Lipoic acid scaffold applications in the design of multitarget-directed ligands against Alzheimer’s disease

Bioorganic Chemistry, Год журнала: 2025, Номер 157, С. 108241 - 108241

Опубликована: Фев. 3, 2025

Язык: Английский

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A real-world disproportionality analysis of FDA adverse event reporting system (FAERS) events for lecanemab

Frontiers in Pharmacology, Год журнала: 2025, Номер 16

Опубликована: Апрель 2, 2025

Lecanemab is a humanized murine IgG1 antibody. Recent Phase 3 clinical trials have demonstrated its ability to reduce brain amyloid-β (Aβ) load and slow cognitive decline in patients with early Alzheimer's disease (AD). However, since approval, reports on adverse effects (AEs) associated lecanemab been limited. To better understand the AEs related provide guidance for future use, we analyzed lecanemab-associated using data from United States Food Drug Administration (FDA) Adverse Event Reporting System (FAERS). We extracted all FAERS database period first quarter of 2023 third 2024. Using Odds Ratio (ROR), Proportional (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), Multi-item Gamma Poisson Shrinker (MGPS) algorithms, conducted comprehensive analysis lecanemab-related AEs, restricting role code primary suspect (PS). A total 811 used AD 506 Non-AD were included. The preferred terms (PTs) identified as positive across four algorithms included headache, Amyloid Related Imaging Abnormalities-oedema/effusion (ARIA-E), chills, Abnormalities-haemosiderosis/microhaemorrhage (ARIA-H), fatigue, infusion-related reaction, nausea, pyrexia, pain, influenza like illness, so on. Among these, ARIA-E, ARIA-H, oedema status epilepticus Important Medical Events (IMEs) patients, oedema, cerebral haemorrhage, microhaemorrhage, subdural haematoma, ischaemic stroke, infarction IMEs patients. At system organ class (SOC) level, highest signal detection was observed nervous disorders among [ROR AD: 2.42 (2.2-2.65); ROR Non-AD: 6.97 (6.12-7.95)]. median time occurrence these 44 days after administration 30 This study utilized evaluate non-AD along their temporal patterns post-marketing authorization, thereby establishing foundation subsequent pharmacovigilance. biweekly 10 mg/kg optimal therapeutic dosage. ARIA emerged frequent treatment-related APOEɛ4 carriers demonstrating heightened susceptibility. necessitates serial MRI surveillance during treatment, aimed not only at but also vigilant monitoring including microhaemorrhages, edema, infarction. While predominantly exhibited non-specific manifestations, cohorts showed elevated risks stroke-related complications. Consequently, dynamic neurological deficit indispensable populations receiving mitigate outcomes. Finally, reassessment anticoagulant or antiplatelet therapy indications warranted both hemorrhagic risks.

Язык: Английский

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CRISPR/Cas9-Based therapeutics as a promising strategy for management of Alzheimer’s disease: progress and prospects

Frontiers in Cellular Neuroscience, Год журнала: 2025, Номер 19

Опубликована: Апрель 7, 2025

CRISPR/Cas9 technology has revolutionized genetic and biomedical research in recent years. It enables editing modulation of gene function with an unparalleled precision effectiveness. Among the various applications prospects this technology, opportunities it offers unraveling molecular underpinnings a myriad central nervous system diseases, including neurodegenerative disorders, psychiatric conditions, developmental abnormalities, are unprecedented. In review, we highlight CRISPR/Cas9-based therapeutics as promising strategy for management Alzheimer's disease transformative impact on AD research. Further, emphasize role generating accurate models identification novel therapeutic targets, besides CRISPR-based therapies aimed at correcting AD-associated mutations modulating processes. Furthermore, delivery systems reviewed potential non-viral nanotechnology-based carriers overcoming critical limitations effective is discussed. Overall, review highlights promise intricate processes underlying development AD, discusses its limitations, ethical concerns several challenges efficient across BBB, ensuring specificity, avoiding off-target effects. This article can be helpful better understanding based approaches way forward utilizing enormous targeted, gene-specific treatments that could change trajectory debilitating incurable illness.

Язык: Английский

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A real-world pharmacovigilance study of adverse drug reactions associated with lecanemab and aducanumab based on WHO-VigiAccess and FAERS databases

Frontiers in Pharmacology, Год журнала: 2025, Номер 16

Опубликована: Апрель 1, 2025

Background Lecanemab and Aducanumab are two novel anti-amyloid beta (Aβ) therapies for Alzheimer’s disease (AD) that have shown promise in slowing cognitive decline. However, their safety profiles remain unclear due to limited real-world evidence. This study aims analyze compare adverse drug reactions (ADRs) of these drugs using data from the WHO-VigiAccess FAERS databases. Methods A retrospective analysis was conducted ADR VigiAccess databases, focusing on System Organ Class (SOC) Preferred Term (PT) classifications. Descriptive statistics reporting odds ratio (ROR) were employed evaluate profiles. Results exhibited distinct ADRs. both databases indicated most SOC associated with nervous system disorders (34.7% VigiAccess, 36.8% FAERS). Further multivariable logistic regression revealed a higher risk (OR = 4.72, 95% CI: 3.53–6.39, P < 0.001). Among reported AEs, headache frequently (9.4% 8.96% FAERS), while primarily amyloid-related imaging abnormalities (ARIA) (19.1% 23.58% In blood lymphatic systems, Anemia observed drugs. thrombocyto-penia more prevalent Lecanemab, platelet dysfunction myelosuppression Aducanumab. Additionally, hospitalization mortality rates compared Lecanemab. Conclusion ADRs Aducanumab, revealing ARIA common AE showed lower ARIA, cerebral hemorrhage, severe events. These findings emphasize need further clinical research clarify long-term efficacy

Язык: Английский

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