Idioma:

Effect of Immunotherapy With Bapineuzumab on Cerebrospinal Fluid Biomarker Levels in Patients With Mild to Moderate Alzheimer Disease

Blennow, Kaj ; Zetterberg, Henrik ; Rinne, Juha O ; Salloway, Stephen ; Wei, Jenny ; Black, Ronald ; Grundman, Michael ; Liu, Enchi

Archives of neurology (Chicago), 2012-08, Vol.69 (8), p.1002-1010

Chicago, IL: American Medical Association

Texto completo disponível

Citações Citado por

Enviar para

Título:
Effect of Immunotherapy With Bapineuzumab on Cerebrospinal Fluid Biomarker Levels in Patients With Mild to Moderate Alzheimer Disease
Autor: Blennow, Kaj ; Zetterberg, Henrik ; Rinne, Juha O ; Salloway, Stephen ; Wei, Jenny ; Black, Ronald ; Grundman, Michael ; Liu, Enchi
Assuntos: Aged ; Alzheimer Disease ; Alzheimer Disease - cerebrospinal fluid ; Alzheimer Disease - drug therapy ; Alzheimer Disease - epidemiology ; Alzheimer's disease ; Amyloid beta-Peptides ; Amyloid beta-Peptides - cerebrospinal fluid ; Antibodies ; Antibodies, Monoclonal, Humanized - therapeutic use ; Biological and medical sciences ; Biological Markers ; Biomarkers ; Biomarkers - cerebrospinal fluid ; Brain ; cerebrospinal fluid ; Clinical trials ; Cohort Studies ; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases ; Double-Blind Method ; drug therapy ; England ; England - epidemiology ; epidemiology ; Female ; Finland ; Finland - epidemiology ; Homeostasis ; Humanized ; Humans ; Immunotherapy ; Immunotherapy - methods ; Male ; Medical sciences ; methods ; Middle Aged ; Monoclonal ; Neurology ; Neurosciences ; Neurovetenskaper ; Patients ; Peptide Fragments ; Peptide Fragments - cerebrospinal fluid ; tau Proteins ; tau Proteins - cerebrospinal fluid ; therapeutic use ; Treatment Outcome ; United States ; United States - epidemiology
É parte de: Archives of neurology (Chicago), 2012-08, Vol.69 (8), p.1002-1010
Notas: ObjectType-Article-2
SourceType-Scholarly Journals-1
ObjectType-Feature-1
ObjectType-News-3
content type line 23
Descrição: BACKGROUND Given the slow and variable clinical course of Alzheimer disease, very large and extended clinical trials are needed to identify a beneficial clinical effect of disease-modifying treatments. Therefore, biomarkers are essential to prove that an anti–β-amyloid (Aβ) drug candidate affects both Aβ metabolism and plaque load as well as downstream pathogenic mechanisms. OBJECTIVE To evaluate the effect of the anti-Aβ monoclonal antibody bapineuzumab on cerebrospinal fluid (CSF) biomarkers reflecting Aβ homeostasis, neuronal degeneration, and tau-related pathology in patients with Alzheimer disease. DESIGN Two phase 2, multicenter, randomized, double-blind, placebo-controlled clinical trials of 12-month duration. SETTING Academic centers in the United States (Study 201) and England and Finland (Study 202). PATIENTS Forty-six patients with mild to moderate Alzheimer disease. INTERVENTIONS Patients received either placebo (n = 19) or bapineuzumab (n = 27) in 3 or 4 ascending dose groups. MAIN OUTCOME MEASURES Changes between end of study and baseline in the exploratory CSF biomarkers Aβ1-42, AβX-42, AβX-40; total tau (T-tau); and phosphorylated tau (P-tau). RESULTS Within the bapineuzumab group, a decrease at end of study compared with baseline was found both for CSF T-tau (−72.3 pg/mL) and P-tau (−9.9 pg/mL). When comparing the treatment and placebo groups, this difference was statistically significant for P-tau (P = .03), while a similar trend for a decrease was found for T-tau (P = .09). No clear-cut differences were observed for CSF Aβ. CONCLUSIONS To our knowledge, this study is the first to show that passive Aβ immunotherapy with bapineuzumab results in decreases in CSF T-tau and P-tau, which may indicate downstream effects on the degenerative process. Cerebrospinal fluid biomarkers may be useful to monitor the effects of novel disease-modifying anti-Aβ drugs in clinical trials. TRIAL REGISTRATIONS clinicaltrials.gov Identifier: NCT00112073, EudraCT Identifier: 2004-004120-12, and isrctn.org Identifier: ISRCTN17517446.
Editor: Chicago, IL: American Medical Association
Idioma: Inglês

Links

Voltar para lista de resultados

Realização: Logos de Redes Sociais:

Effect of Immunotherapy With Bapineuzumab on Cerebrospinal Fluid Biomarker Levels in Patients With Mild to Moderate Alzheimer Disease

Blennow, Kaj ; Zetterberg, Henrik ; Rinne, Juha O ; Salloway, Stephen ; Wei, Jenny ; Black, Ronald ; Grundman, Michael ; Liu, Enchi

Chicago, IL: American Medical Association

Buscando em bases de dados remotas. Favor aguardar.