1,536
Views
22
CrossRef citations to date
0
Altmetric
Review

Drugs in clinical development for the treatment of amyotrophic lateral sclerosis

, , &
Pages 403-414 | Received 16 Dec 2016, Accepted 01 Mar 2017, Published online: 14 Mar 2017

References

  • Talbott EO, Malek AM, Lacomis D. The epidemiology of amyotrophic lateral sclerosis. Handb Clin Neurol. 2016;138:225–238.
  • Zarei S, Carr K, Reiley L, et al. A comprehensive review of amyotrophic lateral sclerosis. Surg Neurol Int. 2015;6:171.
  • Zufiria M, Gil-Bea FJ, Fernandez-Torron R, et al. ALS: a bucket of genes, environment, metabolism and unknown ingredients. Prog Neurobiol. 2016;142:104–129.
  • Mathis S, Couratier P, Julian A, et al. Management and therapeutic perspectives in amyotrophic lateral sclerosis. Expert Rev Neurother. 2017;17:263–276.
  • Miller RG, Mitchell JD, Moore DH. Riluzole for amyotrophic lateral sclerosis (ALS)/motor neuron disease (MND). Cochrane Database Syst Rev. 2012;(3):Cd001447.
  • Cheramy A, Barbeito L, Godeheu G, et al. Riluzole inhibits the release of glutamate in the caudate nucleus of the cat in vivo. Neurosci Lett. 1992;147:209–212.
  • Ittner LM, Halliday GM, Kril JJ, et al. FTD and ALS–translating mouse studies into clinical trials. Nat Reviews Neurol. 2015;11:360–366.
  • Nicholson KA, Cudkowicz ME, Berry JD. Clinical trial designs in amyotrophic lateral sclerosis: does one design fit all? Neurotherapeutics. 2015;12:376–383.
  • Harikrishnareddy D, Misra S, Upadhyay S, et al. Roots to start research in amyotrophic lateral sclerosis: molecular pathways and novel therapeutics for future. Rev Neurosci. 2015;26:161–181.
  • Kumar V, Islam A, Hassan MI, et al. Therapeutic progress in amyotrophic lateral sclerosis-beginning to learning. Eur J Med Chem. 2016;121:903–917.
  • Mitchell JD, Callagher P, Gardham J, et al. Timelines in the diagnostic evaluation of people with suspected amyotrophic lateral sclerosis (ALS)/motor neuron disease (MND) – a 20-year review: can we do better? Amyotroph Lateral Scler. 2010;11:537–541.
  • Biomarkers definition working group (Bethesda, USA). Biomarkers and surrogate endpoints: preferred definitions and conceptual framework. Clin Pharmacol Ther. 2001;69:89–95.
  • Benatar M, Boylan K, Jeromin A, et al. ALS biomarkers for therapy development: state of the field and future directions. Muscle Nerve. 2016;53:169–182.
  • Fan Z, Calsolaro V, Atkinson RA, et al. Flutriciclamide (18F-GE180) PET: first-in-human PET study of novel third-generation in vivo marker of human translocator protein. J Nucl Med. 2016;57:1753–1759.
  • Kim T, Pae AN. Translocator protein (TSPO) ligands for the diagnosis or treatment of neurodegenerative diseases: a patent review (2010-2015; part 2). Expert Opin Ther Pat. 2016;26:1353–1366.
  • Liu B, Le KX, Park MA, et al. In vivo detection of age- and disease-related increases in neuroinflammation by 18F-GE180 TSPO MicroPET imaging in wild-type and Alzheimer’s transgenic mice. J Neurosci. 2015;35:15716–15730.
  • Grossman M, Elman L, McCluskey L, et al. Phosphorylated tau as a candidate biomarker for amyotrophic lateral sclerosis. JAMA Neurol. 2014;71:442–448.
  • Harada R, Okamura N, Furumoto S, et al. Characteristics of Tau and its ligands in PET imaging. Biomolecules. 2016;6:7.
  • Eisele P, Konstandin S, Griebe M, et al. Heterogeneity of acute multiple sclerosis lesions on sodium (23Na) MRI. Mult Scler. 2016;22:1040–1047.
  • Mellon EA, Pilkinton DT, Clark CM, et al. Sodium MR imaging detection of mild Alzheimer disease: preliminary study. AJNR Am J Neuroradiol. 2009;30:978–984.
  • Reetz K, Romanzetti S, Dogan I, et al. Increased brain tissue sodium concentration in Huntington’s disease – a sodium imaging study at 4 T. Neuroimage. 2012;63:517–524.
  • Aebischer J, Moumen A, Sazdovitch V, et al. Elevated levels of IFNgamma and LIGHT in the spinal cord of patients with sporadic amyotrophic lateral sclerosis. Eur J Neurol. 2012;19(752–9):e45–6.
  • Liu J, Gao L, Zang D. Elevated levels of IFN-gamma in CSF and serum of patients with amyotrophic lateral sclerosis. Plos One. 2015;10:e0136937.
  • Srivastava AK, Bulte JW. Seeing stem cells at work in vivo. Stem Cell Rev. 2014;10:127–144.
  • Mao Z, Zhang S, Chen H. Stem cell therapy for amyotrophic lateral sclerosis. Cell Regen. 2015;4:11.
  • Ferrero I, Mazzini L, Rustichelli D, et al. Bone marrow mesenchymal stem cells from healthy donors and sporadic amyotrophic lateral sclerosis patients. Cell Transplant. 2008;17:255–266.
  • 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;30:1277–1285.
  • Deda H, Inci MC, Kurekci 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;11:18–25.
  • Mazzini L, Fagioli F, Boccaletti R, et al. Stem cell therapy in amyotrophic lateral sclerosis: a methodological approach in humans. Amyotroph Lateral Scler Other Motor Neuron Disord. 2009;4:158-161.
  • Oh KW, Moon C, Kim HY, et al. Phase I trial of repeated intrathecal autologous bone marrow-derived mesenchymal stromal cells in amyotrophic lateral sclerosis. Stem Cells Transl Med. 2015;4:590–597.
  • Lepore AC, O’Donnell J, Kim AS, et al. Human glial-restricted progenitor transplantation into cervical spinal cord of the SOD1 mouse model of ALS. Plos One. 2011;6:e25968.
  • Atassi N, Beghi E, Blanquer M, et al. Intraspinal stem cell transplantation for amyotrophic lateral sclerosis: ready for efficacy clinical trials? Cytotherapy. 2016;18:1471–1475.
  • Petrou P, Gothelf Y, Argov Z, et al. Safety and clinical effects of mesenchymal stem cells secreting neurotrophic factor transplantation in patients with amyotrophic lateral sclerosis: results of phase 1/2 and 2a clinical trials. JAMA Neurol. 2016;73:337–344.
  • Smith RA, Miller TM, Yamanaka K, et al. Antisense oligonucleotide therapy for neurodegenerative disease. J Clin Invest. 2006;116:2290–2296.
  • 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;12:435–442.
  • Oldfield V, Dhillon S, Plosker GL. Tocilizumab: a review of its use in the management of rheumatoid arthritis. Drugs. 2009;69:609–632.
  • Teng FY, Tang BL. Nogo-A and Nogo-66 receptor in amyotrophic lateral sclerosis. J Cell Mol Med. 2008;12:1199–1204.
  • Bros-Facer V, Krull D, Taylor A, et al. Treatment with an antibody directed against Nogo-A delays disease progression in the SOD1G93A mouse model of amyotrophic lateral sclerosis. Hum Mol Genet. 2014;23:4187–4200.
  • Meininger V, Pradat PF, Corse A, et al. Safety, pharmacokinetic, and functional effects of the Nogo-A monoclonal antibody in amyotrophic lateral sclerosis: a randomized, first-in-human clinical trial. Plos One. 2014;9:e97803.
  • McCormick AL, Brown RH Jr., Cudkowicz ME, et al. Quantification of reverse transcriptase in ALS and elimination of a novel retroviral candidate. Neurology. 2008;70:278–283.
  • Douville R, Liu J, Rothstein J, et al. Identification of active loci of a human endogenous retrovirus in neurons of patients with amyotrophic lateral sclerosis. Ann Neurol. 2011;69:141–151.
  • Christensen T. Human endogenous retroviruses in neurologic disease. Apmis. 2016;124:116–126.
  • Li W, Lee MH, Henderson L, et al. Human endogenous retrovirus-K contributes to motor neuron disease. Sci Transl Med. 2015;7:307ra153.
  • Mizuno T, Kurotani T, Komatsu Y, et al. Neuroprotective role of phosphodiesterase inhibitor ibudilast on neuronal cell death induced by activated microglia. Neuropharmacology. 2004;46:404–411.
  • Goodman A. Tamoxifen, a cancer therapy, explored for ALS. Neurol Today. 2005;5:22–26.
  • Zou W, Fang C, Ji X, et al. Estrogen receptor (ER)-alpha36 is involved in estrogen- and tamoxifen-induced neuroprotective effects in ischemic stroke models. Plos One. 2015;10:e0140660.
  • Hu JH, Zhang H, Wagey R, et al. Protein kinase and protein phosphatase expression in amyotrophic lateral sclerosis spinal cord. J Neurochem. 2003;85:432–442.
  • Wang IF, Guo BS, Liu YC, et al. Autophagy activators rescue and alleviate pathogenesis of a mouse model with proteinopathies of the TAR DNA-binding protein 43. Proc Natl Acad Sci U S A. 2012;109:15024–15029.
  • Noto Y, Shibuya K, Vucic S, et al. Novel therapies in development that inhibit motor neuron hyperexcitability in amyotrophic lateral sclerosis. Expert Rev Neurother. 2016;16:1147–1154.
  • Weiss MD, Macklin EA, Simmons Z, et al. A randomized trial of mexiletine in ALS: safety and effects on muscle cramps and progression. Neurology. 2016;86:1474–1481.
  • Rudzinski LA, Velez-Ruiz NJ, Gedzelman ER, et al. New antiepileptic drugs: focus on ezogabine, clobazam, and perampanel. J Investig Med. 2016;64:1087–1101.
  • Wainger BJ, Kiskinis E, Mellin C, et al. Intrinsic membrane hyperexcitability of amyotrophic lateral sclerosis patient-derived motor neurons. Cell Rep. 2014;7:1–11.
  • de Carvalho M, Pinto S, Costa J, et al. A randomized, placebo-controlled trial of memantine for functional disability in amyotrophic lateral sclerosis. Amyotroph Lateral Scler. 2010;11:456–460.
  • Levine TD, Bowser R, Hank N, et al. A pilot trial of memantine and riluzole in ALS: correlation to CSF biomarkers. Amyotroph Lateral Scler. 2010;11:514–519.
  • Waibel S, Reuter A, Malessa S, et al. Rasagiline alone and in combination with riluzole prolongs survival in an ALS mouse model. J Neurol. 2004;251:1080–1084.
  • Macchi Z, Wang Y, Moore D, et al. A multi-center screening trial of rasagiline in patients with amyotrophic lateral sclerosis: possible mitochondrial biomarker target engagement. Amyotroph Lateral Scler Frontotemporal Degener. 2015;16:345–352.
  • Li Z, Lin H, Gu L, et al. Herba Cistanche (Rou Cong-Rong): one of the best pharmaceutical gifts of traditional Chinese medicine. Front Pharmacol. 2016;7:41.
  • Guo Q, Zhou Y, Wang CJ, et al. An open-label, nonplacebo-controlled study on Cistanche tubulosa glycoside capsules (Memoregain((R))) for treating moderate Alzheimer’s disease. Am J Alzheimers Dis Other Demen. 2013;28:363–370.
  • Trias E, Ibarburu S, Barreto-Nunez R, et al. Post-paralysis tyrosine kinase inhibition with masitinib abrogates neuroinflammation and slows disease progression in inherited amyotrophic lateral sclerosis. J Neuroinflammation. 2016;13:177.
  • Izumi Y, Kaji R. [Clinical trials of ultra-high-dose methylcobalamin in ALS]. Brain Nerve. 2007;59:1141–1147.
  • Kaji R, Kuzuhara S, Iwasaki Y, et al. Ultra-high dose methylcobalamin (E0302) prolongs survival of ALS: report of 7 years’ randomised double-blind, phase 3 clinical trial (ClinicalTrials.gov NCT00444613) (P7.060). 67th Meeting of the American Academy of Neurology, Washington DC, April 2015.
  • Ikeda K, Iwasaki Y, Kaji R. Neuroprotective effect of ultra-high dose methylcobalamin in wobbler mouse model of amyotrophic lateral sclerosis. J Neurol Sci. 2015;354:70–74.
  • Yoshida H, Yanai H, Namiki Y, et al. Neuroprotective effects of edaravone: a novel free radical scavenger in cerebrovascular injury. CNS Drug Rev. 2006;12:9–20.
  • 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;213:448–455.
  • DeLoach A, Cozart M, Kiaei A, et al. A retrospective review of the progress in amyotrophic lateral sclerosis drug discovery over the last decade and a look at the latest strategies. Expert Opin Drug Discov. 2015;10:1099–1118.
  • Bucchia M, Ramirez A, Parente V, et al. Therapeutic development in amyotrophic lateral sclerosis. Clin Ther. 2015;37:668–680.
  • Farah CS, Reinach FC. The troponin complex and regulation of muscle contraction. Faseb J. 1995;9:755–767.
  • Russell AJ, Hartman JJ, Hinken AC, et al. Activation of fast skeletal muscle troponin as a potential therapeutic approach for treating neuromuscular diseases. Nat Med. 2012;18:452–455.
  • 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:e96921.
  • Shefner JM, Watson ML, Meng L, et al. A study to evaluate safety and tolerability of repeated doses of tirasemtiv in patients with amyotrophic lateral sclerosis. Amyotroph Lateral Scler Frontotemporal Degener. 2013;14:574–581.
  • Hansen R, Saikali KG, Chou W, et al. Tirasemtiv amplifies skeletal muscle response to nerve activation in humans. Muscle Nerve. 2014;50:925–931.
  • Kurthy M, Mogyorosi T, Nagy K, et al. Effect of BRX-220 against peripheral neuropathy and insulin resistance in diabetic rat models. Ann N Y Acad Sci. 2002;967:482–489.
  • Kalmar B, Lu CH, Greensmith L. The role of heat shock proteins in amyotrophic lateral sclerosis: the therapeutic potential of arimoclomol. Pharmacol Ther. 2014;141:40–54.
  • 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;13:378–392.
  • Cudkowicz ME, Shefner JM, Simpson E, et al. Arimoclomol at dosages up to 300 mg/day is well tolerated and safe in amyotrophic lateral sclerosis. Muscle Nerve. 2008;38:837–844.
  • Khasnavis S, Jana A, Roy A, et al. Suppression of nuclear factor-kappaB activation and inflammation in microglia by physically modified saline. J Biol Chem. 2012;287:29529–29542.
  • Khasnavis S, Roy A, Ghosh S, et al. Protection of dopaminergic neurons in a mouse model of Parkinson’s disease by a physically-modified saline containing charge-stabilized nanobubbles. J Neuroimmune Pharmacol. 2014;9:218–232.
  • Modi KK, Jana A, Ghosh S, et al. A physically-modified saline suppresses neuronal apoptosis, attenuates tau phosphorylation and protects memory in an animal model of Alzheimer’s disease. Plos One. 2014;9:e103606.
  • Choi S, Yu E, Kim DS, et al. RNS60, a charge-stabilized nanostructure saline alters Xenopus laevis oocyte biophysical membrane properties by enhancing mitochondrial ATP production. Physiol Rep. 2015;(3)pii:e12261.
  • Rao VT, Khan D, Jones RG, et al. Potential benefit of the charge-stabilized nanostructure saline RNS60 for myelin maintenance and repair. Sci Rep. 2016;6:30020.
  • Hilton JB, White AR, Crouch PJ. Metal-deficient SOD1 in amyotrophic lateral sclerosis. J Mol Med (Berl). 2015;93:481–487.
  • McAllum EJ, Lim NK, Hickey JL, et al. Therapeutic effects of CuII(atsm) in the SOD1-G37R mouse model of amyotrophic lateral sclerosis. Amyotroph Lateral Scler Frontotemporal Degener. 2013;14:586–590.
  • Williams JR, Trias E, Beilby PR, et al. Copper delivery to the CNS by CuATSM effectively treats motor neuron disease in SOD(G93A) mice co-expressing the copper-chaperone-for-SOD. Neurobiol Dis. 2016;89:1–9.
  • eeHilton JB, White AR, Crouch PJ. Endogenous Cu in the central nervous system fails to satiate the elevated requirement for Cu in a mutant SOD1 mouse model of ALS. Metallomics. 2016;8:1002–1011.
  • Philips T, Robberecht W. Neuroinflammation in amyotrophic lateral sclerosis: role of glial activation in motor neuron disease. Lancet Neurol. 2011;10:253–263.
  • 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;15:601–609.
  • Miller RG, Block G, Katz JS, et al. Randomized phase 2 trial of NP001-a novel immune regulator: safety and early efficacy in ALS. Neurol Neuroimmunol Neuroinflamm. 2015;2:e100.
  • Patel S, Cohen F, Dean BJ, et al. Discovery of dual leucine zipper kinase (DLK, MAP3K12) inhibitors with activity in neurodegeneration models. J Med Chem. 2015;58:401–418.
  • Abdul Wahid SF, Law ZK, Ismail NA, et al. Cell-based therapies for amyotrophic lateral sclerosis/motor neuron disease. Cochrane Database Syst Rev. 2016;11:Cd011742.
  • Philips T, Rothstein JD. Rodent models of amyotrophic lateral sclerosis. Curr Protoc Pharmacol. 2015;69:5.67.1-21.
  • Liu YC, Chiang PM, Tsai KJ. Disease animal models of TDP-43 proteinopathy and their pre-clinical applications. Int J Mol Sci. 2013;14:20079–20111.
  • Sances S, Bruijn LI, Chandran S, et al. Modeling ALS with motor neurons derived from human induced pluripotent stem cells. Nat Neurosci. 2016;19:542–553.
  • Volonte C, Apolloni S, Parisi C. MicroRNAs: newcomers into the ALS picture. CNS Neurol Disord Drug Targets. 2015;14:194–207.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.