Gene silencing for the treatment of metabolic dysfunction-associated steatohepatitis (MASH)

Unmet Need: Identification of drug targets for the treatment of MASH

Nonalcoholic fatty liver disease is the most common chronic liver disease worldwide and encompasses a histological spectrum, ranging from simple steatosis to metabolic dysfunction-associated steatohepatitis (MASH). Although many individuals with steatosis do not develop more severe disease, progression to MASH can result in both cirrhosis and end-stage liver disease. Unfortunately, there are limited treatment options for MASH, largely due to a poor understanding of MASH pathology. More specifically, there is a limited understanding of the conversion of steatosis to MASH. Thus, there is a need for the identification of potential molecular targets to block the progression of steatosis to MASH.

The Technology: Silencing caspase 8-meteorin pathway to treat MASH

This technology identifies the silencing of the caspase 8 (CASP8)-meteorin (METRN) pathway as a therapeutic strategy for the treatment of metabolic dysfunction-associated steatohepatitis (MASH). The caspase 8 protein was demonstrated to play a critical role in MASH pathogenesis; in mouse models, knockout of the CASP8 gene in hepatocytes blocked the progression of steatosis to MASH. Further, it was shown that caspase 8 promotes MASH by inducing the expression of METRN, which encodes meteorin. METRN has never been implicated in any liver function or disease but is expressed highly in fibrotic liver tissue. Therefore, this technology uses hepatocyte-specific silencing of CASP8 or METRN to block the progression of fibrotic MASH.

Applications:

Treatment for MASH
Prevention of steatosis conversion to MASH
Biomarker development for detection of CASP8 and METRN
Research tool for measuring plasma CASP8 and METRN gene products
Early diagnostic tool for MASH using METRN as a biomarker
Research tool to understand the mechanism of caspase 8-meteorin pathway

Advantages:

Directly prevents the conversion of steatosis to MASH
Non-invasive treatment option
Evidence-based genetic drug target

Lead Inventor:

Ira Tabas, MD, Ph.D.

Patent Information:

Patent Pending(WO/2024/191962)

Related Publications:

Tech Ventures Reference:

IR CU23021
Licensing Contact: Joan Martinez