Early investigational drugs targeting tau protein for the treatment of Alzheimers disease

Expert Opinion on Investigational Drugs

Volumn 24, Issue 10, 2015, Pages 1355-1360

  Anand, Keshav ^a   Sabbagh, Marwan ^b  

^a BANNER GOOD SAMARITAN MEDICAL CENTER   (United States)

^b SUN HEALTH RESEARCH INSTITUTE   (United States)

Author keywords

Alzheimers; clinical trial; dementia; drug development; tau

Indexed keywords

1,3,4 OXADIAZOLE DERIVATIVE; 2 METHYL 5 (3 [4 [METHYLSULFINYL]PHENYL] 1 BENZOFURAN 5 YL)1,3,4 OXADIAZOLE; AADVAC 1; ACL 35; ALZHEIMER DISEASE VACCINE; BMS 986168; BUTYLPHTHALIDE; CENTRAL NERVOUS SYSTEM AGENTS; DAVUNETIDE; EPOTHILONE D; HUMAN MONOCLONAL ANTIBODY; LITHIUM; PROTEIN INHIBITOR; PROTEIN KINASE INHIBITOR; RG 7345; TAU AGGREGATION INHIBITOR; TAU PROTEIN; TIDEGLUSIB; TPI 287; UNCLASSIFIED DRUG; VALPROIC ACID; NEW DRUG;

ACTIVE IMMUNIZATION; ALZHEIMER DISEASE; COGNITION; DRUG TARGETING; HUMAN; IMMUNOTHERAPY; IN VITRO STUDY; IN VIVO STUDY; NONHUMAN; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; TRANSGENIC MOUSE; ANIMAL; DISEASE COURSE; DRUG DESIGN; METABOLISM; MOLECULARLY TARGETED THERAPY; PATHOPHYSIOLOGY; PROCEDURES;

ALZHEIMER DISEASE; ANIMALS; DISEASE PROGRESSION; DRUG DESIGN; DRUGS, INVESTIGATIONAL; HUMANS; IMMUNOTHERAPY; MOLECULAR TARGETED THERAPY; TAU PROTEINS;

EID: 84941600642     PISSN: 13543784     EISSN: 17447658     Source Type: Journal    
DOI: 10.1517/13543784.2015.1075002     Document Type: Review

References (35)

1. Querfurth HW, LaFerla FM. Alzheimers disease. N Engl J Med 2010; 362 (4): 329-44
2. Berk C, Paul G, Sabbagh M. Investigational drugs in Alzheimers disease: current progress. Expert Opin Investig Drugs 2014; 23 (6): 837-46
3. Grundke-Iqbal I, Iqbal K, Tung YC, et al. Abnormal phosphorylation of the microtubule-associated protein tau (tau) in Alzheimer cytoskeletal pathology. Proc Natl Acad Sci U S A 1986; 83 (13): 4913-17
4. Williams DR. Tauopathies: classification and clinical update on neurodegenerative diseases associated with microtubule-associated protein tau. Intern Med J 2006; 36 (10): 652-60
5. Boutajangout A, Wisniewski T. Tau-based therapeutic approaches for Alzheimers disease-a mini-review. Gerontology 2014; 60 (5): 381-5
6. Giacobini E, Gold G. Alzheimer disease therapy - moving from amyloid-β to tau. Nat Rev Neurol 2013; 9 (12): 677-86
7. Kontsekova E, Zilka N, Kovacech B, et al. First-in-man tau vaccine targeting structural determinants essential for pathological tau-tau interaction reduces tau oligomerisation and neurofibrillary degeneration in an Alzheimers disease model. Alzheimers Res Ther 2014; 6 (4): 44
8. Theunis C, Crespo-Biel N, Gafner V, et al. Efficacy and safety of a liposome-based vaccine against protein Tau, assessed in tau.P301L mice that model tauopathy. PLoS One 2013; 8 (8): e72301
9. Bristol-Myers Squibb. A randomized, double-blind, placebo-controlled, single ascending dose study of intravenously administered BMS-986168 in healthy Subjects. In: ClinicalTrials.gov [Internet] National Library of Medicine (US). Bethesda, MD. 2000. Available from: https://clinicaltrials.gov/ct2/show/NCT02294851. NLM Identifier: NCT02294851. [Last accessed 18 May 2015]
10. Bright J, Hussain S, Dang V, et al. Human secreted tau increases amyloid-beta production. Neurobiol Aging 2015; 36 (2): 693-709
11. Troquier L, Caillierez R, Burnouf S, et al. Targeting phospho-Ser422 by active Tau Immunotherapy in the THYTau22 mouse model: a suitable therapeutic approach. Curr Alzheimer Res 2012; 9 (4): 397-405
12. Collin L, Bohrmann B, Göpfert U, et al. Neuronal uptake of tau/pS422 antibody and reduced progression of tau pathology in a mouse model of Alzheimers disease. Brain 2014; 137 (Pt 10): 2834-46
13. Oz S, Kapitansky O, Ivashco-Pachima Y, et al. The NAP motif of activity-dependent neuroprotective protein (ADNP) regulates dendritic spines through microtubule end binding proteins. Mol Psychiatry 2014; 19: 1115-24
14. Gozes I. NAP (davunetide) provides functional and structural neuroprotection. Curr Pharm Des 2011; 17 (10): 1040-4
15. Gozes I, Schirer Y, Idan-Feldman A, et al. NAP alpha-aminoisobutyric acid (IsoNAP). J Mol Neurosci 2014; 52 (1): 1-9
16. Boxer AL, Lang AE, Grossman M, et al. Davunetide in patients with progressive supranuclear palsy: a randomised, double-blind, placebo-controlled phase 2/3 trial. Lancet Neurol 2014; 13: 676-85
17. Gozes I, Iram T, Maryanovsky E, et al. Novel tubulin and tau neuroprotective fragments sharing structural similarities with the drug candidate NAP (Davuentide). J Alzheimers Dis 2014; 40 (Suppl 1): S23-36
18. Gozes I. The cytoskeleton as a drug target for neuroprotection: the case of the autism- mutated ADNP. Biol Chem 2015. [Epub ahead of print]
19. Brunden KR, Zhang B, Carroll J, et al. Epothilone D improves microtubule density, axonal integrity, and cognition in a transgenic mouse model of tauopathy. J Neurosci 2010; 30 (41): 13861-6
20. Zhang B, Carroll J, Trojanowski JQ, et al. The microtubule-stabilizing agent, epothilone D, reduces axonal dysfunction, neurotoxicity, cognitive deficits, and Alzheimer-like pathology in an interventional study with aged tau transgenic mice. J Neurosci 2012; 32 (11): 3601-11
21. Bristol-Myers Squibb. Study to Evaluate the Safety, Tolerability and the Effect of BMS-241027 on Cerebrospinal Fluid Biomarkers in Subjects With Mild Alzheimers Disease. In: ClinicalTrials.gov. Internet National Library of Medicine (US), Bethesda, MD; 2000. Available from: https://www.clinicaltrials.gov/ct/show/NCT01492374. Identifier: NCT01492374. [Last accessed 23 May 2015]
22. Cortice biosciences announces results from studies evaluating pipeline candidates TPI 287 and CRT 001 in preclinical models of tauopathies and Alzheimers disease. 2014. Available from: http://globenewswire.com/news-release/2014/11/12/682514/10107850/en/Cortice-Biosciences-Announces-Results-From-Studies-Evaluating-Pipeline-Candidates-TPI-287-and-CRT-001-in-Preclinical-Models-of-Tauopathies-and-Alzheimer-s-Disease.html. [Last accessed 23 May 2015]
23. Wischik CM, Harrington CR, Storey JMD. Tau-aggregation inhibitor therapy for Alzheimers disease. Biochem Pharmacol 2014; 88 (4): 529-39
24. Wischik CM, Staff RT, Wischik DJ, et al. Tau aggregation inhibitor therapy: an exploratory phase 2 study in mild or moderate Alzheimers disease. J Alzheimers Dis 2015; 44 (2): 705-20
25. Del Ser T, Steinwachs KC, Gertz HJ, et al. Treatment of Alzheimers disease with the GSK-3 inhibitor tideglusib: a pilot study. J Alzheimers Dis 2013; 33 (1): 205-15
26. Lovestone S, Boada M, Dubois B, et al. A phase II trial of tideglusib in Alzheimers disease. J Alzheimers Dis 2015; 45 (1): 75-88
27. Forlenza OV, Diniz BS, Radanovic M, et al. Disease-modifying properties of long-term lithium treatment for amnestic mild cognitive impairment: randomised controlled trial. Br J Psychiatry 2011; 198 (5): 351-6
28. Forlenza OV, Coutinho AMN, Aprahamian I, et al. Long-Term Lithium treatment reduces glucose metabolism in the cerebellum and hippocampus of nondemented older adults: an [(18)F]FDG-PET study. ACS Chem Neurosci 2014; 5 (6): 484-9
29. Forlenza OV, de Paula VJ, Machado-Vieira R, et al. Does lithium prevent Alzheimers disease? Drugs Aging 2012; 29 (5): 335-42
30. Forlenza OV, De-Paula VJR, Diniz BSO. Neuroprotective effects of lithium: implications for the treatment of Alzheimers disease and related neurodegenerative disorders. ACS Chem Neurosci 2014; 5 (6): 443-50
31. Hu JP, Xie JW, Wang CY, et al. Valproate reduces tau phosphorylation via cyclin-dependent kinase 5 and glycogen synthase kinase 3 signaling pathways. Brain Res Bull 2011; 85 (3-4): 194-200
32. Tariot PN, Schneider LS, Cummings J, et al. Chronic divalproex sodium to attenuate agitation and clinical progression of Alzheimer disease. Arch Gen Psychiatry 2011; 68 (8): 853-61
33. Fleisher AS, Truran D, Mai JT, et al. Chronic divalproex sodium use and brain atrophy in Alzheimer disease. Neurology 2011; 77 (13): 1263-71
34. Peng Y, Hu Y, Xu S, et al. L-3-n-butylphthalide reduces tau phosphorylation and improves cognitive deficits in AβPP/PS1-Alzheimers transgenic mice. J Alzheimers Dis 2012; 29 (2): 379-91
35. Onishi T, Iwashita H, Uno Y, et al. A novel glycogen synthase kinase-3 inhibitor 2-methyl-5-(3-{4-[(S)-methylsulfinyl]phenyl}-1-benzofuran-5-yl)-1,3,4-oxadiazole decreases tau phosphorylation and ameliorates cognitive deficits in a transgenic model of Alzheimers disease. J Neurochem 2011; 119 (6): 1330-40