of olfactory ensheathing cell transplantation into the brain of two amyotrophic lateral sclerosis (ALS) patients. Brain Pathol. 2010;20(4):730–737.
  • Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 2006;126(4):663–676.
  • Takahashi K, Tanabe K, Ohnuki M, et al. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell. 2007;131(5):861–872.
  • Okita K, Ichisaka T, Yamanaka S. Generation of germline-competent induced pluripotent stem cells. Nature. 2007;448(7151):313–317.
  • Boulting GL, Kiskinis E, Croft GF, et al. A functionally characterized test set of human induced pluripotent stem cells. Nat Biotechnol. 2011;29(3):279–286.
  • Karumbayaram S, Novitch BG, Patterson M, et al. Directed differentiation of human-induced pluripotent stem cells generates active motor neurons. Stem Cells. 2009;27(4):806–811.
  • Yamanaka S. A fresh look at iPS cells. Cell. 2009;137(1):13–17.
  • Popescu IR, Nicaise C, Liu S, et al. Neural progenitors derived from human induced pluripotent stem cells survive and differentiate upon transplantation into a rat model of amyotrophic lateral sclerosis. Stem Cells Transl Med. 2013;2(3):167–174.
  • Nizzardo M, Simone C, Falcone M, et al. Direct reprogramming of adult somatic cells into other lineages: past evidence and future perspectives. Cell Transplant. 2013;22(6):921–944.
  • Kondo T, Funayama M, Tsukita K, et al. Focal transplantation of human iPSC-derived glial-rich neural progenitors improves lifespan of ALS mice. Stem Cell Rep. 2014;3(2):242–249.
  • Burkhardt MF, Martinez FJ, Wright S, et al. A cellular model for sporadic ALS using patient-derived induced pluripotent stem cells. Mol Cell Neurosci. 2013;56:355–364.
  • Chestkov IV, Vasilieva EA, Illarioshkin SN, Lagarkova MA, Kiselev SL. Patient-specific induced pluripotent stem cells for SOD1-associated amyotrophic lateral sclerosis pathogenesis studies. Acta Naturae. 2014;6(1):54–60.
  • Dimos JT, Rodolfa KT, Niakan KK, et al. Induced pluripotent stem cells generated from patients with ALS can be differentiated into motor neurons. Science. 2008;321(5893):1218–1221.
  • Yao XL, Ye CH, Liu Q, et al. Motoneuron differentiation of induced pluripotent stem cells from SOD1G93A mice. PLoS One. 2013;8(5):e64720.
  • Traynor BJ, Alexander M, Corr B, Frost E, Hardiman O. Effect of a multidisciplinary amyotrophic lateral sclerosis (ALS) clinic on ALS survival: a population based study, 1996–2000. J Neurol Neurosurg Psychiatry. 2003;74(9):1258–1261.
  • Chio A, Bottacchi E, Buffa C, Mutani R, Mora G; Parals. Positive effects of tertiary centres for amyotrophic lateral sclerosis on outcome and use of hospital facilities. J Neurol Neurosurg Psychiatry. 2006;77(8):948–950.
  • Aridegbe T, Kandler R, Walters SJ, Walsh T, Shaw PJ, McDermott CJ. The natural history of motor neuron disease: assessing the impact of specialist care. Amyotroph Lateral Scler Frontotemporal Degener. 2013;14(1):13–19.
  • Van den Berg JP, Kalmijn S, Lindeman E, et al. Multidisciplinary ALS care improves quality of life in patients with ALS. Neurology. 2005;65(8):1264–1267.
  • Miller RG, Jackson CE, Kasarskis EJ, et al; Quality Standards Subcommittee of the American Academy of Neurology. Practice parameter update: the care of the patient with amyotrophic lateral sclerosis: multidisciplinary care, symptom management, and cognitive/behavioral impairment (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2009;73(15):1227–1233.
  • EFNS Task Force on Diagnosis and Management of Amyotrophic Lateral Sclerosis; Andersen PM, Abrahams S, et al. EFNS guidelines on the clinical management of amyotrophic lateral sclerosis (MALS) – revised report of an EFNS task force. Eur J Neurol. 2012;19(3):360–375.
  • Eidenberger M, Nowotny S. Inspiratory muscle training in patients with amyotrophic lateral sclerosis: a systematic review. Neurorehabilitation. 2014;35(3):349–361.
  • Mustfa N, Walsh E, Bryant V, et al. The effect of noninvasive ventilation on ALS patients and their caregivers. Neurology. 2006;66(8):1211–1217.
  • Bourke SC, Tomlinson M, Williams TL, Bullock RE, Shaw PJ, Gibson GJ. Effects of non-invasive ventilation on survival and quality of life in patients with amyotrophic lateral sclerosis: a randomised controlled trial. Lancet Neurol. 2006;5(2):140–147.
  • Lo Coco D, Marchese S, Pesco MC, La Bella V, Piccoli F, Lo Coco A. Noninvasive positive-pressure ventilation in ALS: predictors of tolerance and survival. Neurology. 2006;67(5):761–765.
  • Sancho J, Servera E, Morelot-Panzini C, Salachas F, Similowski T, Gonzalez-Bermejo J. Non-invasive ventilation effectiveness and the effect of ventilatory mode on survival in ALS patients. Amyotroph Lateral Scler Frontotemporal Degener. 2014;15(1–2):55–61.
  • Onders RP, Elmo M, Kaplan C, Katirji B, Schilz R. Final analysis of the pilot trial of diaphragm pacing in amyotrophic lateral sclerosis with long-term follow-up: diaphragm pacing positively affects diaphragm respiration. Am J Surg. 2014;207(3):393–397. [discussion 397].
  • Gonzalez-Bermejo J, Morelot-Panzini C, Salachas F, et al. Diaphragm pacing improves sleep in patients with amyotrophic lateral sclerosis. Amyotroph Lateral Scler. 2012;13(1):44–54.
  • Mahajan KR, Bach JR, Saporito L, Perez N. Diaphragm pacing and noninvasive respiratory management of amyotrophic lateral sclerosis/motor neuron disease. Muscle Nerve. 2012;46(6):851–855.
  • McDermott CJ, Maguire C, Cooper CL, et al. Protocol for diaphragm pacing in patients with respiratory muscle weakness due to motor neurone disease (DiPALS): a randomised controlled trial. BMC Neurol. 2012;12:74.
  • Hayashi H, Oppenheimer EA. ALS patients on TPPV: totally locked-in state, neurologic findings and ethical implications. Neurology. 2003;61(1):135–137.
  • Sanjuan-Lopez P, Valino-Lopez P, Ricoy-Gabaldon J, Verea- Hernando H. Amyotrophic lateral sclerosis: impact of pulmonary follow-up and mechanical ventilation on survival. A study of 114 cases. Arch Bronconeumol. 2014;50(12):509–513.
  • Clemens KE, Klaschik E. Morphine in the management of dyspnoea in ALS. A pilot study. Eur J Neurol. 2008;15(5):445–450.
  • Young CA, Ellis C, Johnson J, Sathasivam S, Pih N. Treatment for sialorrhea (excessive saliva) in people with motor neuron disease/amyotrophic lateral sclerosis. Cochrane Database Syst Rev. 2011;5:CD006981.
  • Banfi P, Ticozzi N, Lax A, Guidugli GA, Nicolini A, Silani V. A review of options for treating sialorrhea in amyotrophic lateral sclerosis. Respir Care. Epub September 16, 2014.
  • Jackson CE, Gronseth G, Rosenfeld J, et al; Muscle Study Group. Randomized double-blind study of botulinum toxin type B for sialorrhea in ALS patients. Muscle Nerve. 2009;39(2):137–143.
  • Verma A, Steele J. Botulinum toxin improves sialorrhea and quality of living in bulbar amyotrophic lateral sclerosis. Muscle Nerve. 2006;34(2):235–237.
  • Assouline A, Levy A, Abdelnour-Mallet M, et al. Radiation therapy for hypersalivation: a prospective study in 50 amyotrophic lateral sclerosis patients. Int J Radiat Oncol Biol Phys. 2014;88(3):589–595.
  • Mustfa N, Aiello M, Lyall RA, et al. Cough augmentation in amyotrophic lateral sclerosis. Neurology. 2003;61(9):1285–1287.
  • Vitacca M, Paneroni M, Trainini D, et al. At home and on demand mechanical cough assistance program for patients with amyotrophic lateral sclerosis. Am J Phys Med Rehabil. 2010;89(5):401–406.
  • Körner S, Sieniawski M, Kollewe K, et al. Speech therapy and communication device: impact on quality of life and mood in patients with amyotrophic lateral sclerosis. Amyotroph Lateral Scler Frontotemporal Degener. 2013;14(1):20–25.
  • Kasarskis EJ, Scarlata D, Hill R, Fuller C, Stambler N, Cedarbaum JM. A retrospective study of percutaneous endoscopic gastrostomy in ALS patients during the BDNF and CNTF trials. J Neurol Sci. 1999;169(1–2):118–125.
  • Desport JC, Preux PM, Truong TC, Vallat JM, Sautereau D, Couratier P. Nutritional status is a prognostic factor for survival in ALS patients. Neurology. 1999;53(5):1059–1063.
  • Katzberg HD, Benatar M. Enteral tube feeding for amyotrophic lateral sclerosis/motor neuron disease. Cochrane Database Syst Rev. 2011;1:CD004030.
  • Bello-Haas VD, Florence JM, Kloos AD, et al. A randomized controlled trial of resistance exercise in individuals with ALS. Neurology. 2007;68(23):2003–2007.
  • Baldinger R, Katzberg HD, Weber M. Treatment for cramps in amyotrophic lateral sclerosis/motor neuron disease. Cochrane Database Syst Rev. 2012;4:CD004157.
  • Chou R, Peterson K, Helfand M. Comparative efficacy and safety of skeletal muscle relaxants for spasticity and musculoskeletal conditions: a systematic review. J Pain Symptom Manage. 2004;28(2):140–175.
  • McDonald ER, Wiedenfeld SA, Hillel A, Carpenter CL, Walter RA. Survival in amyotrophic lateral sclerosis. The role of psychological factors. Arch Neurol. 1994;51(1):17–23.
  • Carter GT, Weiss MD, Lou JS, et al. Modafinil to treat fatigue in amyotrophic lateral sclerosis: an open label pilot study. Am J Hosp Palliat Care. 2005;22(1):55–59.
  • Rabkin JG, Gordon PH, McElhiney M, Rabkin R, Chew S, Mitsumoto H. Modafinil treatment of fatigue in patients with ALS: a placebo-controlled study. Muscle Nerve. 2009;39(3):297–303.
  • Pioro EP, Brooks BR, Cummings J, et al; Safety, Tolerability, and Efficacy Results Trial of AVP-923 in PBA Investigators. Dextromethorphan plus ultra low-dose quinidine reduces pseudobulbar affect. Ann Neurol. 2010;68(5):693–702.
  • Meissner F, Molawi K, Zychlinsky A. Mutant superoxide dismutase 1-induced IL-1beta accelerates ALS pathogenesis. Proc Natl Acad Sci U S A. 2010;107(29):13046–13050.
  • Kalmar B, Edet-Amana E, Greensmith L. Treatment with a coinducer of the heat shock response delays muscle denervation in the SOD1-G93A mouse model of amyotrophic lateral sclerosis. Amyotroph Lateral Scler. 2012;13(4):378–392.
  • Kalmar B, Novoselov S, Gray A, Cheetham ME, Margulis B, Greensmith L. Late stage treatment with arimoclomol delays disease progression and prevents protein aggregation in the SOD1 mouse model of ALS. J Neurochem. 2008;107(2):339–350.
  • Cudkowicz ME, Shefner JM, Simpson E, et al; Northeast ALS Consortium. Arimoclomol at dosages up to 300 mg/day is well tolerated and safe in amyotrophic lateral sclerosis. Muscle Nerve. 2008;38(1):837–844.
  • Yan Q, Elliott J, Snider WD. Brain-derived neurotrophic factor rescues spinal motor neurons from axotomy-induced cell death. Nature. 1992;360(6406):753–755.
  • Novikov L, Novikova L, Kellerth JO. Brain-derived neurotrophic factor promotes survival and blocks nitric oxide synthase expression in adult rat spinal motoneurons after ventral root avulsion. Neurosci Lett. 1995;200(1):45–48.
  • Ikeda K, Klinkosz B, Greene T, et al. Effects of brain-derived neurotrophic factor on motor dysfunction in wobbler mouse motor neuron disease. Ann Neurol. 1995;37(4):505–511.
  • Bemelmans AP, Husson I, Jaquet M, Mallet J, Kosofsky BE, Gressens P. Lentiviral-mediated gene transfer of brain-derived neurotrophic factor is neuroprotective in a mouse model of neonatal excitotoxic challenge. J Neurosci Res. 2006;83(1):50–60.
  • A controlled trial of recombinant methionyl human BDNF in ALS: the BDNF Study Group (phase III). Neurology. 1999;52(7):1427–1433.
  • Sendtner M, Kreutzberg GW, Thoenen H. Ciliary neurotrophic factor prevents the degeneration of motor neurons after axotomy. Nature. 1990;345(6274):440–441.
  • Bongioanni P, Reali C, Sogos V. Ciliary neurotrophic factor (CNTF) for amyotrophic lateral sclerosis/motor neuron disease. Cochrane Database Syst Rev. 2004;3:CD004302.
  • Rothstein JD, Patel S, Regan MR, et al. Beta-lactam antibiotics offer neuroprotection by increasing glutamate transporter expression. Nature. 2005;433(7021):73–77.
  • Cudkowicz ME, Titus S, Kearney M, et al; Ceftriaxone Study Investigators. Safety and efficacy of ceftriaxone for amyotrophic lateral sclerosis: a multi-stage, randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2014;13(11):1083–1091.
  • Drachman DB, Frank K, Dykes-Hoberg M, et al. Cyclooxygenase 2 inhibition protects motor neurons and prolongs survival in a transgenic mouse model of ALS. Ann Neurol. 2002;52(6):771–778.
  • Cudkowicz ME, Shefner JM, Schoenfeld DA, et al. Trial of celecoxib in amyotrophic lateral sclerosis. Ann Neurol. 2006;60(1):22–31.
  • Beal MF. Coenzyme Q10 as a possible treatment for neurodegenerative diseases. Free Radic Res. 2002;36(4):455–460.
  • Kaufmann P, Thompson JL, Levy G, et al; QALS Study Group. Phase II trial of CoQ10 for ALS finds insufficient evidence to justify phase III. Ann Neurol. 2009;66(2):235–244.
  • Klivenyi P, Ferrante RJ, Matthews RT, et al. Neuroprotective effects of creatine in a transgenic animal model of amyotrophic lateral sclerosis. Nat Med. 1999;5(3):347–350.
  • Pastula DM, Moore DH, Bedlack RS. Creatine for amyotrophic lateral sclerosis/motor neuron disease. Cochrane Database Syst Rev. 2010;6:CD005225.
  • Keep M, Elmer E, Fong KS, Csiszar K. Intrathecal cyclosporin prolongs survival of late-stage ALS mice. Brain Res. 2001;894(2):327–331.
  • Appel SH, Stewart SS, Appel V, et al. A double-blind study of the effectiveness of cyclosporine in amyotrophic lateral sclerosis. Arch Neurol. 1988;45(4):381–386.
  • Vieira FG, LaDow E, Moreno A, et al. Dexpramipexole is ineffective in two models of ALS related neurodegeneration. PLoS One. 2014;9(12):e91608.
  • Cudkowicz ME, van den Berg LH, Shefner JM, et al; EMPOWER Investigators. Dexpramipexole versus placebo for patients with amyotrophic lateral sclerosis (EMPOWER): a randomised, double-blind, phase 3 trial. Lancet Neurol. 2013;12(11):1059–1067.
  • Ito H, Wate R, Zhang J, et al. Treatment with edaravone, initiated at symptom onset, slows motor decline and decreases SOD1 deposition in ALS mice. Exp Neurol. 2008;213(2):448–455.
  • Abe K, Itoyama Y, Sobue G, et al; Edaravone ALS Study Group. Confirmatory double-blind, parallel-group, placebo-controlled study of efficacy and safety of edaravone (MCI-186) in amyotrophic lateral sclerosis patients. Amyotroph Lateral Scler Frontotemporal Degener. 2014;15(7–8):610–617.
  • Taylor CP. Mechanisms of action of gabapentin. Rev Neurol. 1997;153(Suppl 1):S39–S45.
  • Gurney ME, Cutting FB, Zhai P, et al. Benefit of vitamin E, riluzole, and gabapentin in a transgenic model of familial amyotrophic lateral sclerosis. Ann Neurol. 1996;39(2):147–157.
  • Miller RG, Moore DH 2nd, Gelinas DF, et al; Western ALS Study Group. Phase III randomized trial of gabapentin in patients with amyotrophic lateral sclerosis. Neurology. 2001;56(7):843–848.
  • Angelov DN, Waibel S, Guntinas-Lichius O, et al. Therapeutic vaccine for acute and chronic motor neuron diseases: implications for amyotrophic lateral sclerosis. Proc Natl Acad Sci U S A. 2003;100(8):4790–4795.
  • Haenggeli C, Julien JP, Mosley RL, et al. Therapeutic immunization with a glatiramer acetate derivative does not alter survival in G93A and G37R SOD1 mouse models of familial ALS. Neurobiol Dis. 2007;26(1):146–152.
  • Meininger V, Drory VE, Leigh PN, Ludolph A, Robberecht W, Silani V. Glatiramer acetate has no impact on disease progression in ALS at 40 mg/day: a double-blind, randomized, multicentre, placebo-controlled trial. Amyotroph Lateral Scler. 2009;10(5–6):378–383.
  • Nagano I, Ilieva H, Shiote M, et al. Therapeutic benefit of intrathecal injection of insulin-like growth factor-1 in a mouse model of amyotrophic lateral sclerosis. J Neurol Sci. 2005;235(1–2):61–68.
  • Lai EC, Felice KJ, Festoff BW, et al. 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. 1997;49(6):1621–1630.
  • Sakowski SA, Schuyler AD, Feldman EL. Insulin-like growth factor-I for the treatment of amyotrophic lateral sclerosis. Amyotroph Lateral Scler. 2009;10(2):63–73.
  • Sorenson EJ, Windbank AJ, Mandrekar JN, et al. Subcutaneous IGF-1 is not beneficial in 2-year ALS trial. Neurology. 2008;71(22):1770–1775.
  • Meucci N, Nobile-Orazio E, Scarlato G. Intravenous immunoglobulin therapy in amyotrophic lateral sclerosis. J Neurol. 1996;243(2):117–120.
  • Casanovas A, Ribera J, Hukkanen M, Riveros-Moreno V, Esquerda JE. Prevention by lamotrigine, MK-801 and N omega-nitro-L-arginine methyl ester of motoneuron cell death after neonatal axotomy. Neuroscience. 1996;71(2):313–325.
  • Eisen A, Stewart H, Schulzer M, Cameron D. Anti-glutamate therapy in amyotrophic lateral sclerosis: a trial using lamotrigine. Can J Neurol Sci. 1993;20(4):297–301.
  • 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 Neurol Scand. 2003;108(1):1–8.
  • Fornai F, Longone P, Cafaro L, et al. Lithium delays progression of amyotrophic lateral sclerosis. Proc Natl Acad Sci U S A. 2008;105(6):2052–2057.
  • Miller RG, Moore DH, Forshew DA, et al; WALS Study Group. Phase II screening trial of lithium carbonate in amyotrophic lateral sclerosis: examining a more efficient trial design. Neurology. 2011;77(10):973–979.
  • UKMND-LiCALS Study Group; Morrison KE, Dhariwal S, et al. Lithium in patients with amyotrophic lateral sclerosis (LiCALS): a phase 3 multicentre, randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2013;12(4):339–345.
  • Suchy J, Lee S, Ahmed A, Shea TB. Dietary supplementation with S-adenosyl methionine delays the onset of motor neuron pathology in a murine model of amyotrophic lateral sclerosis. Neuromolecular Med. 2010;12(1):86–97.
  • Orrell RW, Lane RJ, Ross M. A systematic review of antioxidant treatment for amyotrophic lateral sclerosis/motor neuron disease. Amyotroph Lateral Scler. 2008;9(4):195–211.
  • Van Den Bosch L, Tilkin P, Lemmens G, Robberecht W. Minocycline delays disease onset and mortality in a transgenic model of ALS. Neuroreport. 2002;13(8):1067–1070.
  • Gordon PH, Moore DH, Miller RG, et al; Western ALS Study Group. Efficacy of minocycline in patients with amyotrophic lateral sclerosis: a phase III randomised trial. Lancet Neurol. 2007;6(12):1045–1053.
  • Andreassen OA, Dedeoglu A, Klivenyi P, Beal MF, Bush AI. N-acetyl-L-cysteine improves survival and preserves motor performance in an animal model of familial amyotrophic lateral sclerosis. Neuroreport. 2000;11(11):2491–2493.
  • Neuraltus. The Science: Targeting Neuroinflammation to Treat Neurodegenerative Diseases; 2013. Available from: http://www.neuraltus.com/pages/science.html2013.
  • Miller RG, Zhang R, Block G, et al. NP001 regulation of macrophage activation markers in ALS: a phase I clinical and biomarker study. Amyotroph Lateral Scler Frontotemporal Degener. 2014;15(7–8):601–609.
  • Sunyach C, Michaud M, Arnoux T, et al. Olesoxime delays muscle denervation, astrogliosis, microglial activation and motoneuron death in an ALS mouse model. Neuropharmacology. 2012;62(7):2346–2352.
  • Lenglet T, Lacomblez L, Abitbol JL, et al; Mitotarget Study Group. A phase II-III trial of olesoxime in subjects with amyotrophic lateral sclerosis. Eur J Neurol. 2014;21(3):529–536.
  • Kelemen J, Hedlund W, Orlin JB, Berkman EM, Munsat TL. Plasmapheresis with immunosuppression in amyotrophic lateral sclerosis. Arch Neurol. 1983;40(12):752–753.
  • Wright PD, Huang M, Weiss A, et al. Screening for inhibitors of the SOD1 gene promoter: pyrimethamine does not reduce SOD1 levels in cell and animal models. Neurosci Lett. 2010;482(3):188–192.
  • Lange DJ, Andersen PM, Remanan R, Marklund S, Benjamin D. Pyrimethamine decreases levels of SOD1 in leukocytes and cerebrospinal fluid of ALS patients: a phase I pilot study. Amyotroph Lateral Scler Frontotemporal Degener. 2013;14(3):199–204.
  • Waibel S, Reuter A, Malessa S, Blaugrund E, Ludolph AC. Rasagiline alone and in combination with riluzole prolongs survival in an ALS mouse model. J Neurol. 2004;251(9):1080–1084.
  • Van Damme P, Leyssen M, Callewaert G, Robberecht W, Van Den Bosch L. The AMPA receptor antagonist NBQX prolongs survival in a transgenic mouse model of amyotrophic lateral sclerosis. Neurosci Lett. 2003;343(2):81–84.
  • Tortarolo M, Grignaschi G, Calvaresi N, et al. Glutamate AMPA receptors change in motor neurons of SOD1G93A transgenic mice and their inhibition by a noncompetitive antagonist ameliorates the progression of amytrophic lateral sclerosis-like disease. J Neurosci Res. 2006;83(1):134–146.
  • Paizs M, Tortarolo M, Bendotti C, Engelhardt JI, Siklos L. Talampanel reduces the level of motoneuronal calcium in transgenic mutant SOD1 mice only if applied presymptomatically. Amyotroph Lateral Scler. 2011;12(5):340–344.
  • Pascuzzi RM, Shefner J, Chappell AS, et al. A phase II trial of talampanel in subjects with amyotrophic lateral sclerosis. Amyotroph Lateral Scler. 2010;11(3):266–271.
  • Traynor BJ, Bruijn L, Conwit R, et al. Neuroprotective agents for clinical trials in ALS: a systematic assessment. Neurology. 2006;67(1):20–27.
  • Hwee DT, Kennedy A, Ryans J, et al. Fast skeletal muscle troponin activator tirasemtiv increases muscle function and performance in the B6SJL-SOD1G93A ALS mouse model. PLoS One. 2014;9(5):e96921.
  • Shefner JM, Watson ML, Meng L, Wolff AA; Neals/Cytokinetics STUDY Team. A study to evaluate safety and tolerability of repeated doses of tirasemtiv in patients with amyotrophic lateral sclerosis. Amyotroph Lateral Scler Frontotemporal Degener. 2013;14(7–8):574–581.
  • Maragakis NJ, Jackson M, Ganel R, Rothstein JD. Topiramate protects against motor neuron degeneration in organotypic spinal cord cultures but not in G93A SOD1 transgenic mice. Neurosci Lett. 2003;338(2):107–110.
  • Cudkowicz ME, Shefner JM, Schoenfeld DA, et al; Northeast ALS Consortium. A randomized, placebo-controlled trial of topiramate in amyotrophic lateral sclerosis. Neurology. 2003;61(4):456–464.
  • Poesen K, Lambrechts D, Van Damme P, et al. Novel role for vascular endothelial growth factor (VEGF) receptor-1 and its ligand VEGF-B in motor neuron degeneration. J Neurosci. 2008;28(42):10451–10459.
  • Zheng C, Nennesmo I, Fadeel B, Henter JI. Vascular endothelial growth factor prolongs survival in a transgenic mouse model of ALS. Ann Neurol. 2004;56(4):564–567.
  • Dodge JC, Treleaven CM, Fidler JA, et al. AAV4-mediated expression of IGF-1 and VEGF within cellular components of the ventricular system improves survival outcome in familial ALS mice. Mol Ther. 2010;18(12):2075–2084.
  • Pronto-Laborinho AC, Pinto S, de Carvalho M. Roles of vascular endothelial growth factor in amyotrophic lateral sclerosis. Biomed Res Int. 2014;2014:947513.
  • 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. Amyotroph Lateral Scler Other Motor Neuron Disord. 2001;2(1):9–18.
  • Graf M, Ecker D, Horowski R, et al; German Vitamin E/ALS Study Group. High dose vitamin E therapy in amyotrophic lateral sclerosis as add-on therapy to riluzole: results of a placebo-controlled double-blind study. J Neural Transm. 2005;112(5):649–660.
  • Wang H, O’Reilly ÉJ, Weisskopf MG, et al. Vitamin E intake and risk of amyotrophic lateral sclerosis: a pooled analysis of data from 5 prospective cohort studies. Am J Epidemiol. 2011;173(6):595–602.