- |||||||||| bapineuzumab (AAB-001) / Pfizer, J&J, Perrigo Company
Deciphering the role of complement C3 in anti-amyloid antibody-induced ARIA (MCP Hall A) - Aug 22, 2024 - Abstract #Neuroscience2024Neuroscience_1110;
mAb, a murine analog of bapineuzumab known to cause microhemorrhages, for 7 weeks...Our results suggest that C3 lowering might protect against anti-amyloid-induced microhemorrhages. Additional analyses are underway to identify mechanisms underlying this process and the potential of C3 as a therapeutical target for AD.
- |||||||||| Review, Journal: Engineered Antibodies to Improve Efficacy against Neurodegenerative Disorders. (Pubmed Central) - Jun 27, 2024
The identified products can be readily tested and returned to patients with the lowest regulatory cost and delays. These engineered antibodies can be manufactured by recombinant engineering, preferably by mRNA technology, as a more affordable solution to meet the dire need to treat neurodegenerative disorders effectively.
- |||||||||| bapineuzumab (AAB-001) / Pfizer, J&J, Perrigo Company
(In)Equity in Alzheimer's Clinical Trials: A Long Road Ahead? (Exhibit (Pennsylvania Convention Center); In-Person) - Jun 19, 2024 - Abstract #AAIC2024AAIC_3251;
It ultimately increases the disparities presented in the diagnosis and treatment of individuals with dementia. Ideally, anti-amyloid trials should incorporate the epidemiology of individuals with dementia worldwide.
- |||||||||| Review, Journal: Risk factors in developing amyloid related imaging abnormalities (ARIA) and clinical implications. (Pubmed Central) - Feb 5, 2024
This review aims to discuss risk factors of ARIA and highlight important areas for further research. With more anti-amyloid monoclonal antibodies approved by the Food and Drug Administration, considering patient risk factors for developing ARIA is important to identify to minimize patient's risk while receiving these new therapies.
- |||||||||| semagacestat (LY450139) / Eli Lilly, bapineuzumab (AAB-001) / Pfizer, J&J, Perrigo Company
Clinical: Characterizing Treatment Non-responders vs. Responders in Completed Alzheimer's Disease Clinical Trials. (Pubmed Central) - Nov 14, 2023
4 "negative" treatment trials had subsets of patients who had, in fact, responded. This study suggests that analyzing heterogeneity in treatment effects in "positive" or "negative" trials may be a very powerful tool for identifying distinct subgroups that are responsive to treatments, which may significantly benefit future clinical trial design and interpretation.
- |||||||||| Journal: A combined PBPK and QSP model for modeling amyloid aggregation in Alzheimer's Disease. (Pubmed Central) - Jan 13, 2023
ARIA-E is well predicted for all antibodies except bapineuzumab. This QSP model could support clinical trial design of different amyloid modulating interventions, define optimal titration and maintenance schedules and provide a first step to understand the variability of biomarker response in clinical practice.
- |||||||||| bapineuzumab (AAB-001) / Pfizer, J&J, Perrigo Company
Preclinical, Journal: ImmunoPET imaging of amyloid-beta in a rat model of Alzheimer's disease with a bispecific, brain-penetrating fusion protein. (Pubmed Central) - Dec 26, 2022
Affinity to TfR affects how efficiently a TfR-targeting bispecific fusion protein will cross the BBB, such that the higher-affinity bispecific fusion protein crossed the BBB more efficiently. Furthermore, bispecific immunoPET imaging of brain Aβ pathology using TfR-mediated transport provides good imaging contrast between TgF344-AD and WT rats, suggesting that this immunoPET strategy has the potential to be translated to higher species.
- |||||||||| bapineuzumab (AAB-001) / Pfizer, J&J, Perrigo Company
BISPECIFIC ABETA ANTIBODIES WITH OPTIMIZED BIOLOGICAL HALF-LIFE FOR IMMUNO-PET (EXHIBITION) - Dec 23, 2022 - Abstract #ADPD2023ADPD_1501;
Bispecific antibodies, based on Bapineuzumab (Bapi), either with or without a mutation in the FcRn binding domain, were recombinantly expressed in CHO cells... The impairment of the FcRn is a promising method to shorten the biological half -life of antibodies to get one step closer towards the usage of biologicals as PET agents.
- |||||||||| Aduhelm (aducanumab) / Eisai, Biogen, gantenerumab (RG1450) / Roche, MorphoSys, bapineuzumab (AAB-001) / Pfizer, J&J, Perrigo Company
Journal: Therapeutic anti-amyloid β antibodies cause neuronal disturbances. (Pubmed Central) - Dec 16, 2022
Anti-Aβ antibody treatment of neurons or neurons co-cultured with microglia led to activation of a substantial number of allergenic-related genes. These allergenic-related genes are associated with endothelial dysfunction possibly responsible for ARIA.
- |||||||||| ACU193 / Acumen Pharma
Clinical, Review, Journal: ACU193: An Immunotherapeutic Poised to Test the Amyloid β Oligomer Hypothesis of Alzheimer's Disease. (Pubmed Central) - May 14, 2022
More than 25 negative randomized clinical trials (RCTs) have evaluated Aβ-targeting therapeutics, yet none has directly evaluated whether selective blockage of disease-relevant AβOs can stop or reverse AD-associated cognitive decline. Here, we briefly summarize studies that establish the AD therapeutic rationale to target AβOs selectively, and we describe ACU193, the first AβO-selective immunotherapeutic to enter human clinical trials and the first positioned to test the AβO hypothesis of AD.
- |||||||||| gantenerumab (RG1450) / Roche, MorphoSys
New P3 trial, P3 data, Journal: Disease Modeling and Model-Based Meta-Analyses to Define a New Direction for a Phase III Program of Gantenerumab in Alzheimer's Disease. (Pubmed Central) - Apr 23, 2022
P3
Multiple regimens were designed to gradually up-titrate participants to the target dose of 1200 mg gantenerumab every four weeks to mitigate the increased risk of ARIA-E events that may be associated with higher doses of anti-amyloid-beta antibodies. Favorable OLE data that matched well with model predictions supported the decision to continue the gantenerumab clinical development program and further apply model-based analytical techniques to optimize the design of new Phase III studies.
- |||||||||| bapineuzumab (AAB-001) / Pfizer, J&J, Perrigo Company
IMMUNOPET IMAGING OF AMYLOID-BETA IN THE TGF344-AD RAT MODEL (HALL B) - Mar 9, 2022 - Abstract #ADPD2022ADPD_1023;
F(ab’)2 fragments of the AΒ antibody, Bapineuzumab (Bapi), were chemically conjugated to one of two affinity variants for the rat TfR antibody, OX26 (OX265 or OX2676), to create two bispecific fusion proteins: OX265-F(ab’)2-Bapi and OX2676-F(ab’)2-Bapi... Antibody-based PET imaging of brain AΒ pathology using TfR-mediated transport was successful in an AD rat model suggesting that this strategy could be translated from bench to bedside with the correct human anti-TfR antibody.
- |||||||||| bapineuzumab (AAB-001) / Pfizer, J&J, Perrigo Company, crenezumab (MABT5102A) / Roche
Journal, Heterogeneity: N-terminal heterogeneity of parenchymal and vascular amyloid-β deposits in Alzheimer's disease. (Pubmed Central) - Oct 30, 2021
This suggests conformational preferences of this antibody. The diverse composition of plaques and vascular deposits stresses the importance of understanding the roles of various Aβ variants during disease development and progression in order to generate appropriate target-developed therapies.
- |||||||||| https://t.co/2kmoEtPV2I and after semagacestat, bapineuzumab, solanezumab, gantenerumab, crenezumab, verubecestat, lanabecestat, atabecestat, umibecestat, & elenbecestat had ALL failed to prove the amyloid-beta hypothesis. Stunning. (Twitter) - Jun 9, 2021
- |||||||||| bapineuzumab (AAB-001) / Pfizer, J&J, Perrigo Company
Observational data, Preclinical, Journal: Progression of Alzheimer's disease and effect of scFv-h3D6 immunotherapy in the 3xTg-AD mouse model: An in vivo longitudinal study using Magnetic Resonance Imaging and Spectroscopy. (Pubmed Central) - Jun 3, 2021
One strategy consists of using single-chain variable fragments (scFvs), which avoids the fragment crystallizable (Fc) effects that are supposed to trigger a microglial response, leading to microhemorrhages and vasogenic edemas, as evidenced in clinical trials with bapineuzumab...Compared with the genetic background, 3xTg-AD mice presented a smaller volume in almost all cerebral regions and ages examined, an increase in both the intra and extracellular Aβ at 12-mo, and an inflammation process at this age, in both the hippocampus (IL-6 and mIns) and cortex (IL-6). In addition, treatment with scFv-h3D6 partially recovered the values in brain volume, and Aβ, IL-6, and mIns concentrations, among others, encouraging further studies with this antibody fragment.
- |||||||||| bapineuzumab (AAB-001) / Pfizer, J&J, Perrigo Company
Journal: Brain delivery of biologics using a cross-species reactive transferrin receptor 1 VNAR shuttle. (Pubmed Central) - May 1, 2021
TXB2 was fused to a human IgG1 Fc domain (hFc) or to the amyloid-β (Aβ) antibody bapineuzumab (Bapi)...PET imaging and ex vivo autoradiography revealed more parenchymal distribution of Bapi-TXB2 compared with Bapi. In conclusion, the TXB2 VNAR shuttle markedly increased brain uptake of protein cargo and increased brain concentrations of the Aβ binding antibody Bapi.
- |||||||||| ibuprofen / Generic mfg.
Review, Journal: Exploring the Potential of Therapeutic Agents Targeted towards Mitigating the Events Associated with Amyloid-β Cascade in Alzheimer's Disease. (Pubmed Central) - Feb 27, 2021
The authors discuss treatment possibilities, including the inhibition of β- and γ-secretase-mediated enzymatic cleavage of APP, the immune response generating active immunotherapy and passive immunotherapeutic approaches targeting monoclonal antibodies towards Aβ aggregates, the removal of amyloid aggregates by the activation of enzymatic pathways or the regulation of Aβ circulation, glucagon-like peptide-1 (GLP-1)-mediated curbed accumulation and the neurotoxic potential of Aβ aggregates, bapineuzumab-mediated vascular permeability alterations, statin-mediated Aβ peptide degradation, the potential role of ibuprofen and the significance of natural drugs and dyes in hindering the amyloid cascade events. Thus, the authors aim to highlight the treatment perspective, targeting the amyloid hypothesis, while simultaneously emphasizing the need to conduct further investigations, in order to provide an opportunity to neurologists to develop novel and reliable treatment therapies for the retardation of AD progression.
- |||||||||| Journal: Kinetic fingerprints differentiate the mechanisms of action of anti-Aβ antibodies. (Pubmed Central) - Feb 10, 2021
We quantify the influence of these antibodies on the aggregation kinetics and on the production of oligomeric aggregates and link these effects to the affinity and stoichiometry of each antibody for monomeric and fibrillar forms of Aβ. Our results reveal that, uniquely among these four antibodies, aducanumab dramatically reduces the flux of Aβ oligomers.
- |||||||||| Journal, IO biomarker: Passive antiamyloid immunotherapy for Alzheimer's disease. (Pubmed Central) - Feb 2, 2021
The high incidence of ARIAs indicates that the risk of adverse events may outweigh the benefits of these interventions. Ongoing studies must determine the benefit of such interventions in preclinical Alzheimer's disease, addressing the effect of antiamyloid immunotherapy in samples of asymptomatic carriers of autosomal-dominant mutations related to early-onset Alzheimer's disease.
- |||||||||| bapineuzumab (AAB-001) / Pfizer, J&J, Perrigo Company
Preclinical, Journal: Treatment with scFv-h3D6 Prevented Neuronal Loss and Improved Spatial Memory in Young 3xTg-AD Mice by Reducing the Intracellular Amyloid-β Burden. (Pubmed Central) - Oct 11, 2020
In the present study, we assessed the effect of scFv-h3D6, an anti-Aβ single-chain variable fragment (scFv) derived from the antibody bapineuzumab, on amyloid pathology in 5-month-old 3xTg-AD female mice, focusing on intracellular Aβ clearance, neuronal survival, and functional abilities...These findings indicated that the mechanism underlying the therapeutic effect of scFv-h3D6 was the clearance of intracellular Aβ, with subsequent prevention of neuronal loss and amelioration of cognitive disabilities. The treatment was safe in terms of neuroinflammation and kidney and liver function, whereas some effects on the spleen were observed.
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