Experiences from Clinical Research and Routine Use of Florbetaben Amyloid PET—A Decade of Post-Authorization Insights DOI Creative Commons
Aleksandar Jovalekic, Santiago Bullich, Núria Roé-Vellvé

et al.

Pharmaceuticals, Journal Year: 2024, Volume and Issue: 17(12), P. 1648 - 1648

Published: Dec. 7, 2024

Florbetaben (FBB) is a radiopharmaceutical approved by the FDA and EMA in 2014 for positron emission tomography (PET) imaging of brain amyloid deposition patients with cognitive impairment who are being evaluated Alzheimer’s disease (AD) or other causes decline. Initially, clinical adoption FBB PET faced significant barriers, including reimbursement challenges uncertainties regarding its integration into diagnostic practice. This review examines progress made overcoming these obstacles describes concurrent evolution landscape. Advances quantification methods have further strengthened traditional visual assessment approach. Over past decade, compelling evidence has emerged, demonstrating that strong impact on AD diagnosis, management, outcomes across diverse scenarios, even absence amyloid-targeted therapies. Amyloid become essential trials application new therapeutics, particularly confirming eligibility criteria (i.e., presence plaques) monitoring biological responses to amyloid-lowering Since approval, transitioned from purely tool aimed primarily at excluding pathology critical component drug development, today, it workup therapy management treatments.

Language: Английский

Amyloid-related imaging abnormalities: manifestations, metrics and mechanisms DOI
Steven M. Greenberg, Francesco Bax, Susanne J. van Veluw

et al.

Nature Reviews Neurology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 10, 2025

Language: Английский

Citations

9
What are the reasons for the repeated failures of clinical trials with anti-amyloid drugs for AD treatment? DOI Creative Commons
Orestes Vicente Forlenza, Breno José Alencar Pires Barbosa

Dementia & Neuropsychologia, Journal Year: 2025, Volume and Issue: 19

Published: Jan. 1, 2025

Language: Английский

Citations

0
Fc-engineered large molecules targeting blood-brain barrier transferrin receptor and CD98hc have distinct central nervous system and peripheral biodistribution DOI Creative Commons

Nathalie Khoury,

Michelle E. Pizzo,

Claire B. Discenza

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Feb. 20, 2025

Blood brain barrier-crossing molecules targeting transferrin receptor (TfR) and CD98 heavy chain (CD98hc) are widely reported to promote enhanced delivery of therapeutics. Here, we provide a comprehensive unbiased biodistribution characterization TfR CD98hc antibody transport vehicles (ATVTfR ATVCD98hc) compared control IgG. Mouse whole-body tissue clearing reveals distinct organ localization for each molecule. In the brain, ATVTfR ATVCD98hc achieve exposure parenchymal distribution even when exposures matched between ATV IgG in bulk tissue. Using combination cell sorting single-cell RNAseq, reveal that is nearly absent from cells distributed primarily perivascular leptomeningeal cells. contrast, exhibit broad unique cell-type distribution. Finally, profile detail region-specific cynomolgus monkey spinal cord. Taken together, this in-depth multiscale will guide platform selection therapeutic targets interest.

Language: Английский

Citations

0
Anti-Aβ immunotherapy-mediated amyloid clearance attenuates microglial activation without inducing exhaustion at residual plaques DOI Creative Commons
Lis de Weerd, Selina Hummel, Stephan A. Müller

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: April 17, 2025

Abstract Anti-amyloid β-peptide (Aβ) immunotherapy was developed to reduce amyloid plaque pathology and slow cognitive decline during progression of Alzheimer’s disease. Efficient clearance has been proven in clinical trials testing anti-Aβ antibodies, with the impact on endpoints correlating extent removal. However, treatment is associated adverse side-effects, such as oedema haemorrhages, which are potentially linked induced immune response. To improve safety profile these molecules, it imperative understand consequences antibody cell function. Here, we investigated effects long-term chronic microglial response APP-SAA triple knock-in mouse model. Mice were treated weekly from 4-8 months age. Long-term results a robust dose-dependent removal pathology, higher efficiency for removing diffuse over dense-core plaques. Analysis CSF proteome indicates reduction markers neurodegeneration including Tau α-Synuclein, well related proteins. Bulk RNA-seq revealed decrease brain-wide disease-associated (DAM) glycolytic gene expression, supported by parallel glucose uptake protein levels Triggering receptor myeloid cells 2 (Trem2) protein, major involved DAM activation microglia. In contrast, around remaining plaques remains high regardless dose. addition, microglia surrounding display increase clustering selective antigen presenting signalling These findings demonstrate that mediated Aβ leads dose dependent neurodegeneration, while at residual combined phenotype suggests continued Figure Graphical abstract: Schematic overview mice created BioRender.com

Language: Английский

Citations

0
Experiences from Clinical Research and Routine Use of Florbetaben Amyloid PET—A Decade of Post-Authorization Insights DOI Creative Commons
Aleksandar Jovalekic, Santiago Bullich, Núria Roé-Vellvé

et al.

Pharmaceuticals, Journal Year: 2024, Volume and Issue: 17(12), P. 1648 - 1648

Published: Dec. 7, 2024

Florbetaben (FBB) is a radiopharmaceutical approved by the FDA and EMA in 2014 for positron emission tomography (PET) imaging of brain amyloid deposition patients with cognitive impairment who are being evaluated Alzheimer’s disease (AD) or other causes decline. Initially, clinical adoption FBB PET faced significant barriers, including reimbursement challenges uncertainties regarding its integration into diagnostic practice. This review examines progress made overcoming these obstacles describes concurrent evolution landscape. Advances quantification methods have further strengthened traditional visual assessment approach. Over past decade, compelling evidence has emerged, demonstrating that strong impact on AD diagnosis, management, outcomes across diverse scenarios, even absence amyloid-targeted therapies. Amyloid become essential trials application new therapeutics, particularly confirming eligibility criteria (i.e., presence plaques) monitoring biological responses to amyloid-lowering Since approval, transitioned from purely tool aimed primarily at excluding pathology critical component drug development, today, it workup therapy management treatments.

Language: Английский

Citations

0