Hypothalamic-pituitary-adrenal (HPA) axis dysfunction contributes to numerous human diseases and disorders. We developed a high affinity, ~1 pM Kd, monoclonal antibody (CTRND05) targeting corticotropin-releasing factor (CRF). In mice, CTRND05 blocks stress-induced corticosterone increases, counteracts effects of chronic variable stress, and induces other phenotypes consistent with suppression of the HPA axis. CTRND05 induces skeletal muscle hypertrophy and increases in lean body mass, effects not previously reported with small-molecule HPA-targeting pharmacologic agents. Multi-organ transcriptomics demonstrates broad HPA axis target engagement and reveals novel HPA-responsive pathways such as the Apelin-Apelin receptor system. These studies demonstrate the therapeutic potential of CTRND05 as a suppressor of the HPA axis, and serve as an exemplar of a potentially broader approach to target neuropeptides with immunotherapies, as both pharmacologic tools and novel therapeutics.
Futch, Hunter S. and McFarland, Karen N. and Moore, Brenda D. and Kuhn, M. Zino and Giasson, Benoit I. and Ladd, Thomas B. and Scott, Karen A. and Shapiro, Melanie R. and Nosacka, Rachel L. and Goodwin, Marshall S. and Ran, Yong and Cruz, Pedro E. and Ryu, Daniel H. and Croft, Cara L. and Levites, Yona and Janus, Christopher and Chakrabarty, Paramita and Judge, Andrew R. and Brusko, Todd M. and de Kloet, Annette D. and Krause, Eric G. and Golde, Todd, An Anti-CRF Antibody Suppresses the HPA Axis and Reverses Stress-Induced Phenotypes (February 14, 2019). Available at SSRN: https://ssrn.com/abstract=3334424 or http://dx.doi.org/10.2139/ssrn.3334424
This version of the paper has not been formally peer reviewed.
Subscribe to this free journal for more curated articles on this topic
FOLLOWERS
20
PAPERS
9,210
Feedback
Feedback to SSRN
If you need immediate assistance, call 877-SSRNHelp (877 777 6435) in the United States, or +1 212 448 2500 outside of the United States, 8:30AM to 6:00PM U.S. Eastern, Monday - Friday.
Download This Paper