First Administration of the Fc-Attenuated Anti-β Amyloid Antibody GSK933776 to Patients with Mild Alzheimer’s Disease: A Randomized, Placebo-Controlled Study

Andreasen, Niels; Simeoni, Monica; Östlund, Henrik; Lisjö, Pia; Fladby, Tormod; Loercher, Amy; Byrne, Gerard; Murray, Frances; Scott‐Stevens, Paul; Wallin, Anders; Zhang, Yinghua Y.; Bronge, Lena; Zetterberg, Henrik; Nordberg, Agneta; Yeo, Astrid; Khan, Shahid A.; Hilpert, Jan; Mistry, Prafull

doi:10.1371/journal.pone.0098153

Cited by 28 publications

(22 citation statements)

References 22 publications

(35 reference statements)

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“…Other monoclonal anti-Abeta antibodies undergoing clinical testing had also been evaluated for safety. For instance, anti-Aβ mAb GSK933776 administered intravenously at doses of 1-6 mg increased total amyloid and Abeta42 levels in plasma and cerebrospinal fluid (CSF) (5). GSK933776 exhibited a favorable safety profile in the Phase I trial with no brain edema or hemorrhage in the 18 patients tested.…”

Section: Alzheimer's Disease: Variable Results From Clinical Trials Amentioning

confidence: 99%

Recent Developments in Understanding Brain Aging: Implications for Alzheimer’s Disease and Vascular Cognitive Impairment

Deák

Freeman

Ungvári

et al. 2015

GERONA

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As the population of the Western world is aging, there is increasing awareness of age-related impairments in cognitive function and a rising interest in finding novel approaches to preserve cerebral health. A special collection of articles in The Journals of Gerontology: Biological Sciences and Medical Sciences brings together information of different aspects of brain aging, from latest developments in the field of neurodegenerative disorders to cerebral microvascular mechanisms of cognitive decline. It is emphasized that although the cellular changes that occur within aging neurons have been widely studied, more research is required as new signaling pathways are discovered that can potentially protect cells. New avenues for research targeting cellular senescence, epigenetics, and endocrine mechanisms of brain aging are also discussed. Based on the current literature it is clear that understanding brain aging and reducing risk for neurological disease with age requires searching for mechanisms and treatment options beyond the age-related changes in neuronal function. Thus, comprehensive approaches need to be developed that address the multiple, interrelated mechanisms of brain aging. Attention is brought to the importance of maintenance of cerebromicrovascular health, restoring neuroendocrine balance, and the pressing need for funding more innovative research into the interactions of neuronal, neuroendocrine, inflammatory and microvascular mechanisms of cognitive impairment, and Alzheimer's disease.

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Section: Alzheimer's Disease: Variable Results From Clinical Trials Amentioning

confidence: 99%

Recent Developments in Understanding Brain Aging: Implications for Alzheimer’s Disease and Vascular Cognitive Impairment

Deák

Freeman

Ungvári

et al. 2015

GERONA

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“…29,56,58 GSK933776, which recognizes the N-terminal region of Aβ and binds all forms of Aβ, raised CSF Aβ; testing in AD was stopped. 56,57,59 In AD, solanezumab, whose epitope is the middle region of Aβ and which binds monomers more than oligomers or plaques, increased CSF Aβ but did not affect the rate of decline in cognition, though it did appear to slow the decline in cognition in the subset of AD patients who had mild AD. 21,29,56,57,60 However, a subsequent trial in prodromal AD showed no effect on cognitive decline.…”

Section: Vaccination For Admentioning

confidence: 99%

Rationale for the development of an Alzheimer’s disease vaccine

Kwan

Konno

Chan

et al. 2019

Human Vaccines & Immunotherapeutics

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Vaccination traditionally has targeted infectious agents and thus has not heretofore been used to prevent neurodegenerative illness. However, amyloid β (Aβ) or tau, which can act like infectious proteins, or prions, might induce Alzheimer's disease (AD). Furthermore, evidence suggests that traditional infectious agents, including certain viruses and bacteria, may trigger AD. It is therefore worth exploring whether removing such targets could prevent AD. Although failing to treat AD patients who already display cognitive impairment, Aβ monoclonal antibodies are being tested in pre-symptomatic, at-risk individuals to prevent dementia. These antibodies might become the first AD therapeutics. However, their high cost will keep them out of the arms of the vast majority of patients, who increasingly live in developing countries. Because vaccines produce antibodies internally at much lower cost, vaccination might be the most promising approach to reducing the global burden of dementia.

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“…GSK933776 showed pharmacological activity and engaged target in plasma and CSF without causing brain amyloid-related imaging abnormalities-edema (ARIA-E/H) in patients with mild AD or MCI. 115,116 MABT5102A was a humanized Ab1-15 monoclonal antibody with IgG4 isotype. It can inhibit Ab aggregation and promote its disaggregation without vasogenic edema and cerebral microhemorrhage induced by overactivation of microglial cells.…”

Section: Amyloid-targeted Therapiesmentioning

confidence: 99%