Anti-Amyloid Monoclonal Antibodies for the Treatment of Alzheimer’s Disease

BioDrugs, Год журнала: 2023, Номер 38(1), С. 5 - 22

Опубликована: Ноя. 13, 2023

Two monoclonal antibodies (mAbs), aducanumab and lecanemab, have received accelerated approval from the US FDA for initiation of treatment in early Alzheimer's disease patients who proven β-amyloid pathology (Aβ). One these, has subsequently full other are poised positive review approval. Anti-amyloid mAbs share feature producing a marked reduction total brain Aβ revealed by amyloid positron emission tomography. Trials associated with slowing cognitive decline achieved measurable plaque range 15–25 centiloids; trials agents that did not reach this threshold were benefit. differences terms titration schedules, MRI monitoring schedules amyloid-related imaging abnormalities (ARIA), continuing versus interrupted therapy. The approximate 30% observed is clinically meaningful extended integrity delay onset more severe dementia phases disease. Approval these initiates new era therapeutics disease-modifying properties. Further advances needed, i.e. greater efficacy, improved safety, enhanced convenience, better understanding ill-understood observations such as volume loss.

Язык: Английский

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Alzheimer's disease current therapies, novel drug delivery systems and future directions for better disease management

Journal of Controlled Release, Год журнала: 2024, Номер 367, С. 402 - 424

Опубликована: Фев. 2, 2024

Alzheimer's disease (AD), is a neurodegenerative disorder that escalates with time, exerting significant impact on physical and mental health leading to death. The prevalence of AD progressively rising along its associated economic burden necessitates effective therapeutic approaches in the near future. This review paper aims offer an insightful overview pathogenesis, current FDA-approved drugs, drugs different clinical phases. It also explores innovative formulations drug delivery strategies, focusing nanocarriers long-acting medications (LAMs) enhance treatment efficacy patient adherence. emphasizes preclinical evidence related their potential improve bioavailability, pharmacokinetics, pharmacodynamics parameters, while highlighting ability minimize systemic side effects. By providing comprehensive analysis, this furnishes valuable insights into pathophysiological mechanisms for future development. inform development strategies formulation delivering existing molecules disease, ultimately striving compliance.

Язык: Английский

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Alzheimer’s disease and its treatment–yesterday, today, and tomorrow

Frontiers in Pharmacology, Год журнала: 2024, Номер 15

Опубликована: Май 24, 2024

Alois Alzheimer described the first patient with Alzheimer’s disease (AD) in 1907 and today AD is most frequently diagnosed of dementias. a multi-factorial neurodegenerative disorder familial, life style comorbidity influences impacting global population more than 47 million projected escalation by 2050 to exceed 130 million. In USA demographic encompasses approximately six individuals, expected increase surpass 13 2050, antecedent phase AD, recognized as mild cognitive impairment (MCI), involves nearly 12 individuals. The economic outlay for management AD-related decline estimated at 355 billion USD. addition, intensifying prevalence cases countries modest intermediate income further enhances urgency therapeutically cost-effective treatments improving quality patients their families. This narrative review evaluates pathophysiological basis an initial focus on therapeutic efficacy limitations existing drugs that provide symptomatic relief: acetylcholinesterase inhibitors (AChEI) donepezil, galantamine, rivastigmine, N-methyl-D-aspartate receptor (NMDA) allosteric modulator, memantine. hypothesis amyloid-β (Aβ) tau are appropriate targets have potential halt progress critically analyzed particular clinical trial data anti-Aβ monoclonal antibodies (MABs), namely, aducanumab, lecanemab donanemab. challenges dogma targeting Aβ will benefit majority subjects MABs unlikely be “magic bullet”. A comparison benefits disadvantages different classes forms determining new directions research alternative drug undergoing pre-clinical assessments. we discuss stress importance treatment co-morbidities, including hypertension, diabetes, obesity depression known risk developing AD.

Язык: Английский

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Maximizing the benefit and managing the risk of anti-amyloid monoclonal antibody therapy for Alzheimer's disease: Strategies and research directions

Neurotherapeutics, Год журнала: 2025, Номер unknown, С. e00570 - e00570

Опубликована: Март 1, 2025

Язык: Английский

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Pathogenesis, Diagnostics, and Therapeutics for Alzheimer's Disease: Breaking the Memory Barrier

Ageing Research Reviews, Год журнала: 2024, Номер 101, С. 102481 - 102481

Опубликована: Сен. 3, 2024

Alzheimer's disease (AD) is the most common cause of dementia and accounts for 60-70 % all cases. It affects millions people worldwide. AD poses a substantial economic burden on societies healthcare systems. progressive neurodegenerative disorder characterized by cognitive decline, memory loss, impaired daily functioning. As prevalence continues to increase, understanding its pathogenesis, improving diagnostic methods, developing effective therapeutics have become paramount. This comprehensive review delves into intricate mechanisms underlying AD, explores current state techniques, examines emerging therapeutic strategies. By revealing complexities this aims contribute growing body knowledge surrounding devastating disease.

Язык: Английский

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Ginkgo biloba: A Leaf of Hope in the Fight Against Alzheimer’s Dementia: Clinical Trial Systematic Review

Опубликована: Апрель 12, 2024

Alzheimer's disease (AD) is a stealthy and progressive neurological disorder that leading cause of dementia in the global elderly population, imposing significant burden on both society. Currently, condition treated with medications alleviate symptoms. Nonetheless, these drugs may not consistently produce desired results can serious side effects. Hence, there vigorous pursuit alternative options to enhance quality life for patients. Ginkgo biloba (GB), an herb historical use traditional medicine, contains bioactive compounds such as terpenoids (Ginkgolides A, B, C), polyphenols, organic acids, flavonoids (quercetin, kaempferol, isorhamnetin). These are associated anti-inflammatory, antioxidant, neuroprotective properties, making them valuable cognitive health. A systematic search across three databases using specific keywords GB AD yielded 1702 documents, selection 15 clinical trials synthesis. In eleven studies, extract/EGb 761® was shown improve function, neuropsychiatric symptoms, functional abilities types. four however, were no differences between GB-treated placebo groups. Significant improvements observed scores obtained from Mini-Mental State Examination (MMSE), Short Cognitive Performance Test (SKT), Neuropsychiatric Inventory (NPI). While majority synthesized show has promising potential conditions, more research needed determine optimal dosages, effective delivery methods, appropriate pharmaceutical formulations. Furthermore, thorough assessment adverse effects, exploration long-term implications, investigation into drug interactions critical aspects must be carefully evaluated future studies.

Язык: Английский

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Novel 6-alkyl-bridged 4-arylalkylpiperazin-1-yl derivatives of azepino[4,3-b]indol-1(2H)-one as potent BChE-selective inhibitors showing protective effects against neurodegenerative insults

European Journal of Medicinal Chemistry, Год журнала: 2024, Номер 270, С. 116353 - 116353

Опубликована: Март 20, 2024

Due to the putative role of butyrylcholinesterase (BChE) in regulation acetylcholine levels and functions late stages Alzheimer's disease (AD), potential selective inhibitors (BChEIs) has been envisaged as an alternative administration acetylcholinesterase (AChEIs). Starting from our recent findings, herein synthesis vitro evaluation cholinesterase (ChE) inhibition a novel series some twenty 3,4,5,6-tetrahydroazepino[4,3-b]indol-1(2H)-one derivatives, bearing at indole nitrogen diverse alkyl-bridged 4-arylalkylpiperazin-1-yl chains, are reported. The length spacers, well type arylalkyl group affected enzyme potency BChE/AChE selectivity. Two compounds, namely 14c (IC50 = 163 nM) 14d 65 nM), atom position 6 n-pentyl- or n-heptyl-bridged 4-phenethylpiperazin-1-yl respectively, proved be highly potent mixed-type both equine human BChE isoforms, showing more than two order magnitude selectivity over AChE. study binding kinetics through surface plasmon resonance (SPR) highlighted differences their residence times (8 47 s for 14d, respectively). Moreover, hit other mechanisms known trigger neurodegeneration underlying AD CNS disorders. Unlike 14c, compound also capable inhibiting by 60% self-induced aggregation neurotoxic amyloid-β (Aβ) peptide 100 μM concentration. On hand, was slightly better counteracting, 1 10 concentration, glutamate excitotoxicity, due over-excitation NMDA receptors, hydrogen peroxide-induced oxidative stress assessed neuroblastoma cell line SH-SY5Y.

Язык: Английский

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Ginkgo biloba: A Leaf of Hope in the Fight against Alzheimer’s Dementia: Clinical Trial Systematic Review

Antioxidants, Год журнала: 2024, Номер 13(6), С. 651 - 651

Опубликована: Май 27, 2024

Alzheimer’s disease (AD) is a stealthy and progressive neurological disorder that leading cause of dementia in the global elderly population, imposing significant burden on both society. Currently, condition treated with medications alleviate symptoms. Nonetheless, these drugs may not consistently produce desired results can serious side effects. Hence, there vigorous pursuit alternative options to enhance quality life for patients. Ginkgo biloba (GB), an herb historical use traditional medicine, contains bioactive compounds such as terpenoids (Ginkgolides A, B, C), polyphenols, organic acids, flavonoids (quercetin, kaempferol, isorhamnetin). These are associated anti-inflammatory, antioxidant, neuroprotective properties, making them valuable cognitive health. A systematic search across three databases using specific keywords—GB AD dementia—yielded 1702 documents, selection 15 clinical trials synthesis. In eleven studies, GB extract/EGb 761® was shown improve function, neuropsychiatric symptoms, functional abilities types. four however, were no differences between GB-treated placebo groups. Significant improvements observed scores obtained from Mini-Mental State Examination (MMSE), Short Cognitive Performance Test (SKT), Neuropsychiatric Inventory (NPI). While majority synthesized show has promising potential treatment conditions, more research needed determine optimal dosages, effective delivery methods, appropriate pharmaceutical formulations. Furthermore, thorough assessment adverse effects, exploration long-term implications, investigation into drug interactions critical aspects must be carefully evaluated future studies.

Язык: Английский

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Targeting the NRF2 pathway for disease modification in neurodegenerative diseases: mechanisms and therapeutic implications

Frontiers in Pharmacology, Год журнала: 2024, Номер 15

Опубликована: Июль 25, 2024

Neurodegenerative diseases constitute a global health issue and major economic burden. They significantly impair both cognitive motor functions, their prevalence is expected to rise due ageing societies continuous population growth. Conventional therapies provide symptomatic relief, nevertheless, disease-modifying treatments that reduce or halt neuron death malfunction are still largely unavailable. Amongst the common hallmarks of neurodegenerative protein aggregation, oxidative stress, neuroinflammation mitochondrial dysfunction. Transcription factor nuclear factor-erythroid 2-related 2 (NRF2) constitutes central regulator cellular defense mechanisms, including regulation antioxidant, anti-inflammatory pathways, making it highly attractive therapeutic target for disease modification in disorders. Here, we describe role NRF2 neurodegeneration, review current pharmacological interventions challenges activating pathway, present alternative approaches modification.

Язык: Английский

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Targeting the molecular web of Alzheimer’s disease: unveiling pathways for effective pharmacotherapy

The Egyptian Journal of Neurology Psychiatry and Neurosurgery, Год журнала: 2024, Номер 60(1)

Опубликована: Янв. 11, 2024

Abstract Introduction Alzheimer’s disease is a neurocognitive disorder that affects elderly people by slowly impaired cognition, dementia, and gets worse with age. It impacts the quality of life. Clinically, it distinguished transition from episodic memory to gradual reduction in cognitive ability leading dysfunction. Neurofibrillary tangles amyloid plaques are unique structures thought have role pathogenesis Alzheimer's disease. In this review, we focus our attention on risk factors, pathophysiology, etiology, epidemiology, stages, diagnosis, treatment, mechanisms, pathways, ongoing clinical trials data risks potentially associated development Short summary This review aims extrapolate information about Preliminary research was done selecting reviews PubMed, Elsevier, Google open-access publications using keywords like “Alzheimer, neurodegenerative, memory, β, mechanism action, pathways”. Conclusion Here show discussion interpretation several signaling pathways such as β plaque cleavage, Metal ion hypothesis, degradation, initiation amyloidogenic non-amyloidogenic pathway, oxidative stress Metabolic syndrome, insulin resistance tau phosphorylation apolipoprotein- cholesterol, neurofibrillary accumulation, which significant for better understanding progression. On studying trials, found current drugs being tested crenezumab, gantenerumab sodium oligonucleotide. Graphical

Язык: Английский

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