AI Article Synopsis
- Cerebral amyloid angiopathy (CAA) leads to brain damage due to amyloid deposits, and this study tested the safety and efficacy of a new drug, ponezumab, in 36 patients aged 55-80 with probable CAA.
- Participants were given either ponezumab or a placebo, and cerebrovascular reactivity was measured before treatment and at 90 days after, revealing a non-significant trend favoring the placebo group at Day 90.
- Although ponezumab was found to be safe, the expected benefits in treatment efficacy weren't demonstrated, as the results did not support the primary goals of the study.
Article Abstract
Objective: Cerebral amyloid angiopathy (CAA) is caused by cerebrovascular deposition of -amyloid fragments leading to cerebrovascular dysfunction and other brain injuries. This phase 2, randomized, double-blind trial in patients with probable CAA assessed the efficacy and safety of ponezumab, a novel monoclonal antibody against A .
Methods: Thirty-six participants aged 55-80 years with probable CAA received intravenous placebo ( = 12) or ponezumab ( = 24). The change from baseline to Days 2 and 90 in cerebrovascular reactivity (CVR) was measured in the visual cortex as the natural log of the rising slope of the BOLD fMRI response to a visual stimulus. Safety and tolerability were also assessed.
Results: The mean change from baseline to Day 90 was 0.817 (ponezumab) and 0.958 (placebo): a mean ratio of 0.852 (90% CI 0.735-0.989) representing a trend towards CVR in the ponezumab group. This trend was not present at Day 2. There was one asymptomatic occurrence of amyloid-related imaging abnormality-edema in the ponezumab group. The total number of new cerebral microbleeds from baseline to day 90 did not differ between groups. The ponezumab group had a participant with nonfatal new cerebral hemorrhage with aphasia and a participant with subdural hemorrhage that site investigators deemed to be nondrug related. In the placebo group one participant had a fatal intracerebral hemorrhage and one participant had migraine with aura.
Interpretation: Ponezumab was safe and well-tolerated. The ponezumab group showed a trend towards treatment effect at Day 90 that was opposite to the hypothesized direction. The prespecified efficacy criteria were thus not met.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6469253 | PMC |
| http://dx.doi.org/10.1002/acn3.761 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Recent Updates in the Alzheimer's Disease Etiopathology and Possible Treatment Approaches: A Narrative Review of Current Clinical Trials.
Curr Mol Pharmacol
August 2021
Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran
Background: Alzheimer's disease (AD) is the most frequent subtype of incurable neurodegenerative dementias and its etiopathology is still not clearly elucidated.
Objective: Outline the ongoing clinical trials (CTs) in the field of AD, in order to find novel master regulators.
Methods: We strictly reviewed all scientific reports from Clinicaltrials.
Article Synopsis
- Cerebral amyloid angiopathy (CAA) leads to brain damage due to amyloid deposits, and this study tested the safety and efficacy of a new drug, ponezumab, in 36 patients aged 55-80 with probable CAA.
- Participants were given either ponezumab or a placebo, and cerebrovascular reactivity was measured before treatment and at 90 days after, revealing a non-significant trend favoring the placebo group at Day 90.
- Although ponezumab was found to be safe, the expected benefits in treatment efficacy weren't demonstrated, as the results did not support the primary goals of the study.
Safety and pharmacology of a single intravenous dose of ponezumab in subjects with mild-to-moderate Alzheimer disease: a phase I, randomized, placebo-controlled, double-blind, dose-escalation study.
Clin Neuropharmacol
October 2013
Global Research and Development, Pfizer Inc, Groton, CT 06340, USA.
Objectives: Ponezumab is a humanized antiamyloid beta (Aβ) monoclonal antibody designed to treat Alzheimer disease (AD).
Methods: This randomized, double-blind, single-dose-escalation study evaluated the safety, pharmacokinetics, and pharmacodynamics of 0.1, 0.
Chronic administration of an aglycosylated murine antibody of ponezumab does not worsen microhemorrhages in aged Tg2576 mice.
Curr Alzheimer Res
November 2012
Pfizer Worldwide Research and Development, Groton, CT 06340, USA.
Cerebral vasogenic edema and microhemorrhages are potential safety concerns for compounds intended to treat subjects with Alzheimer's disease (AD) by targeting amyloid β (Aβ). Ponezumab (PF-04360365) is an investigational anti-Aβ monoclonal antibody. Two hundred female mice (APP(K670N;M671L); Tg2576) 16-19 months old received an aglycosylated CHO-derived murine surrogate of ponezumab by intraperitoneal administration once weekly for up to 26 weeks at doses of 0, 10, 30, or 100 mg/kg.
View Article and Find Full Text PDFStructural basis of C-terminal β-amyloid peptide binding by the antibody ponezumab for the treatment of Alzheimer's disease.
J Mol Biol
August 2012
Rinat, Pfizer Inc., South San Francisco, CA 94080, USA.
Alzheimer's disease, the most common cause of dementia in the elderly and characterized by the deposition and accumulation of plaques, is composed in part of β-amyloid (Aβ) peptides, loss of neurons, and the accumulation of neurofibrillary tangles. Here, we describe ponezumab, a humanized monoclonal antibody, and show how it binds specifically to the carboxyl (C)-terminus of Aβ40. Ponezumab can label Aβ that is deposited in brain parenchyma found in sections from Alzheimer's disease casualties and in transgenic mouse models that overexpress Aβ.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!