In a novel research study, a team led by scientists at the Harvard T.H. Chan School of Public Health detailed the pre-clinical development of a promising therapeutic for metabolic conditions, including fatty liver disease and type 2 diabetes. The study is entitled “Development of a therapeutic monoclonal antibody that targets secreted fatty acid binding protein aP2 to treat type 2 diabetes,” and was published in the journal Science Translational Medicine.
Adipose tissue is an endocrine organ that secretes numerous cytokines, adipokines, and lipokines that regulate aspects of systemic metabolic homeostasis. Obesity-related alterations in the endocrine output of adipose tissue are linked to the development of a variety of metabolic disorders, including cardiovascular disease and type 2 diabetes.
In a previous study, researchers identified the protein aP2 (FABP4) as a hormone that mediates the communication between the liver and the adipose tissue. In humans with atherosclerosis, diabetes and obesity there is an increase in the levels of aP2. Mutations that decrease the levels of this protein have been found to reduce the risk for conditions such as heart disease, diabetes and dyslipidemia. In this context, approaches to change the function of aP2 may bring new avenues for therapeutic strategies to fight these chronic conditions.
The team developed new monoclonal antibodies targeting the protein aP2, and discovered that one of the tested antibodies improved the regulation of glucose in two mouse models of obesity. In addition, researchers also observed that the antibody induced a reduction in liver fat.
“The importance of this study is two-fold: first, demonstrating the importance of aP2 as a critical hormone in abnormal glucose metabolism, and secondly, showing that aP2 can be effectively targeted to treat diabetes and potentially other immunometabolic diseases,” said the study’s senior author, Dr. Gökhan S. Hotamisligil, J.S. Simmons Professor of Genetics and Metabolism and chair of the Department of Genetics and Complex Diseases and the Sabri Ülker Center at Harvard Chan School, in a news release.
According to the authors, these monoclonal antibodies may be transformative first-in-class therapeutics against immunometabolic and obesity-related metabolic disorders. This strategy is, however, still at a preclinical stage and will require extensive efficacy and safety assessment before it can be considered an option for humans.