2019, Número 627
<< Anterior Siguiente >>
Rev Med Cos Cen 2019; 85 (627)
Enfermedad de Alzheimer e Inmunoterapia: revisión de tres anticuerpos monoclonales humanizados dirigidos contra el Aβ amiloide (bapineuzumab, solaneuzumab y aducanumab)
Torrealba AG, Rojas DK, Salazar NJ
Idioma: Español
Referencias bibliográficas: 47
Paginas: 2-7
Archivo PDF: 105.57 Kb.
RESUMEN
La enfermedad de Alzheimer (EA) es un trastorno neurodegenerativo que constituye la causa más
frecuente de demencia en el adulto mayor. En el 2015 se le atribuyeron 46.8 millones casos de
demencia a nivel mundial y se proyecta que para el año 2050 ese número se haya triplicado. La EA
es una enfermedad crónica y progresiva donde las alteraciones funcionales y cognitivas van
acompañadas de un deterioro del control emocional y del comportamiento. A pesar de los grandes
avances científicos, los tratamientos disponibles actualmente para la EA son solo sintomáticos, es
decir, pueden lograr una mejoría en la calidad de vida de los pacientes, pero ninguno consigue
revertir, frenar o curar la fatal progresión de la enfermedad. La hipótesis amiloide propone que el
péptido Αβ amiloide tiene un papel clave en esta enfermedad ya que es neurotóxico, altera la
función sináptica y produce neurodegeneración. Dentro de las estrategias farmacológicas
enfocadas a inhibir la agregación del péptido Αβ amiloide. En esta revisión se presenta el resumen
de los resultados obtenidos en ensayos clínicos donde se ha evaluado la eficacia y seguridad de
anticuerpos monoclonales dirigidos contra el Αβ amiloide (bapineuzumab, solanezumab,
aducanumab).
REFERENCIAS (EN ESTE ARTÍCULO)
Scheltens P, Blennow K, Breteler,M, Strooper B. Alzheimer’s disease. Lancet. 2016; 388: 505–17.
Barnes J, Dickerson B, Frost C, Jiskoot LC, Wolk D, Van der Flier WM. Alzheimer’s disease first symptoms are age dependent: evidence from the NACC data set. Alzheimer’s Dement. 2015; 11: 1349–57.
Murray ME, Graff-Radford NR, Ross OA, Petersen RC, Duara R, Dickson DW. Neuropathologically defined subtypes of Alzheimer’s disease with distinct clinical characteristics: a retrospective study. Lancet Neurol. 2011; 10: 785–96.
Aguzzi A. Neurodegeneration: Alzheimer’s disease under strain. Nature .2014; 512:32-4.
Alzheimer’s Disease International, 2015. https://www.alz.co.uk/research/ WorldAlzheimerReport2015.pdf. Accessed 25 May 2016.
Vradenburg G. A pivotal moment in Alzheimer’s disease and dementia: how global unity of purpose and action can beat the disease by 2025. Expert Rev Neurother. 2015; 15:73–82.
National Alzheimer’s Project Act. http://napa.alz.org/nationalalzheimers- project-act-backgroun. Accessed 25 May 2016.
Huang Y, Mucke L. Alzheimer mechanisms and therapeutic strategies. Cell. 2012; 148:1204-22.
Chiang K, Koo EH. Emerging therapeutics for Alzheimer’s disease. Annu Rev Pharmacol Toxicol. 2014; 54:381-405.
Prince M, Bryce R, Albanese E, Wimo A, Ribeiro W, Ferri CP. The global prevalence of dementia: a systematic review and metaanalysis. Alzheimers Dement. 2013; 9:63-75.
Winblad B, Amouyel P, Andrieu S, et al. Defeating Alzheimer’s disease and other dementias: a priority for European science and society. Lancet Neurol. 2016; 15:455-532.
Lanctot KL, Herrmann N, Yau KK, Khan LR, Liu BA, LouLou MM, et al. Efficacy and safety of cholinesterase inhibitors in Alzheimer’s disease: a meta-analysis. CMAJ. 2003; 169:557-64.
Raina P, Santaguida P, Ismaila A, Patterson C, Cowan D, Levine M, et al. Effectiveness of cholinesterase inhibitors and memantine for treating dementia: evidence review for a clinical practice guideline. Ann Intern Med. 2008; 148:379-97.
Mangialasche F, Solomon A, Winblad B, Mecocci P, Kivipelto M. Alzheimer’s disease: clinical trials and drug development. Lancet Neurol. 2010; 9:702-16.
Bruno Dubois, Howard H Feldman, Claudia Jacova, Harald Hampel, Advancing research diagnostic criteria for Alzheimer’s disease: the IWG-2 criteria. Lancet Neurol 2014; 13: 614-29.
Cynis H, Frost J, Crehan H, Lemere C. Immunotherapy targeting pyroglutamate-3 Aβ: prospects and challenges. Molecular Neurodegeneration. 2016. DOI 10.1186/s13024-016-0115-2.
Hardy, J. A. & Higgins, G. A. Alzheimer’s disease: the amyloid cascade hypothesis. Science .1992; 256: 184-185.
Ising, C., Stanley, M. & Holtzman, D. M. Current thinking on the mechanistic basis of Alzheimer’s and implications for drug development. Clin. Pharmacol. Ther. 2015. 98; 469-471.
Selkoe, D. J. The therapeutics of Alzheimer’s disease: where we stand and where we are heading. Ann. Neurol. 2013. 74; 328-336.
Cummings, J. L., Morstorf, T. & Zhong, K. Alzheimer’s disease drugdevelopment pipeline: few candidates, frequent failures. Alzheimers ResTher. 2014; 74, 328-336.
Morkuniene, R. et al. Small Aβ1-42 oligomer-induced membrane depolarization of neuronal and microglial cells: role of N-methyl-daspartate receptors. J. Neurosci. Res. 2015. 93; 475-486.
Dean DN, Pate KM, Moss MA, Rangachari V. Conformational Dynamics of Specific Aβ Oligomers Govern Their Ability To Replicate and Induce Neuronal Apoptosis. Biochemistry. 2016. 19; 238-50.
Kumar A, Paslay LC, Lyons D, Morgan SE, Correia JJ, Rangachari V. Specific soluble oligomers of amyloid-β peptide undergo replication and form non-fibrillar aggregates in interfacial environments. J Biol Chem. 2012. 15; 287:21253-64.
Benseny-Cases N, Klementieva O, Cladera J. In vitro oligomerization and fibrillogenesis of amyloid-beta peptides. Subcell Biochem. 2012; 65:53-74.
Ferrera D, Mazzaro N, Canale C, Gasparini L. Resting microglia react to Aβ42 fibrils but do not detect oligomers or oligomer-induced neuronal damage. Neurobiol Aging. 2014; 35 :2444-57.
Gold M, El Khoury J. β-amyloid, microglia, and the inflammasome in Alzheimer's disease. Semin Immunopathol. 2015; 37:607-11.
Goldmann T, Tay TL, Prinz M. Love and death: microglia, NLRP3 and the Alzheimer's brain.Cell Res. 2013; 23:595-6.
Hickman SE, El Khoury J. The neuroimmune system in Alzheimer's disease: the glass is half full.J Alzheimers Dis. 2013; 33:S295-302.
Heneka M, Carson M, EL Goury J, Landreth G. Neuroinflammation in Alzheimer's disease.The Lancet Neurology. 2015; 14; 341-454.
Ousset P, Delrieu J. Nouvelles thérapeutiques dans la maladie d’Alzheimer.Neurologies.2011; 14 :494-502.
Anand R, Gill K, Mahdi A. Therapeutics of Alzheimer’s disease: Past, present and future. Neuropharmacology. 2014; 27:27-50.
Molin P, Rockwood K. Les nouveaux critères de la Maladie d’Alzheimer– Perspective gériatrique. CANADIAN GERIATRICS JOURNAL. 2016; 19:74-82.
Banzi R,Camaioni P,Tettamanti M, Bertele V. Older patients are still under-represented inclinical trials of Alzheimer’s disease. Alzheimer's Research & Therapy. 2016; 8:1-10.
Petrasek T, Skurlova M, Maleninska K, Vojtechova I y col. A Rat Model of Alzheimer’s Disease Based on Abeta 42 and Pro-oxidative Substances Exhibits Cognitive Deficitand Alterations in Glutamatergic and Cholinergic Neurotransmitter Systems. Front Aging Neurosci. 8:83. doi: 10.3389/fnagi.2016.00083.
Mazure C, Swendsen J. Sex differences in Alzheimer’s disease and other dementias. Lancet Neurol. 2016; April; 15: 451-452. doi: 10.1016/S1474-4422(16)00067-3.
Prieto C, Saiz D, Ubeda I, Flores A. Neurogenesis, Neurodegeneration, Interneuron Vulnerability and Amyloid bin The Olfactory Bulb Of APP/PS1MouseModelofAlzheimer’sDisease.Front.Neurosci.10:227.d oi:10.3389/fnins.2016.00227.
Spinney L. The forgetting gene. Nature.2014; 10:1-3.
Caoimh O, Svendrovski A, Johnston B ,Gao Y y col. The Quick Mild Cognitive Impairment screen correlated with the Standardized Alzheimer’s Disease Assessment Scaleecognitive section in clinical trials. Journal of Clinical Epidemiology 67 (2014); 87-92.
Scheltens P, Blennow K, Breteler M, Strooper B.y col. Alzheimer’s disease. www.thelancet.com Vol 388 July 30, 2016; 505-517.
Dansokho C, Ait Ahmed D, Aid S, Toly-Ndour C. Regulatory T cells delay disease progression in Alzheimer-like pathology. BRAIN 2016; 139; 1237-1251.
Lemere C. Immunotherapy for Alzheimer’s disease: hoops and hurdles. Molecular Neurodegeneration 2013; 8:36; 1-6.
Yang K ,Chen H. Probabilistic Cost-Effectiveness Analysis of Vaccination for Mild or Moderate Alzheimer’s Disease. Current Alzheimer Research, 2016; 13, 809-816.
Cornelis K. Muldera C, Donga Y, Bruggheb H, Timmermansb H y col. Immunization with SmallAmyloid-derived Cyclopeptide Conjugates Diminishes Amyloid-Induced Neurodegeneration in Mice. Journal of Alzheimer’s Disease 52 (2016); 1111-1123.
Khan A, Dobson R,Sattlecker M,3, Kiddle S. Alzheimer’s disease: are blood and brain markers related? A systematic review. Annals of Clinical and Translational Neurology 2016; 3(6): 455-462.
Doody R, Thomas R, Farlow M,Iwatsubo T y col. Phase 3 Trials of Solanezumab for Mild-to-Moderate Alzheimer’s Disease. N Engl J Med 2014; 370: 311-21.
Salloway S, Sperling R, Fox N, Blennow K y col, Two Phase 3 Trials of Bapineuzumab in Mild-to-Moderate Alzheimer’s Disease. N Engl J Med 2014; 370: 322-33.
Sevigny J, Chiao P, Bussière T, Weinreb P y col. The antibody aducanumab reduces Aβ plaques in Alzheimer’s disease. doi: 10.1038/nature19323.