Chronic administration of an aglycosylated murine antibody of ponezumab does not worsen microhemorrhages in aged Tg2576 mice.
Curr Alzheimer Res
; 9(9): 1059-68, 2012 Nov.
Article
em En
| MEDLINE
| ID: mdl-22631613
ABSTRACT
Cerebral vasogenic edema and microhemorrhages are potential safety concerns for compounds intended to treat subjects with Alzheimer's disease (AD) by targeting amyloid ß (Aß). Ponezumab (PF-04360365) is an investigational anti-Aß monoclonal antibody. Two hundred female mice (APP(K670N;M671L); Tg2576) 16-19 months old received an aglycosylated CHO-derived murine surrogate of ponezumab by intraperitoneal administration once weekly for up to 26 weeks at doses of 0, 10, 30, or 100 mg/kg. Drug exposure and plasma Aß levels increased with increasing dose. After 26 weeks, the 100 mg/kg group had significantly greater plasma levels of Aß(1-x) and Aß(x-40) than the vehicle group (p < 0.001). Brain microhemorrhages were identified histologically using hematoxylin and eosin and/or Perls' Prussian blue iron staining. The incidence in the vehicle group was equal to or higher than those of the treated groups. There was no evidence of vasogenic edema. In summary, intraperitoneal administration of a murine surrogate of ponezumab to aged Tg2576 mice for up to 6 months did not produce any compound-related brain microhemorrhage or other pathologies.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Edema Encefálico
/
Hemorragia Cerebral
/
Doença de Alzheimer
/
Anticorpos Monoclonais Humanizados
Limite:
Animals
Idioma:
En
Revista:
Curr Alzheimer Res
Assunto da revista:
NEUROLOGIA
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Estados Unidos