Comparison of Pharmacokinetics, Pharmacodynamics, Safety, and Tolerability of the Amyloid β Monoclonal Antibody Solanezumab in Japanese and White Patients With Mild to Moderate Alzheimer Disease

Uenaka, Kazunori; Nakano, Masako; Willis, Brian A.; Friedrich, Stuart; Ferguson-Sells, Lisa; Dean, Robert A.; Ieiri, Ichiro; Siemers, Eric

doi:10.1097/wnf.0b013e31823a13d3

Cited by 38 publications

(19 citation statements)

References 6 publications

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“…40 Solanezumab, an immune drug that also removes Aβ from the AD brain into blood, 41 has been shown to delay cognitive decline in those who have an early stage of AD. 42 Induced removal of Aβ from the brain into the blood by the amylin class peptides also could be used in a challenge test to specifically reflect and diagnose AD pathology in the brain.…”

Section: Discussionmentioning

confidence: 99%

Intraperitoneal injection of the pancreatic peptide amylin potently reduces behavioral impairment and brain amyloid pathology in murine models of Alzheimer’s disease

et al. 2014

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Amylin, a pancreatic peptide, and amyloid-beta peptides (Aβ), a major component of Alzheimer's disease (AD) brain, share similar β-sheet secondary structures, but it is not known whether pancreatic amylin affects amyloid pathogenesis in the AD brain. Using AD mouse models, we investigated the effects of amylin and its clinical analog, pramlintide, on AD pathogenesis. Surprisingly, chronic intraperitoneal (i.p.) injection of AD animals with either amylin or pramlintide reduces the amyloid burden as well as lowers the concentrations of Aβ in the brain. These treatments significantly improve their learning and memory assessed by two behavioral tests, Y maze and Morris water maze. Both amylin and pramlintide treatments increase the concentrations of Aβ1-42 in cerebral spinal fluid (CSF). A single i.p. injection of either peptide also induces a surge of Aβ in the serum, the magnitude of which is proportionate to the amount of Aβ in brain tissue. One intracerebroventricular injection of amylin induces a more significant surge in serum Aβ than one i.p. injection of the peptide. In 330 human plasma samples, a positive association between amylin and Aβ1-42 as well as Aβ1-40 is found only in patients with AD or amnestic mild cognitive impairment. As amylin readily crosses the blood–brain barrier, our study demonstrates that peripheral amylin's action on the central nervous system results in translocation of Aβ from the brain into the CSF and blood that could be an explanation for a positive relationship between amylin and Aβ in blood. As naturally occurring amylin may play a role in regulating Aβ in brain, amylin class peptides may provide a new avenue for both treatment and diagnosis of AD.

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Section: Discussionmentioning

confidence: 99%

Intraperitoneal injection of the pancreatic peptide amylin potently reduces behavioral impairment and brain amyloid pathology in murine models of Alzheimer’s disease

et al. 2014

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“…These GSM have also shown a decrease of plasma Aβ [74-76] but the results regarding any Aβ-rebound are contradictory for GSMs [75,76]. On the other hand, passive immunotherapy results from clinical trials suggest that there is a dose-dependent transient increase of plasma Aβ in response to the monoclonal anti-Aβ antibody infusion and this was reported to last several weeks [77]. Thus, more research is clearly needed to elucidate the effects of these disease-modifying therapies on plasma Aβ levels.…”

Section: Association Of Aβ With Ad and Cerebrovascular Diseasementioning

confidence: 99%

Plasma amyloid beta measurements - a desired but elusive Alzheimer's disease biomarker

Toledo

Shaw

Trojanowski

2013

Alzheimers Res Ther

116

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Cerebrospinal fluid and positron emission tomography biomarkers accurately predict an underlying Alzheimer's disease (AD) pathology; however, they represent either invasive or expensive diagnostic tools. Therefore, a blood-based biomarker like plasma amyloid beta (Aβ) that could correlate with the underlying AD pathology and serve as a prognostic biomarker or an AD screening strategy is urgently needed as a cost-effective and non-invasive diagnostic tool. In this paper we review the demographic, biologic, genetic and technical aspects that affect plasma Aβ levels. Findings of cross-sectional and longitudinal studies of plasma Aβ, including autosomal dominant AD cases, sporadic AD cases, Down syndrome cases and population studies, are also discussed. Finally, we review the association between cerebrovascular disease and Aβ plasma levels and the responses observed in clinical trials. Based on our review of the current literature on plasma Aβ, we conclude that further clinical research and assay development are needed before measures of plasma Aβ can be interpreted so they can be applied as trait, risk or state biomarkers for AD.

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“…A growing body of information exists in the scientific literature regarding the pharmacokinetic (PK) and pharmacodynamic (PD) properties of biotherapeutic agents in the Chinese population, particularly in how they compare with non‐Chinese. While there are a number of publications characterizing the PK and PD of therapeutic monoclonal antibodies in Asian versus non‐Asian subjects, this report appears to be the first to compare serum exposures and the biologic effects of an endogenous cytokine between Chinese and non‐Chinese subjects.…”

mentioning

confidence: 99%

Interferon beta assessment in non-Chinese and Chinese subjects: Pharmacokinetics and pharmacodynamic activity of an endogenous cytokine are not race dependent

Rogge

Liu

Galluppi

2014

The Journal of Clinical Pharmacology

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Interferon beta-1a (IFNβ-1a) is a first-line therapy for relapsing multiple sclerosis when administered as 30 mcg intramuscularly (IM) once weekly. This endogenous cytokine displays pharmacokinetic (PK) attributes consistent with a glycoprotein of 20-kDa molecular weight that is administered IM. In this study, 24 healthy Chinese subjects (11 male, 13 female) each received 4 once-weekly 60-mcg IM doses of IFNβ-1a. Serial blood samples were drawn for PK and pharmacodynamic (PD) assessments following the first and last dose of drug. Results were compared with historical data from a recent PK/PD assessment conducted in non-Chinese subjects. Noncompartmental analysis revealed that no meaningful differences in either IFNβ-1a exposure or response were apparent between the Chinese and non-Chinese populations. Thus, it was concluded that no adjustment in dose regimen is warranted for future assessments of safety and efficacy in multiple sclerosis patients of Chinese origin.

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Comparison of Pharmacokinetics, Pharmacodynamics, Safety, and Tolerability of the Amyloid β Monoclonal Antibody Solanezumab in Japanese and White Patients With Mild to Moderate Alzheimer Disease

Cited by 38 publications

References 6 publications

Intraperitoneal injection of the pancreatic peptide amylin potently reduces behavioral impairment and brain amyloid pathology in murine models of Alzheimer’s disease

Intraperitoneal injection of the pancreatic peptide amylin potently reduces behavioral impairment and brain amyloid pathology in murine models of Alzheimer’s disease

Plasma amyloid beta measurements - a desired but elusive Alzheimer's disease biomarker

Interferon beta assessment in non-Chinese and Chinese subjects: Pharmacokinetics and pharmacodynamic activity of an endogenous cytokine are not race dependent

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