Tau-targeting antisense oligonucleotide MAPT

Humans tau Proteins / genetics Alzheimer Disease / drug therapy Oligonucleotides, Antisense / therapeutic use Treatment Outcome Double-Blind Method

Journal

Nature medicine

ISSN: 1546-170X

Titre abrégé: Nat Med

Pays: United States

ID NLM: 9502015

Informations de publication

Date de publication:
Jun 2023

Historique:

received: 01 09 2022

accepted: 29 03 2023

medline: 26 6 2023

pubmed: 25 4 2023

entrez: 24 04 2023

Statut: ppublish

Résumé

Tau plays a key role in Alzheimer's disease (AD) pathophysiology, and accumulating evidence suggests that lowering tau may reduce this pathology. We sought to inhibit MAPT expression with a tau-targeting antisense oligonucleotide (MAPT

Identifiants

DOI: 10.1038/s41591-023-02326-3 PMID: 37095250 PMC: PMC10287562

pubmed: 37095250

doi: 10.1038/s41591-023-02326-3

pii: 10.1038/s41591-023-02326-3

pmc: PMC10287562

doi:

Substances chimiques

tau Proteins 0

Oligonucleotides, Antisense 0

MAPT protein, human 0

Banques de données

ClinicalTrials.gov

['NCT03186989']

Types de publication

Randomized Controlled Trial Clinical Trial, Phase I Journal Article

Langues

eng

Sous-ensembles de citation

Pagination

1437-1447

Commentaires et corrections

Type : ErratumIn

Informations de copyright

Références

Lane, C. A., Hardy, J. & Schott, J. M. Alzheimer’s disease. Eur. J. Neurol. 25, 59–70 (2018).

pubmed: 28872215 doi: 10.1111/ene.13439

2021 Alzheimer’s disease facts and figures. Alzheimers Dement. 17, 327–406 (2021).

2020 Alzheimer’s disease facts and figures. Alzheimers Dement. https://doi.org/10.1002/alz.12068 (2020).

McKhann, G. M. et al. The diagnosis of dementia due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement. 7, 263–269 (2011).

pubmed: 21514250 pmcid: 3312024 doi: 10.1016/j.jalz.2011.03.005

Shaw, L. M. et al. Appropriate use criteria for lumbar puncture and cerebrospinal fluid testing in the diagnosis of Alzheimer’s disease. Alzheimers Dement. 14, 1505–1521 (2018).

pubmed: 30316776 pmcid: 10013957 doi: 10.1016/j.jalz.2018.07.220

Jack, C. R. Jr. et al. NIA-AA Research Framework: toward a biological definition of Alzheimer’s disease. Alzheimers Dement. 14, 535–562 (2018).

pubmed: 29653606 pmcid: 5958625 doi: 10.1016/j.jalz.2018.02.018

Braak, H., Thal, D. R., Ghebremedhin, E. & Del Tredici, K. Stages of the pathologic process in Alzheimer disease: age categories from 1 to 100 years. J. Neuropathol. Exp. Neurol. 70, 960–969 (2011).

pubmed: 22002422 doi: 10.1097/NEN.0b013e318232a379

Alzheimer’s Disease International, G.M., Prince M, Prina M. Numbers of people with dementia worldwide. An update to the estimates in the World Alzheimer Report 2015. Alzheimer’s Disease International https://www.alzint.org/resource/numbers-of-people-with-dementia-worldwide/ (2020).

Dixit, R., Ross, J. L., Goldman, Y. E. & Holzbaur, E. L. F. Differential regulation of dynein and kinesin motor proteins by tau. Science 319, 1086–1089 (2008).

pubmed: 18202255 pmcid: 2866193 doi: 10.1126/science.1152993

Hanseeuw, B. J. et al. Association of amyloid and tau with cognition in preclinical Alzheimer disease: a longitudinal study. JAMA Neurol. 76, 915–924 (2019).

pubmed: 31157827 pmcid: 6547132 doi: 10.1001/jamaneurol.2019.1424

Xia, C. et al. Association of in vivo [18F]AV-1451 tau PET imaging results with cortical atrophy and symptoms in typical and atypical Alzheimer disease. JAMA Neurol. 74, 427–436 (2017).

pubmed: 28241163 pmcid: 5470368 doi: 10.1001/jamaneurol.2016.5755

DeVos, S. L. et al. Synaptic tau seeding precedes tau pathology in human Alzheimer’s disease brain. Front. Neurosci. 12, 267 (2018).

pubmed: 29740275 pmcid: 5928393 doi: 10.3389/fnins.2018.00267

Wu, J. W. et al. Small misfolded tau species are internalized via bulk endocytosis and anterogradely and retrogradely transported in neurons. J. Biol. Chem. 288, 1856–1870 (2013).

pubmed: 23188818 doi: 10.1074/jbc.M112.394528

Calafate, S. et al. Synaptic contacts enhance cell-to-cell tau pathology propagation. Cell Rep. 11, 1176–1183 (2015).

pubmed: 25981034 doi: 10.1016/j.celrep.2015.04.043

Takeda, S. et al. Neuronal uptake and propagation of a rare phosphorylated high-molecular-weight tau derived from Alzheimer’s disease brain. Nat. Commun. 6, 8490 (2015).

pubmed: 26458742 doi: 10.1038/ncomms9490

Shipton, O. A. et al. Tau protein is required for amyloid β-induced impairment of hippocampal long-term potentiation. J. Neurosci. 31, 1688–1692 (2011).

pubmed: 21289177 pmcid: 3836238 doi: 10.1523/JNEUROSCI.2610-10.2011

Walsh, D. M. et al. Naturally secreted oligomers of amyloid β protein potently inhibit hippocampal long-term potentiation in vivo. Nature 416, 535–539 (2002).

pubmed: 11932745 doi: 10.1038/416535a

Roberson, E. D. et al. Reducing endogenous tau ameliorates amyloid β-induced deficits in an Alzheimer’s disease mouse model. Science 316, 750–754 (2007).

pubmed: 17478722 doi: 10.1126/science.1141736

Ittner, L. M. et al. Dendritic function of tau mediates amyloid-β toxicity in Alzheimer’s disease mouse models. Cell 142, 387–397 (2010).

pubmed: 20655099 doi: 10.1016/j.cell.2010.06.036

Leroy, K. et al. Lack of tau proteins rescues neuronal cell death and decreases amyloidogenic processing of APP in APP/PS1 mice. Am. J. Pathol. 181, 1928–1940 (2012).

pubmed: 23026200 doi: 10.1016/j.ajpath.2012.08.012

DeVos, S. L. et al. Tau reduction prevents neuronal loss and reverses pathological tau deposition and seeding in mice with tauopathy. Sci. Transl. Med. 9, eaag0481 (2017).

pubmed: 28123067 pmcid: 5792300 doi: 10.1126/scitranslmed.aag0481

DeVos, S. L. et al. Antisense reduction of tau in adult mice protects against seizures. J. Neurosci. 33, 12887–12897 (2013).

pubmed: 23904623 pmcid: 3728694 doi: 10.1523/JNEUROSCI.2107-13.2013

Sud, R., Geller, E. T. & Schellenberg, G. D. Antisense-mediated exon skipping decreases tau protein expression: a potential therapy for tauopathies. Mol. Ther. Nucleic Acids 3, e180 (2014).

pubmed: 25072694 pmcid: 4121519 doi: 10.1038/mtna.2014.30

Schoch, M. K. et al. Increased 4R-tau induces pathological changes in a human-tau mouse model. Neuron 90, 941–947 (2016).

pubmed: 27210553 pmcid: 5040069 doi: 10.1016/j.neuron.2016.04.042

Vossel, K. A. et al. Tau reduction prevents Aβ-induced defects in axonal transport. Science 330, 198 (2010).

pubmed: 20829454 pmcid: 3024010 doi: 10.1126/science.1194653

Qiang, L., Yu, W., Andreadis, A., Luo, M. & Baas, P. W. Tau protects microtubules in the axon from severing by katanin. J. Neurosci. 26, 3120–3129 (2006).

pubmed: 16554463 pmcid: 6674103 doi: 10.1523/JNEUROSCI.5392-05.2006

Dawson, H. N. et al. Inhibition of neuronal maturation in primary hippocampal neurons from tau deficient mice. J. Cell Sci. 114, 1179–1187 (2001).

pubmed: 11228161 doi: 10.1242/jcs.114.6.1179

Fujio, K. et al. 14-3-3 proteins and protein phosphatases are not reduced in tau-deficient mice. NeuroReport 18, 1049–1052 (2007).

pubmed: 17558294 doi: 10.1097/WNR.0b013e32818b2a0b

Morris, M. et al. Age-appropriate cognition and subtle dopamine-independent motor deficits in aged tau knockout mice. Neurobiol. Aging 34, 1523–1529 (2013).

pubmed: 23332171 pmcid: 3596503 doi: 10.1016/j.neurobiolaging.2012.12.003

Li, Z., Hall, A. M., Kelinske, M. & Roberson, E. D. Seizure resistance without parkinsonism in aged mice after tau reduction. Neurobiol. Aging 35, 2617–2624 (2014).

pubmed: 24908165 pmcid: 4171213 doi: 10.1016/j.neurobiolaging.2014.05.001

Tabrizi, S. J. et al. Targeting Huntingtin expression in patients with Huntington’s disease. N. Engl. J. Med. 380, 2307–2316 (2019).

pubmed: 31059641 doi: 10.1056/NEJMoa1900907

Miller, T. et al. Phase 1–2 trial of antisense oligonucleotide tofersen for SOD1 ALS. N. Engl. J. Med. 383, 109–119 (2020).

pubmed: 32640130 doi: 10.1056/NEJMoa2003715

Sato, C. et al. Tau kinetics in neurons and the human central nervous system. Neuron 98, 861–864 (2018).

pubmed: 29772204 pmcid: 6192252 doi: 10.1016/j.neuron.2018.04.035

Sandusky-Beltran, L. A. & Sigurdsson, E. M. Tau immunotherapies: lessons learned, current status and future considerations. Neuropharmacology 175, 108104 (2020).

pubmed: 32360477 pmcid: 7492435 doi: 10.1016/j.neuropharm.2020.108104

Luo, W. et al. Microglial internalization and degradation of pathological tau is enhanced by an anti-tau monoclonal antibody. Sci. Rep. 5, 11161 (2015).

pubmed: 26057852 pmcid: 4460904 doi: 10.1038/srep11161

Yamada, K. et al. Analysis of in vivo turnover of tau in a mouse model of tauopathy. Mol. Neurodegener. 10, 55 (2015).

pubmed: 26502977 pmcid: 4621881 doi: 10.1186/s13024-015-0052-5

Schoch, K. M. & Miller, T. M. Antisense oligonucleotides: translation from mouse models to human neurodegenerative diseases. Neuron 94, 1056–1070 (2017).

pubmed: 28641106 pmcid: 5821515 doi: 10.1016/j.neuron.2017.04.010

Novak, G. et al. Changes in brain volume with bapineuzumab in mild to moderate Alzheimer’s disease. J. Alzheimers Dis. 49, 1123–1134 (2016).

pubmed: 26639957 doi: 10.3233/JAD-150448

Fox, N. C. et al. Effects of Aβ immunization (AN1792) on MRI measures of cerebral volume in Alzheimer disease. Neurology 64, 1563–1572 (2005).

pubmed: 15883317 doi: 10.1212/01.WNL.0000159743.08996.99

Sur, C. et al. BACE inhibition causes rapid, regional, and non-progressive volume reduction in Alzheimer’s disease brain. Brain 143, 3816–3826 (2020).

pubmed: 33253354 pmcid: 8453290 doi: 10.1093/brain/awaa332

Salloway, S. et al. A phase 2 randomized trial of ELND005, scyllo-inositol, in mild to moderate Alzheimer disease. Neurology 77, 1253–1262 (2011).

pubmed: 21917766 pmcid: 3179648 doi: 10.1212/WNL.0b013e3182309fa5

Nave, S. et al. Sembragiline in moderate Alzheimer’s disease: results of a randomized, double-blind, placebo-controlled phase II trial (MAyflOwer RoAD). J. Alzheimers Dis. 58, 1217–1228 (2017).

pubmed: 28550255 pmcid: 5523913 doi: 10.3233/JAD-161309

Doody, R. S., Farlow, M., Aisen, P. S., & Alzheimer’s Disease Cooperative Study Data Analysis and Publication Committee Phase 3 trials of solanezumab and bapineuzumab for Alzheimer’s disease. N. Engl. J. Med. 370, 1460 (2014).

pubmed: 24716687 doi: 10.1056/NEJMoa1312889

Pasquier, F. et al. Two phase 2 multiple ascending-dose studies of vanutide cridificar (ACC-001) and QS-21 adjuvant in mild-to-moderate Alzheimer’s disease. J. Alzheimers Dis. 51, 1131–1143 (2016).

pubmed: 26967206 doi: 10.3233/JAD-150376

Siemers, E. R. et al. Phase 3 solanezumab trials: secondary outcomes in mild Alzheimer’s disease patients. Alzheimers Dement. 12, 110–120 (2016).

pubmed: 26238576 doi: 10.1016/j.jalz.2015.06.1893

Leung, K. K. et al. Cerebral atrophy in mild cognitive impairment and Alzheimer disease: rates and acceleration. Neurology 80, 648–654 (2013).

pubmed: 23303849 pmcid: 3590059 doi: 10.1212/WNL.0b013e318281ccd3

Nestor, S. M. et al. Ventricular enlargement as a possible measure of Alzheimer’s disease progression validated using the Alzheimer’s disease neuroimaging initiative database. Brain 131, 2443–2454 (2008).

pubmed: 18669512 pmcid: 2724905 doi: 10.1093/brain/awn146

Leng, F. & Edison, P. Neuroinflammation and microglial activation in Alzheimer disease: where do we go from here? Nat. Rev. Neurol. 17, 157–172 (2021).

pubmed: 33318676 doi: 10.1038/s41582-020-00435-y

Zivadinov, R. et al. Mechanisms of action of disease-modifying agents and brain volume changes in multiple sclerosis. Neurology 71, 136–144 (2008).

pubmed: 18606968 doi: 10.1212/01.wnl.0000316810.01120.05

De Stefano, N. & Arnold, D. L. Towards a better understanding of pseudoatrophy in the brain of multiple sclerosis patients. Mult. Scler. 21, 675–676 (2015).

pubmed: 25623248 doi: 10.1177/1352458514564494

Salloway, S. et al. Two phase 3 trials of bapineuzumab in mild-to-moderate Alzheimer’s disease. N. Engl. J. Med. 370, 322–333 (2014).

pubmed: 24450891 pmcid: 4159618 doi: 10.1056/NEJMoa1304839

Manning, E. N. et al. A comparison of accelerated and non-accelerated MRI scans for brain volume and boundary shift integral measures of volume change: evidence from the ADNI dataset. Neuroinformatics 15, 215–226 (2017).

pubmed: 28316055 pmcid: 5443885 doi: 10.1007/s12021-017-9326-0

Miller, T. M. et al. Trial of antisense oligonucleotide tofersen for SOD1 ALS. N. Engl. J. Med. 387, 1099–1110 (2022).

pubmed: 36129998 doi: 10.1056/NEJMoa2204705

Schobel, S. A. Preliminary results from GENERATION HD1, a phase III trial of tominersen in individuals with manifest HD. In CHDI 16th Annual HD Therapeutics Conference (2021).

Viglietta, V. A Ph1b/2a study of WVE-003, an investigational allele-selective, mHTT–lowering oligonucleotide for the treatment of early manifest Huntington’s disease, and review of PRECISION-HD results. In CHDI 16th Annual HD Therapeutics Conference (2021).

Biogen. SPINRAZA. Prescribing information https://www.spinrazahcp.com/content/dam/commercial/spinraza/hcp/en_us/pdf/spinraza-prescribing-information.pdf (2020).

Tabrizi, S. J. et al. Potential disease-modifying therapies for Huntington’s disease: lessons learned and future opportunities. Lancet Neurol. 21, 645–658 (2022).

pubmed: 35716694 pmcid: 7613206 doi: 10.1016/S1474-4422(22)00121-1

Morris, J. C. et al. Clinical dementia rating training and reliability in multicenter studies: the Alzheimer’s Disease Cooperative Study experience. Neurology 48, 1508–1510 (1997).

pubmed: 9191756 doi: 10.1212/WNL.48.6.1508

Folstein, M. F., Folstein, S. E. & McHugh, P. R. “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. J. Psychiatr. Res 12, 189–198 (1975).

pubmed: 1202204 doi: 10.1016/0022-3956(75)90026-6

Albert, M. S. et al. The diagnosis of mild cognitive impairment due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement. 7, 270–279 (2011).

pubmed: 21514249 pmcid: 3312027 doi: 10.1016/j.jalz.2011.03.008

Bennett, C. F. & Swayze, E. E. RNA targeting therapeutics: molecular mechanisms of antisense oligonucleotides as a therapeutic platform. Annu. Rev. Pharmacol. Toxicol. 50, 259–293 (2010).

pubmed: 20055705 doi: 10.1146/annurev.pharmtox.010909.105654

Wang, X. et al. [P4–266]: application of a multi-atlas segmentation tool to hippocampus, ventricle and whole brain segmentation. Alzheimers Dement. 13, P1385–P1386 (2017).