NU 2019-095
INVENTORS
Grant Barish*
Meredith Sommars
Madhavi Senagolage
SHORT DESCRIPTION
Targeting B cell lymphoma protein 6 (BCL6) with small molecule inhibitors as a therapeutic strategy for non-alcoholic fatty liver disease.
BACKGROUND
Obesity is widely prevalent and linked to multiple comorbidities including metabolic dysfunction-associated fatty liver disease (previously known as non-alcoholic fatty liver disease) or MAFLD. Fatty liver disease is predicted to become the leading cause of end-stage liver disease in the next decade. Currently, there is only one approved therapeutic for MAFLD which targets the transcriptional network controlled by thyroid receptor beta in liver. BCL6 is a transcriptional repressor that plays a critical role in B cell development and lymphogenesis, though it is broadly expressed in non-immune tissues, including the liver and adipose tissue where its function is under active investigation.
ABSTRACT
Northwestern researchers have demonstrated that BCL6 represses a liver gene network involved in lipid breakdown, which contributes to non-alcoholic fatty liver disease. Genetic ablation of BCL6 in hepatocytes prevented the development of fatty liver and improved glucose homeostasis in mice. Inhibiting BCL6 function using small molecule drugs is a promising therapeutic strategy that could address the unmet medical needs for MAFLD.
APPLICATIONS
Treatment strategy for fatty liver disease
Potential treatment strategy for pre-diabetes and diabetes
Potential treatment for obesity
ADVANTAGES
Reduces intrahepatic fat
Reduces hepatic insulin resistance
PUBLICATIONS Sommars M. et. al. (2019). Dynamic repression by BCL6 controls the genome-wide liver response to fasting and steatosis. Elife. 8: e43922.
IP STATUS
Issued U.S Patent No. 11,439,635
BCL6 represses peroxisome proliferator-activated receptor (PPAR) target genes to suppress fasting transcription and fatty acid oxidation. Deletion of BCL6 in hepatocytes enhances the burning of fat in the liver to protect from steatosis (fatty liver).