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

BioDrugs, Journal Year: 2023, Volume and Issue: 38(1), P. 5 - 22

Published: Nov. 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.

Language: Английский

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Aducanumab—Hope or Disappointment for Alzheimer’s Disease

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(5), P. 4367 - 4367

Published: Feb. 22, 2023

In June 2021, the world was informed about a new drug for Alzheimer’s disease approved by FDA. Aducanumab (BIIB037, ADU), being monoclonal antibody IgG1, is newest AD treatment. The activity of targeted towards amyloid β, which considered one main causes disease. Clinical trials have revealed time- and dose-dependent Aβ reduction, as well cognition improvement. Biogen, company responsible conducting research introducing to market, presents solution cognitive impairment, but its limitations, costs, side effects are controversial. framework paper focuses on mechanism aducanumab’s action along with positive negative sides therapy. review basis hypothesis that cornerstone therapy, latest information aducanumab, action, possibility use drug.

Language: Английский

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Understanding neuropsychiatric symptoms in Alzheimer’s disease: challenges and advances in diagnosis and treatment

Frontiers in Neuroscience, Journal Year: 2023, Volume and Issue: 17

Published: Sept. 5, 2023

Neuropsychiatric symptoms (NPS) in Alzheimer's disease (AD) affect up to 97% of AD patients, with an estimated 80% current patients experiencing these symptoms. Common AD-associated NPS include depression, anxiety, agitation, aggression, and apathy. The severity is typically linked the disease's progression extent cognitive decline. Additionally, are responsible for a significant increase morbidity, mortality, caregiver burden, earlier nursing home placement, greater healthcare expenditure. Despite their high prevalence impact, there notable lack clinical research on AD. In this article, we explore analyze prevalence, symptom manifestations, challenges diagnosis, treatment options associated Our literature review reveals that distinguishing accurately diagnosing remains challenging task settings. It often difficult discern whether secondary pathophysiological changes from or comorbid psychiatric conditions. Furthermore, availability effective pharmaceutical interventions, as well non-pharmacotherapies AD, limited. By highlighting advance diagnosis NPS, aspire offer new insights into complexity identifying treating within context contribute deeper understanding multifaceted nature

Language: Английский

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Neuroinflammation in Neurodegenerative Disorders: Current Knowledge and Therapeutic Implications

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(7), P. 3995 - 3995

Published: April 3, 2024

Neurodegenerative disorders (NDs) have become increasingly common during the past three decades. Approximately 15% of total population world is affected by some form NDs, resulting in physical and cognitive disability. The most NDs include Alzheimer’s disease, Parkinson’s amyotrophic lateral sclerosis, Huntington’s disease. Although are caused a complex interaction genetic, environmental, lifestyle variables, neuroinflammation known to be associated with all often leading permanent damage neurons central nervous system. Furthermore, numerous emerging pieces evidence demonstrated that inflammation not only supports progression but can also serve as an initiator. Hence, various medicines capable preventing or reducing been investigated ND treatments. While anti-inflammatory medicine has shown promising benefits several preclinical models, clinical outcomes questionable. In this review, we discuss their current treatment strategies, role pathophysiology use agents potential therapeutic option.

Language: Английский

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

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: May 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.

Language: Английский

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Evolving therapeutic interventions for the management and treatment of Alzheimer’s disease

Ageing Research Reviews, Journal Year: 2024, Volume and Issue: 95, P. 102229 - 102229

Published: Feb. 15, 2024

Language: Английский

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Guidelines for pharmacotherapy in Alzheimer’s disease – A primer on FDA-approved drugs

Journal of Neurosciences in Rural Practice, Journal Year: 2023, Volume and Issue: 14, P. 566 - 573

Published: Oct. 7, 2023

The growing prevalence of dementia makes it important for us to better understand its pathophysiology and treatment modalities, improve the quality life patients caregivers. Alzheimer’s disease (AD), a neurodegenerative disease, is most common form amnestic in geriatric population. Pathophysiology AD widely attributed aggregation amyloid-beta (Aβ) plaques hyperphosphorylation tau proteins. Initial modalities aimed increase brain perfusion non-specific manner. Subsequent therapy focused on rectifying neurotransmitter imbalance brain. Newer drugs modify progression by acting against aggregated Aβ plaques. However, not all used have been granted approval United States Food Drug Administration (FDA). This review categorizes summarizes FDA-approved manner that would make convenient reference researchers practicing physicians alike. Drugs mitigate symptoms may be categorized into mitigators Behavioral Psychological Symptoms Dementia (BPSD), cognitive decline. BPSD include brexpiprazole, an atypical antipsychotic with once-daily dosage suited treat agitation patients, suvorexant, orexin receptor antagonist sleep disturbances. Cognitive decline cholinesterase inhibitors such as donepezil, rivastigmine, galantamine glutamate memantine. Donepezil commonly prescribed drug. It cheap, well-tolerated, orally once daily, or transdermal patch weekly. increases ACh levels, enhances oligodendrocyte differentiation also protects toxicity. regular cardiac monitoring required due reports conduction side effects. Rivastigmine requires twice-daily oral replacement patch. has fewer effects than but local application-site reactions noted. Galantamine, addition improving short span time, delays development BPSDs minimal drug-drug interactions virtue having multiple metabolic pathways. disturbances must closely monitored for. Memantine, regulator, acts anti-Parkinsonian agent antidepressant, cognition neuroprotection, immediate-release sustained-release tablets. Disease-modifying aducanumab lecanemab reduce burden. Both act binding fibrillary conformations These risk causing amyloid-related imaging abnormalities, especially persons ApoE4 gene. Aducanumab administered every 4 weeks 2 weeks. decision choice drug made after considering availability drug, compliance patient (once-daily vs. doses daily), cost, specific comorbidities, risk-benefit ratio particular patient. Other non-pharmacological adopted holistic approach toward AD.

Language: Английский

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

Ageing Research Reviews, Journal Year: 2024, Volume and Issue: 101, P. 102481 - 102481

Published: Sept. 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.

Language: Английский

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Nanotechnology-Driven Therapeutic Innovations in Neurodegenerative Disorders: A Focus on Alzheimer’s and Parkinson’s Disease

Future Pharmacology, Journal Year: 2024, Volume and Issue: 4(2), P. 352 - 379

Published: April 30, 2024

Neurodegenerative disorders entail a progressive loss of neurons in cerebral and peripheral tissues, coupled with the aggregation proteins exhibiting altered physicochemical properties. Crucial to these conditions is gradual degradation central nervous system, manifesting as impairments mobility, aberrant behaviors, cognitive deficits. Mechanisms such proteotoxic stress, neuroinflammation, oxidative programmed cell death contribute ongoing dysfunction demise neurons. Presently, neurodegenerative diseases lack definitive cures, available therapies primarily offer palliative relief. The integration nanotechnology into medical practices has significantly augmented both treatment efficacy diagnostic capabilities. Nanoparticles, capable traversing blood–brain barrier, hold considerable potential for diagnosing treating brain pathologies. By combining gene therapy nanotechnology, therapeutic effectiveness against can be substantially enhanced. Recent advancements nano-biomaterial-based methodologies have fortified existing approaches neural stem (NSC) differentiation therapies. NSC-targeting technologies promising, potentially safe method diseases. This review endeavors summarize current insights perspectives on nanotechnology-driven innovations disorders, particular emphasis Alzheimer’s Parkinson’s disease.

Language: Английский

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Unraveling Alzheimer’s: the promise of aducanumab, lecanemab, and donanemab

The Egyptian Journal of Neurology Psychiatry and Neurosurgery, Journal Year: 2024, Volume and Issue: 60(1)

Published: June 14, 2024

Abstract Alzheimer’s disease (AD) is a neurodegenerative condition that causes cognitive decline, memory loss, and reduced personal autonomy. The pathology of AD involves the aggregation abnormal brain proteins, specifically beta-amyloid plaques tau tangles, disrupting neuronal communication leading to loss cells. Aducanumab, monoclonal antibody, demonstrates promise in clinical trials by selectively binding aggregated amyloid-beta, notable decrease plaque burden potential benefits. However, regulatory approval for aducanumab remains controversial. Lecanemab donanemab are recent additions AD’s treatment landscape, both targeting amyloid-beta. shares similarities with its mechanism action, while employs distinct approach specific truncated form Positive outcomes have been observed early-stage drugs, demonstrating reduction amyloid-beta plaques. While aducanumab’s offers hope treatment, ongoing studies on lecanemab imperative comprehensive understanding their modification. Here, we show this review treatments, focus primary action ultimately giving broader insight topic. emphasizes necessity long-term efficacy safety data assess overall impact these drugs decline functional future researchers endeavor. In conclusion, development antibodies represents significant stride demanding further investigation ascertain true role therapeutic arsenal challenging condition.

Language: Английский

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