Safety and pharmacokinetics of PF-04360365 following a single-dose intravenous infusion in Japanese subjects with mild-to-moderate Alzheimerâs disease: a multicenter, randomized, double-blind, placebo-controlled, dose-escalation study

Miyoshi, Izuru; Fujimoto, Yoko; Yamada, Masahito; Abe, Sadahiro; Zhao, Qinying; Cronenberger, Carol; Togo, Kanae; Ishibashi, Tomoko; Bednar, Martin M.; Kupiec, James W.; Binneman, Brendon

doi:10.5414/cp201816

Cited by 26 publications

(20 citation statements)

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“…It diminishes the amyloid burden through an outflow of Aβ from the hippocampus induced by the reduction of the peptide in plasma 77 . Results of the clinical trials evidenced no significant improvement in cognitive impairment of patients with mild to moderate AD 78,79 and at the moment is being tested for the treatment of cerebral amyloid angiopathy (CAA) (https://clinicaltrials.gov; Identifier: NCT01821118).…”

Section: Drugmentioning

confidence: 99%

Amyloid-beta immunotherapy: the hope for Alzheimer disease?

Barrera-Ocampo

Lopera

2016

Colomb Med

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Alzheimer disease (AD) is the most prevalent form of dementia of adult-onset, characterized by progressive impairment in cognition and memory. There is no cure for the disease and the current treatments are only symptomatic. Drug discovery is an expensive and time-consuming process; in the last decade no new drugs have been found for AD despite the efforts of the scientific community and pharmaceutical companies. The Aβ immunotherapy is one of the most promising approaches to modify the course of AD. This therapeutic strategy uses synthetic peptides or monoclonal antibodies (mAb) to decrease the Aβ load in the brain and slow the progression of the disease. Therefore, this article will discuss the main aspects of AD neuropathogenesis, the classical pharmacologic treatment, as well as the active and passive immunization describing drug prototypes evaluated in different clinical trials.

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Section: Drugmentioning

confidence: 99%

Amyloid-beta immunotherapy: the hope for Alzheimer disease?

Barrera-Ocampo

Lopera

2016

Colomb Med

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“…Ponezumab is a humanized IgG2 mAb that binds to the C-terminal region of Aβ (Aβ33-40). Although Phase 1 studies of ponezumab showed sufficient safety [64,65], its Phase 2 trials revealed no significant cognitive improvement in patients with mild to moderate AD [66]. The development of ponezumab for AD was discontinued, although it is still in Phase 2 trials for cerebral amyloid angiopathy (CAA).…”

Section: Immunotherapies Targeting Aβmentioning

confidence: 99%

Present and Future Therapies for Alzheimer’s Disease

Nagase¹,

Nakayama²

2018

Immunoregulatory Aspects of Immunotherapy

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Alzheimer's disease (AD) is an incurable, progressive neurodegenerative disorder and the most common type of dementia. Although four kinds of drugs are currently available for AD, these are symptomatic treatments and do not halt disease progression. Therefore, there is an urgent need for development of curative drugs for AD. Amyloid plaques are the main disease hallmark observed in AD brains. As amyloid-β (Aβ) is a major constituent of amyloid plaques, Aβ has been supposed to be pathogenic for AD (amyloid hypothesis). Thus, current, mainstream AD drug development is based around this hypothesis. In particular, both active and passive immunotherapies are aggressively employed. However, most clinical trials based on this hypothesis, including immunotherapies, failed to improve cognitive impairment in AD. Therefore, it is likely that AD onset is caused by factors besides Aβ. We have previously demonstrated that the intracellular domain of amyloid precursor protein (AICD) induces dynamic changes in gene expression and neuron-specific apoptosis, probably related to AD pathogenesis. Therefore, AICD may be a favorable target for AD therapies. In this chapter, current trials for AD therapies, especially immunotherapies targeting Aβ, are summarized. In addition, therapies targeting tau, another possible pathogenic molecule, are also described. Furthermore, we discuss the possibility of AICD as a novel therapeutic target for AD.

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“…113 And another clinical trial also showed similar results. 114 GSK-933776 is a humanized Fc-attenuated/inactivated anti-Ab monoclonal antibody. 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.…”

Section: Amyloid-targeted Therapiesmentioning

confidence: 99%