Alzheimer's disease drug development pipeline: 2022

Alzheimer s & Dementia Translational Research & Clinical Interventions, Год журнала: 2022, Номер 8(1)

Опубликована: Янв. 1, 2022

Alzheimer's disease (AD) represents a global health crisis. Treatments are needed to prevent, delay the onset, slow progression, improve cognition, and reduce behavioral disturbances of AD. We review current clinical trials drugs in development for treatment

Язык: Английский

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The amyloid hypothesis in Alzheimer disease: new insights from new therapeutics

Nature Reviews Drug Discovery, Год журнала: 2022, Номер 21(4), С. 306 - 318

Опубликована: Фев. 17, 2022

Язык: Английский

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A Review of the Common Neurodegenerative Disorders: Current Therapeutic Approaches and the Potential Role of Nanotherapeutics

International Journal of Molecular Sciences, Год журнала: 2022, Номер 23(3), С. 1851 - 1851

Опубликована: Фев. 6, 2022

Neurodegenerative disorders are primarily characterized by neuron loss. The most common neurodegenerative include Alzheimer’s and Parkinson’s disease. Although there several medicines currently approved for managing disorders, a large majority of them only help with associated symptoms. This lack pathogenesis-targeting therapies is due to the restrictive effects blood–brain barrier (BBB), which keeps close 99% all “foreign substances” out brain. Since their discovery, nanoparticles have been successfully used targeted delivery into many organs, including review briefly describes pathophysiology Alzheimer’s, disease, amyotrophic lateral sclerosis, current management approaches. We then highlight major challenges brain-drug delivery, followed role nanotherapeutics diagnosis treatment various neurological disorders.

Язык: Английский

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Amyloid β-based therapy for Alzheimer’s disease: challenges, successes and future

Signal Transduction and Targeted Therapy, Год журнала: 2023, Номер 8(1)

Опубликована: Июнь 30, 2023

Abstract Amyloid β protein (Aβ) is the main component of neuritic plaques in Alzheimer’s disease (AD), and its accumulation has been considered as molecular driver pathogenesis progression. Aβ prime target for development AD therapy. However, repeated failures Aβ-targeted clinical trials have cast considerable doubt on amyloid cascade hypothesis whether drug followed correct course. recent successes targeted assuaged those doubts. In this review, we discussed evolution over last 30 years summarized application diagnosis modification. particular, extensively pitfalls, promises important unanswered questions regarding current anti-Aβ therapy, well strategies further study more feasible approaches optimization prevention treatment.

Язык: Английский

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Alzheimer's disease drug development pipeline: 2023

Alzheimer s & Dementia Translational Research & Clinical Interventions, Год журнала: 2023, Номер 9(2)

Опубликована: Апрель 1, 2023

Drugs that prevent the onset, slow progression, or improve cognitive and behavioral symptoms of Alzheimer's disease (AD) are needed.

Язык: Английский

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Potential disease-modifying therapies for Huntington's disease: lessons learned and future opportunities

The Lancet Neurology, Год журнала: 2022, Номер 21(7), С. 645 - 658

Опубликована: Июнь 15, 2022

Язык: Английский

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Microglia Phenotypes in Aging and Neurodegenerative Diseases

Cells, Год журнала: 2022, Номер 11(13), С. 2091 - 2091

Опубликована: Июнь 30, 2022

Neuroinflammation is a hallmark of many neurodegenerative diseases (NDs) and plays fundamental role in mediating the onset progression disease. Microglia, which function as first-line immune guardians central nervous system (CNS), are drivers neuroinflammation. Numerous human postmortem studies vivo imaging analyses have shown chronically activated microglia patients with various acute chronic neuropathological diseases. While microglial activation common feature NDs, exact pathological states complex often contradictory. However, there consensus that play biphasic conditions, detrimental protective phenotypes, overall response different phenotypes depends on nature duration inflammatory insult, well stage disease development. This review provides comprehensive overview current research responses health, aging, special emphasis heterogeneous phenotypic such hemorrhagic stroke (HS), Alzheimer's (AD), Parkinson's (PD). The primary focus translational preclinical animal models bulk/single-cell transcriptome samples. Additionally, this covers key receptors signaling pathways potential therapeutic targets to regulate during aging NDs. age-, sex-, species-specific differences will be briefly reviewed.

Язык: Английский

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Aducanumab: Appropriate Use Recommendations Update

The Journal of Prevention of Alzheimer s Disease, Год журнала: 2022, Номер unknown

Опубликована: Янв. 1, 2022

Aducanumab (Aduhelm) is approved in the United States for treatment of patients with mild cognitive impairment due to Alzheimer's disease or AD dementia. Appropriate Use Recommendations (AURs) have been published and helped guide best practices use aducanumab. As real-world has occurred more information accrued, AURs require refinement. We update better inform appropriate patient selection improve shared decision-making, safety monitoring, risk mitigation treated patients. Based on evolving experience we emphasize importance detecting past medical conditions that may predispose amyloid related imaging abnormalities (ARIA) increase likelihood ARIA complications including autoimmune inflammatory conditions, seizures, disorders associated extensive white matter pathology. The apolipoprotein E ε4 (APOE4) genotype strongly exhibits a gene dose effect. recommend clinicians perform APOE genotyping care decisions, discussions regarding risk, clinician vigilance concerning ARIA. most occurs during titration period aducanumab, suggest performing MRI before 5th, 7th, 9th, 12th infusions detection. Uncommonly, be recurrent serious; additional parameters discontinuation taking these observations into account. It important continue learn from aducanumab will evolve as new becomes available. This AUR does not address efficacy, price, insurance coverage provided assist establish

Язык: Английский

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Evaluating the Safety and Efficacy of Crenezumab vs Placebo in Adults With Early Alzheimer Disease

JAMA Neurology, Год журнала: 2022, Номер 79(11), С. 1113 - 1113

Опубликована: Сен. 19, 2022

Importance Alzheimer disease (AD), a neurodegenerative characterized by β-amyloid plaques and τ tangles in the brain, represents an unmet medical need with no fully approved therapeutics to modify progression. Objective To investigate safety efficacy of crenezumab, humanized monoclonal immunoglobulin G4 antibody targeting oligomers, participants prodromal mild (early) AD. Design, Setting, Participants Two phase 3 multicenter randomized double-blind placebo-controlled parallel-group studies crenezumab early AD, CREAD CREAD2, were initiated 2016 2017, respectively, designed evaluate (194 sites 30 countries) CREAD2 (209 27 global studies. A total 3736 3664 screened respectively. Both trials enrolled individuals aged 50 85 years some comorbidities evidence cerebral infarction or more than 4 microbleeds areas leptomeningeal hemosiderosis on magnetic resonance imaging excluded. After 2923 2858 excluded, 813 806 randomly assigned 1:1 ratio either placebo crenezumab. In final analysis, there 409 group 404 399 407 CREAD2. Data analyzed up until January 2019 August 2019, Interventions received 60 mg/kg intravenously every weeks for 100 weeks. Main Outcomes Measures The primary outcome was change from baseline week 105 Clinical Dementia Rating–Sum Boxes (CDR-SB) score. Results There (mean [SD] age, 70.7 [8.2] years; 483 female 330 male) 70.9 [7.7] 456 350 male). Baseline characteristics balanced between both groups. between-group difference mean CDR-SB score (placebo minus crenezumab) −0.17 (95% CI, −0.86 0.53; P = .63) at study (88 placebo; 86 crenezumab). Compared previous trials, new signals identified, amyloid-related abnormalities edema rare, mild, transient. No meaningful changes AD biomarkers observed. discontinued following preplanned interim analysis indicating that unlikely meet end point. Conclusions Relevance Crenezumab well tolerated but did not reduce clinical decline Trial Registration ClinicalTrials.gov Identifiers: CREAD, NCT02670083 ; NCT03114657

Язык: Английский

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Clinical trials of new drugs for Alzheimer disease: a 2020–2023 update

Journal of Biomedical Science, Год журнала: 2023, Номер 30(1)

Опубликована: Окт. 2, 2023

Abstract Alzheimer's disease (AD) is the leading cause of dementia, presenting a significant unmet medical need worldwide. The pathogenesis AD involves various pathophysiological events, including accumulation amyloid and tau, neuro-inflammation, neuronal injury. Clinical trials focusing on new drugs for were documented in 2020, but subsequent developments have emerged since then. Notably, US-FDA has approved Aducanumab Lecanemab, both antibodies targeting amyloid, marking end nearly two-decade period without drugs. In this comprehensive report, we review all listed clinicaltrials.gov, elucidating their underlying mechanisms study designs. Ongoing clinical are investigating numerous promising AD. main trends these involve pathophysiology-based, disease-modifying therapies recruitment participants earlier stages disease. These underscore significance conducting fundamental research pathophysiology, prevention, intervention prior to occurrence brain damage caused by

Язык: Английский

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