ALD1613, a Novel Long-Acting Monoclonal Antibody to Control ACTH-Driven Pharmacology.

Autor:	Feldhaus AL; Alder BioPharmaceuticals, Inc., Bothell, Washington 98011., Anderson K; Alder BioPharmaceuticals, Inc., Bothell, Washington 98011., Dutzar B; Alder BioPharmaceuticals, Inc., Bothell, Washington 98011., Ojala E; Alder BioPharmaceuticals, Inc., Bothell, Washington 98011., McNeill PD; Alder BioPharmaceuticals, Inc., Bothell, Washington 98011., Fan P; Alder BioPharmaceuticals, Inc., Bothell, Washington 98011., Mulligan J; Alder BioPharmaceuticals, Inc., Bothell, Washington 98011., Marzolf S; Alder BioPharmaceuticals, Inc., Bothell, Washington 98011., Karasek C; Alder BioPharmaceuticals, Inc., Bothell, Washington 98011., Scalley-Kim M; Alder BioPharmaceuticals, Inc., Bothell, Washington 98011., Stewart E; Alder BioPharmaceuticals, Inc., Bothell, Washington 98011., Billgren J; Alder BioPharmaceuticals, Inc., Bothell, Washington 98011., Rubin V; Alder BioPharmaceuticals, Inc., Bothell, Washington 98011., Schneider K; Alder BioPharmaceuticals, Inc., Bothell, Washington 98011., Jurchen D; Alder BioPharmaceuticals, Inc., Bothell, Washington 98011., Snow K; Alder BioPharmaceuticals, Inc., Bothell, Washington 98011., Barnett S; Alder BioPharmaceuticals, Inc., Bothell, Washington 98011., Bengtsson B; Alder BioPharmaceuticals, Inc., Bothell, Washington 98011., Baker B; Alder BioPharmaceuticals, Inc., Bothell, Washington 98011., Latham JA; Alder BioPharmaceuticals, Inc., Bothell, Washington 98011., Allison D; Alder BioPharmaceuticals, Inc., Bothell, Washington 98011., Garcia-Martinez LF; Alder BioPharmaceuticals, Inc., Bothell, Washington 98011.
Jazyk:	angličtina
Zdroj:	Endocrinology [Endocrinology] 2017 Jan 01; Vol. 158 (1), pp. 1-8.
DOI:	10.1210/en.2016-1455
Abstrakt:	Adrenocorticotropic hormone (ACTH) is the primary regulator of adrenal glucocorticoid production. Elevated levels of ACTH play a critical role in disease progression in several indications, including congenital adrenal hyperplasia and Cushing disease. We have generated a specific, high-affinity, neutralizing monoclonal antibody (ALD1613) to ACTH. In vitro, ALD1613 neutralizes ACTH-induced signaling via all 5 melanocortin receptors and inhibited ACTH-induced cyclic adenosine monophosphate accumulation in a mouse adrenal cell line (Y1). ALD1613 administration to wild-type rats significantly reduced plasma corticosterone levels in a dose-dependent manner. In rodent models with either chronic infusion of ACTH or acute restraint stress-induced ACTH, corticosterone levels were significantly reduced by ALD1613. Administration of ALD1613 to nonhuman primates on days 1 and 7 stably reduced plasma cortisol levels >50% for 57 days. ALD1613 demonstrates the potential of a monoclonal antibody to be an effective therapeutic for conditions with elevated ACTH levels. (Copyright © 2017 by the Endocrine Society.)
Databáze:	MEDLINE
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