Year: 2016
Type: article
Abstract: 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.
Source: Endocrinology
DOI: 10.1210/en.2016-1455
Authors: Andrew L. Feldhaus, Katie Anderson, Benjamin Dutzar, Ethan Ojala, Patricia Dianne McNeill, Pei Fan, Jenny Mulligan, Sam Marzolf, Charlie Karasek, Michelle Scalley-Kim, Erica Stewart, Jens Billgren, Vanessa Rubin, Kathleen Schneider, David Jurchen, Kathy Snow, Shaun Barnett, Barbara Bengtsson, Brian Baker, John A. Latham, Dan Allison, Leon F. Garcia-Martinez
Institution: Alder (United States)
Language: English
Subfield: Endocrinology, Diabetes and Metabolism
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2558818096