Reversal of Cushing syndrome by antibody-mediated neutralization of ACBP/DBI
Authors:Zhe Shen1,2,3,a, Hui Pan1,2,4,a, Xiaolian Deng1,2,3, Oliver Kepp1,2, Isabelle Martins1,*, and Guido Kroemer1,2,5,*
1 Université Paris Cité, Centre de Recherche des Cordeliers, Equipe labellisée par la Ligue contre le cancer, Inserm U1138, Sorbonne Université, Paris, France. 2 Université Paris Saclay, Metabolomics and Cell Biology Platforms, UMS AMMICa, Gustave Roussy Institut, Villejuif, France. 3 Faculté de Médecine, Université Paris-Saclay, Le Kremlin Bicêtre, Paris, France. 4 Department of Hematology/Institute of Hematology, West China Hospital, Sichuan University, Chengdu, China. 5 Institut du Cancer Paris CARPEM, Department of Biology, Hôpital Européen Georges Pompidou, AP-HP, Paris, France.
a Equally contributed.
Keywords:
endozepin, hypercortisolism, neuroendocrine, obesity
Corresponding Author(s):
Conflict of interest statement:
HP, IM and GK are the inventors of patents covering the therapeutic utility of ACBP/DBI neutralization. OK is a scientific co-founder of Samsara Therapeutics. IM is a consultant for Osasuna Therapeutics. GK has been holding research contracts with Daiichi Sankyo, Eleor, Kaleido, Lytix Pharma, PharmaMar, Osasuna Therapeutics, Samsara Therapeutics, Sanofi, Sutro, Tollys, and Vascage. GK is on the Board of Directors of the Bristol Myers Squibb Foundation France. GK is a scientific co-founder of everImmune, Osasuna Therapeutics, Samsara Therapeutics and Therafast Bio. GK is in the scientific advisory boards of Hevolution, Institut Servier, and Rejuveron Life Sciences/Centenara Labs AG. GK is the inventor of patents covering therapeutic targeting of aging, cancer, cystic fibrosis and metabolic disorders. Among these patents, one "Methods for weight reduction" (US11905330B1) is relevant to this study. GK’s brother, Romano Kroemer, was an employee of Sanofi and now consults for Boehringer-Ingelheim. GK's wife, Laurence Zitvogel, has held research contracts with Glaxo Smyth Kline, Incyte, Lytix, Kaleido, Innovate Pharma, Daiichi Sankyo, Pilege, Merus, Transgene, 9 m, Tusk and Roche, was on the on the Board of Directors of Transgene, is a cofounder of everImmune, and holds patents covering the treatment of cancer and the therapeutic manipulation of the microbiota. The funders had no role in the design of the study, in the writing of the manuscript, or in the decision to publish the results.
Please cite this article as:
Zhe Shen, Hui Pan, Xiaolian Deng, Oliver Kepp, Isabelle Martins, Guido Kroemer (2026). Reversal of Cushing syndrome by antibody-mediated neutralization of ACBP/DBI. Cell Stress 10: 1-8. doi: 10.15698/cst2026.01.314
© 2026 Shen et al. This is an open-access article released under the terms of the Creative Commons Attribution (CC BY) license, which allows the unrestricted use, distribution, and reproduction in any medium, provided the original author and source are acknowledged.
Abstract:
Cushing syndrome (CS) is caused by an increase in endogenous or exogenous glucocorticoids, leading to major alterations in body composition, including visceral obesity, sarcopenia, osteoporosis, type 2 diabetes, and dyslipidemia. Cardiovascular complications resulting from CS are often lethal. We previously demonstrated that CS induced by oral corticosterone (CORT) supplementation in mice can be prevented by inhibition of the peptide hormone acyl-CoA binding protein (ACBP), encoded by the gene diazepam binding inhibitor (DBI). Here, we investigated whether ACBP/DBI inhibition could be used to treat, rather than prevent, CS. To this end, we initiated treatment with anti-ACBP/DBI monoclonal antibodies (mAbs) in mice three weeks after the start of CORT supplementation, when hyperphagia and body weight gain were already established. Two anti-ACBP/DBI mAbs, 7G4a (specific for mouse ACBP/DBI only) and 82 (which recognizes both mouse and human ACBP/DBI), were able to normalize food intake and halt weight gain in mice under continuous CORT treatment. In addition, both mAbs attenuated CORT-induced sarcopenia, adiposity in inguinal, perigonadal, and visceral fat depots, and fully restored metabolic parameters, including insulinemia, free fatty acids, triglycerides, and liver transaminases. In conclusion, neutralization of ACBP/DBI may serve as an effective therapeutic strategy for the treatment of established CS.