New Possibilities in the Therapeutic Approach to Alzheimer’s Disease DOI Open Access
Julia Doroszkiewicz, Barbara Mroczko

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(16), P. 8902 - 8902

Published: Aug. 10, 2022

Despite the fact that Alzheimer's disease (AD) is most common cause of dementia, after many years research regarding this disease, there no casual treatment. Regardless serious public health threat it poses, only five medical treatments for have been authorized, and they control symptoms rather than changing course disease. Numerous clinical trials single-agent therapy did not slow development or improve when compared to placebo. Evidence indicates pathological alterations linked AD start earlier a manifestation In pre-clinical period before neurodegenerative process established, pharmaceutical might prove invaluable. Although recent findings from testing drugs such as aducanumab are encouraging, should nevertheless be interpreted cautiously. Such medications may able delay onset significantly lowering prevalence but still long way having clinically effective disease-modifying therapy.

Language: Английский

Aducanumab for the treatment of Alzheimer's disease: a systematic review DOI Creative Commons

Afroza Rahman,

Md. Anwar Hossen,

Mirza Farhana Iqbal Chowdhury

et al.

Psychogeriatrics, Journal Year: 2023, Volume and Issue: 23(3), P. 512 - 522

Published: Feb. 12, 2023

Aducanumab is a novel disease‐modifying anti‐amyloid‐beta (Aβ) human monoclonal antibody specifically targeted to the pathophysiology of Alzheimer's disease (AD). It was granted for treating AD in June 2021 by United States Food and Drug Administration. We systematically analyzed available trials evaluate efficacy safety aducanumab AD. followed PRISMA (Preferred Reporting Items Systematic Reviews Meta‐Analysis) guidelines. conducted an extensive literature search using electronic databases MEDLINE through PubMed, EMBASE, Cochrane, Web Science, Scopus suitable studies on aducanumab. considered clinical aducanumab, assessing its adverse effects AD, excluding any experimental animal studies. included three randomised controlled trials. Studies reported that reduced brain amyloid‐beta plaques time‐ dose‐dependent manner (dose–response, P < 0.05) slowed decline cognition (22% reduction) high‐dose treated group, difference −0.39 versus placebo Clinical Dementia Rating Scale Sum Boxes (95% CI, −0.69 −0.09; = 0.012) along with amyloid positron emission tomography standard uptake value ratio score ( 0.001) plasma p181‐tau (phosphorylated tau) level. Amyloid‐related imaging abnormality as serious event profound group (425/1029 10 mg/kg). has been affect two main pathophysiologic hallmarks (Aβ suggest future addressing aducanumab's confirm benefit this drug outweighs risk.

Language: Английский

Citations

61
Alzheimer's disease current therapies, novel drug delivery systems and future directions for better disease management DOI Creative Commons
Baljinder Singh, Candace M. Day, Sadikalmahdi Abdella

et al.

Journal of Controlled Release, Journal Year: 2024, Volume and Issue: 367, P. 402 - 424

Published: Feb. 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.

Language: Английский

Citations

61
Treatment of Alzheimer’s Disease: Beyond Symptomatic Therapies DOI Open Access

Francesca R. Buccellato,

Marianna D’Anca, Gianluca Martino Tartaglia

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(18), P. 13900 - 13900

Published: Sept. 9, 2023

In an ever-increasing aged world, Alzheimer’s disease (AD) represents the first cause of dementia and one chronic diseases in elderly people. With 55 million people affected, WHO considers AD to be a with public priority. Unfortunately, there are no final cures for this pathology. Treatment strategies aimed mitigate symptoms, i.e., acetylcholinesterase inhibitors (AChEI) N-Methyl-D-aspartate (NMDA) antagonist Memantine. At present, best approaches managing seem combine pharmacological non-pharmacological therapies stimulate cognitive reserve. Over last twenty years, number drugs have been discovered acting on well-established biological hallmarks AD, deposition β-amyloid aggregates accumulation hyperphosphorylated tau protein cells. Although previous efforts disappointed expectations, new era treating has working its way recently. The Food Drug Administration (FDA) gave conditional approval disease-modifying therapy (DMT) treatment aducanumab, monoclonal antibody (mAb) designed against Aβ plaques oligomers 2021, January 2023, FDA granted accelerated second antibody, Lecanemab. This review describes ongoing clinical trials DMTs therapies. We will also present future scenario based biomarkers that can detect preclinical or prodromal stages, identify at risk developing allow early curative treatment.

Language: Английский

Citations

52
Basic information about memantine and its treatment of Alzheimer's disease and other clinical applications DOI Creative Commons
Bin‐Can Tang, Ya‐Ting Wang, Jie Ren

et al.

Ibrain, Journal Year: 2023, Volume and Issue: 9(3), P. 340 - 348

Published: June 6, 2023

Memantine is a noncompetitive moderate-affinity strong voltage-dependent N-methyl-D-aspartate receptor antagonist. It has been used to treat Alzheimer's disease (AD) since 1989. In 2018, it became the second most commonly drug for treatment of dementia in world. AD nonreversible, and memantine can only relieve symptoms but not cure it. Over past half-century, memantine's research clinical application have extensively developed. this review, basic composition memantine, mechanism limitations AD, combination therapy, comparison with other drugs studies diseases are reviewed provide valuable reference further AD.

Language: Английский

Citations

46
Risk factors in developing amyloid related imaging abnormalities (ARIA) and clinical implications DOI Creative Commons
Sarah J. Doran, Russell P. Sawyer

Frontiers in Neuroscience, Journal Year: 2024, Volume and Issue: 18

Published: Jan. 19, 2024

Alzheimer’s disease (AD) affects over 6 million people the age of 65. The advent new anti-amyloid monoclonal antibodies as treatment for early these immunotherapeutics may slow progression but also pose significant risks. Amyloid related imaging abnormalities (ARIA) identified on MRI following administration can cause both brain edema (ARIA-E) and hemorrhage (ARIA-H). While most ARIA is asymptomatic, some patients develop headache, confusion, nausea, dizziness, seizures in rare cases death. By analyzing lecanemab, aducanumab, gantenerumab, donanemab, bapineuzumab clinical trials; risk factors developing be to mitigate risk. Risk ARIA-E are a positive Apoε4 carrier status prior multiple cerebral microhemorrhages. ARIA-H age, antithrombotic use, history strokes. With were seen at lower rates 12 17%, respectively, compared aducanumab (ARIA-E 35% 19%) treated patients. have impacted inclusion exclusion criteria, determining who receive lecanemab. In clinics, almost 90% excluded from receiving therapeutics. This review aims discuss highlight important areas further research. more approved by Food Drug Administration, considering patient identify minimize patient’s while therapies.

Language: Английский

Citations

34
Review on anti-alzheimer drug development: approaches, challenges and perspectives DOI Creative Commons
Abdallah E. Abdallah

RSC Advances, Journal Year: 2024, Volume and Issue: 14(16), P. 11057 - 11088

Published: Jan. 1, 2024

Alzheimer has many crucial factors that should be considered in order to get better results from clinical trials. Benzimidazole and its isosteres represent significant scaffolds for designing potential multi-target anti-alzheimer molecules.

Language: Английский

Citations

22
Linking the Amyloid, Tau, and Mitochondrial Hypotheses of Alzheimer’s Disease and Identifying Promising Drug Targets DOI Creative Commons
Zdeněk Fišar

Biomolecules, Journal Year: 2022, Volume and Issue: 12(11), P. 1676 - 1676

Published: Nov. 11, 2022

Damage or loss of brain cells and impaired neurochemistry, neurogenesis, synaptic nonsynaptic plasticity the lead to dementia in neurodegenerative diseases, such as Alzheimer's disease (AD). Injury synapses neurons accumulation extracellular amyloid plaques intracellular neurofibrillary tangles are considered main morphological neuropathological features AD. Age, genetic epigenetic factors, environmental stressors, lifestyle contribute risk AD onset progression. These factors associated with structural functional changes brain, leading cognitive decline. Biomarkers reflect cause specific function, especially pathways neurotransmission, neuroinflammation, bioenergetics, apoptosis, oxidative nitrosative stress. Even initial stages, is Aβ neurotoxicity, mitochondrial dysfunction, tau neurotoxicity. The integrative amyloid-tau-mitochondrial hypothesis assumes that primary neurotoxicity oligomers oligomers, their mutual synergy. For development new efficient drugs, targeting elimination potentiation effects, unwanted protein interactions biomarkers (mainly dysfunction) early stage seems promising.

Language: Английский

Citations

54
Anti-Amyloid Therapies for Alzheimer’s Disease and the Amyloid Cascade Hypothesis DOI Open Access
Ernesto Fedele

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(19), P. 14499 - 14499

Published: Sept. 24, 2023

Over the past 30 years, majority of (pre)clinical efforts to find an effective therapy for Alzheimer’s disease (AD) focused on clearing β-amyloid peptide (Aβ) from brain since, according amyloid cascade hypothesis, was (and it is still considered by many) pathogenic determinant this neurodegenerative disorder. However, as reviewed in article, results numerous clinical trials that have tested anti-Aβ therapies date indicate plays a minor role pathogenesis AD. Indeed, even Aducanumab and Lecanemab, two antibodies recently approved FDA AD therapy, well Donanemab showed limited efficacy cognitive parameters phase III trials, despite their capability markedly lowering Aβ load. Furthermore, preclinical evidence demonstrates possesses several physiological functions, including memory formation, suggesting may part be due loss function peptide. Finally, generally accepted could result many molecular dysfunctions, therefore, if we keep chasing only Aβ, means cannot see forest trees.

Language: Английский

Citations

40
Antibody-Mediated Clearance of Brain Amyloid-β: Mechanisms of Action, Effects of Natural and Monoclonal Anti-Aβ Antibodies, and Downstream Effects DOI Creative Commons
David A. Loeffler

Journal of Alzheimer s Disease Reports, Journal Year: 2023, Volume and Issue: 7(1), P. 873 - 899

Published: Aug. 7, 2023

Immunotherapeutic efforts to slow the clinical progression of Alzheimer’s disease (AD) by lowering brain amyloid-β (Aβ) have included Aβ vaccination, intravenous immunoglobulin (IVIG) products, and anti-Aβ monoclonal antibodies. Neither vaccination nor IVIG slowed progression. Despite conflicting phase III results, antibody Aducanumab received Food Drug Administration (FDA) approval for treatment AD in June 2021. The only treatments unequivocally demonstrated date are antibodies Lecanemab Donanemab. FDA January 2023 based on II results showing PET-detectable Aβ; released at that time indicated slowing Topline May Donanemab’s trial revealed primary secondary end points had been met. Antibody binding facilitates its clearance from via multiple mechanisms including promoting microglial phagocytosis, activating complement, dissolving fibrillar Aβ, antibody-Aβ complexes blood-brain barrier receptors. peripheral blood may also promote cerebral efflux a sink mechanism. According amyloid hypothesis, targeting progression, it must decrease downstream neuropathological processes tau aggregation phosphorylation (possibly) inflammation oxidative stress. This review discusses antibody-mediated clearance, findings trials involving IVIG, antibodies, effects reported those trials, approaches which might improve Aβ-clearing ability

Language: Английский

Citations

36
Intranasal Drug Delivery by Nanotechnology: Advances in and Challenges for Alzheimer’s Disease Management DOI Creative Commons
Sayali Dighe, Sunil Jog, Munira Momin

et al.

Pharmaceutics, Journal Year: 2023, Volume and Issue: 16(1), P. 58 - 58

Published: Dec. 29, 2023

Alzheimer's disease, a progressive neurodegenerative condition, is characterized by gradual decline in cognitive functions. Current treatment approaches primarily involve the administration of medications through oral, parenteral, and transdermal routes, aiming to improve function alleviate symptoms. However, these treatments face limitations, such as low bioavailability inadequate permeation. Alternative invasive methods, while explored, often entail discomfort require specialized assistance. Therefore, development non-invasive efficient delivery system crucial. Intranasal has emerged potential solution, although it constrained unique conditions nasal cavity. An innovative approach involves use nano-carriers based on nanotechnology for intranasal delivery. This strategy overcome current limitations providing enhanced bioavailability, improved permeation, effective traversal blood-brain barrier, extended retention within body, precise targeting brain. The comprehensive review focuses advancements designing various types nano-carriers, including polymeric nanoparticles, metal lipid liposomes, nanoemulsions, Quantum dots, dendrimers. These are specifically tailored therapeutic agents aimed at combatting disease. In summary, utilization systems show significant surmounting constraints disease strategies. Nevertheless, essential acknowledge regulatory well toxicity concerns associated with this route; meticulous consideration required when engineering carrier. underscores revolutionize management highlights importance addressing considerations safe implementations. Embracing could lead substantial field treatment.

Language: Английский

Citations

26