Aducanumab: A new hope in Alzheimer's disease

Ali, Rouchan; Gupta, Ghanshyam Das; Chawla, Pooja

doi:10.1016/j.hsr.2022.100039

Cited by 12 publications

(11 citation statements)

References 100 publications

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“…The new treatment options represented by monoclonal antibodies may be a response to the severe impairment that AD carries but seeing that the trials were incomplete, those new molecules gather a lot of uncertainty from specialists. Outside of the US, there are no approvals for administering antibodies as treatment for AD, which raises a sceptical attitude among healthcare professionals [9][10][11].…”

Section: Resultsmentioning

confidence: 99%

Monoclonal antibodies treatment for Alzheimer’s dementia – a literature review

Horosan¹,

Nistor²,

Zaharia³

2021

Ro J Psychiatry Psychother.

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Alzheimer’s disease (AD), recognized by the World Health Organization (WHO) as one of the leading causes of death and disability among older people globally, is the most common form of dementia. The accumulation of amyloid plaques and neurofibrillary tangles in the brain leads to synaptic and neuronal loss, causing cognitive impairment and functional decline. Current treatment options, such as cholinesterase inhibitors and NMDA receptor antagonists, provide partial symptomatic relief but do not alter disease progression. Monoclonal antibodies targeting amyloid-β (Aβ) have emerged as potential disease-modifying therapies by promoting the clearance of Aβ plaques. This paper reviews recent scientific literature and ongoing clinical trials related to monoclonal antibody treatments for AD. Aducanumab, Bapineuzumab, Gantenerumab, Lecanemab, and Solanezumab are among the most discussed monoclonal antibodies. Aducanumab, which has received accelerated approval from the FDA, demonstrates efficacy in reducing Aβ plaques but has generated controversy due to differing opinions among regulatory agencies. Adverse reactions, particularly amyloid-related imaging abnormalities (ARIA), are associated with monoclonal antibody treatment. However, more extensive trials are required to establish their long-term safety and efficacy. Overall, monoclonal antibodies represent a potential breakthrough in AD treatment, although their use outside the US remains uncertain. Ongoing research and clinical trials are essential for further understanding and validating the efficacy and safety of these novel therapies.

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Section: Resultsmentioning

confidence: 99%

Monoclonal antibodies treatment for Alzheimer’s dementia – a literature review

Horosan¹,

Nistor²,

Zaharia³

2021

Ro J Psychiatry Psychother.

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“…As a result, tau protein begins to misfold and aggregate within the neuron, eventually forming neurofibrillary tangles (NFTs) inside neurons. These tangles not only interfere with the regions involved in memory tasks but also inhibit the transport system, gradually damaging the synaptic connections between neurons [5].…”

Section: Pathophysiology Of Admentioning

confidence: 99%

“…Typically, ARIA-E is characterized by brain swelling, which can lead to increased pressure inside the skull and potential neurological symptoms of headaches or confusion; whilst ARIA-H refers to small areas of bleeding in the brain. During the clinical trials, adverse effects were reported among patients, with 41% aducanumab-treated participants experiencing either ARIA-E or ARIA-H on imaging, compared to a 10% figure for placebo-administrated subjects [5]. The bulk of ARIA occurrences were recorded following the first eight doses of aducanumab's titration.…”

Section: Potential Disadvantages Of Aducanumabmentioning

confidence: 99%

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A new era in Alzheimer’s disease management: exploring aducanumab’s potential

Jiang

2024

Third International Conference on Biological Engineering and Medical Science (ICBioMed2023)

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Alzheimer's disease (AD) is a deadly neurological condition associated with symptoms of memory loss and progressive cognitive deterioration. As an age-related disorder, it has been challenging the medical departments globally, leading to profound social and economic implications. Although its pathogenesis is not fully understood, many scientists have reached a consensus on the relationship between amyloid-beta protein peptide accumulation and cognitive decline. Aducanumab, an innovative monoclonal antibody treatment, targets the aggregated plaques and seeks to promote clearance to delay disease progression. Unlike conventional medications, aducanumab is the first therapy that allows for direct binding with amyloidogenic agents and, theoretically, leads to the activation of the immune system. In this review, the author provides an overview of Aducanumab's mechanism and potential disadvantages, highlighting its critical role in slowing disease progression and emphasizing the controversy surrounding the accelerated approval. This paper also introduces investigational therapies that offer promising avenues offering hope for improved AD treatments and better quality of life for those affected. By revealing Aducanumab's journey from research laboratories to the clinic, the global medical community can better understand the pathophysiology of AD, which further pave the way for a more comprehensive approach to managing this devastating neurological condition in the future.

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“…Currently, the main approved AD therapy has been focused on increasing cholinergic transmission via the accumulation of ACh in the neuronal synaptic cleft, by inhibiting acetylcholinesterase (AChE). , At present, with the exception of memantine, all FDA-approved drugs such as donepezil, rivastigmine, and galantamine are AChE inhibitors (AChEIs) . The crystal structure of AChE shows that it consists of two binding sites: one is a catalytic anionic site (CAS) and the other is a peripheral anionic site (PAS), which are connected by a 20 Å deep gorge .…”

Section: Introductionmentioning

confidence: 99%

Modified Tacrine Derivatives as Multitarget-Directed Ligands for the Treatment of Alzheimer’s Disease: Synthesis, Biological Evaluation, and Molecular Modeling Study

et al. 2023

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To develop multitarget-directed ligands (MTDLs) as potential treatments for Alzheimer's disease (AD) and to shed light on the effect of the chromene group in designing these ligands, 35 new tacrinechromene derivatives were designed, synthesized, and biologically evaluated. Compounds 5c and 5d exhibited the most desirable multiple functions for AD; they were strong hAChE inhibitors with IC 50 values of 0.44 and 0.25 μM, respectively. Besides, their potent BuChE inhibitory activity was 10-and 5-fold more active than rivastigmine with IC 50 = 0.08 and 0.14 μM, respectively. Moreover, they could bind to the peripheral anionic site (PAS), influencing Aβ aggregation and decreasing Aβ-related neurodegeneration, especially compound 5d, which was 8 times more effective than curcumin with IC 50 = 0.74 μM and 76% inhibition at 10 μM. Compounds 5c and 5d showed strong BACE-1 inhibition at the submicromolar level with IC 50 = 0.38 and 0.44 μM, respectively, which almost doubled the activity of curcumin. They also showed single-digit micromolar inhibitory activity against MAO-B with IC 50 = 5.15 and 2.42 μM, respectively. They also had antioxidant activities and showed satisfactory metal-chelating properties toward Fe +2 , Zn +2 , and Cu +2 , inhibiting oxidative stress in AD brains. Furthermore, compounds 5c and 5d showed acceptable relative safety upon normal cells SH-SY5Y and HepG2. It was shown that 5c and 5d were blood−brain barrier (BBB) penetrants by online prediction. Taken together, these multifunctional properties highlight that compounds 5c and 5d can serve as promising candidates for the further development of multifunctional drugs against AD.

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Aducanumab: A new hope in Alzheimer's disease

Cited by 12 publications

References 100 publications

Monoclonal antibodies treatment for Alzheimer’s dementia – a literature review

Monoclonal antibodies treatment for Alzheimer’s dementia – a literature review

A new era in Alzheimer’s disease management: exploring aducanumab’s potential

Modified Tacrine Derivatives as Multitarget-Directed Ligands for the Treatment of Alzheimer’s Disease: Synthesis, Biological Evaluation, and Molecular Modeling Study

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