MBOAT7-targeted therapies for the personalized treatment of NASH fibrosis

This technology is a therapeutic approach targeting an MBOAT7 risk variant for treating non-alcoholic steatohepatitis (NASH).

Unmet Need: Precision medicine for the treatment of NASH fibrosis

Non-alcoholic steatohepatitis (NASH) is one of the leading causes of chronic liver disease, but there are currently no approved drugs to treat NASH or halt its progression into liver fibrosis, cirrhosis, and liver cancer. Existing therapies fail to effectively target the underlying genetic and molecular causes and instead focus on managing symptoms, resulting in suboptimal patient outcomes. Addressing these shortcomings is crucial for improving patient outcomes and managing NASH more effectively.

The Technology: MBOAT7-targeted therapies for the treatment of NASH fibrosis

This technology targets an MBOAT7 risk variant, rs641738, for personalized therapeutic intervention in non-alcoholic steatohepatitis (NASH). This genetic risk variant is associated with major forms of liver injury and disease and results in reduced expression and activity of MBOAT7, which can lead to the development of NASH through its role in negative regulation of the hepatocyte TAZ signaling pathway. This therapeutic approach identifies patients with the rs641738 variant and employs a TAZ siRNA or MBOAT7-mRNA nanoparticles to increase MBOAT7 expression and silence TAZ expression, reducing liver inflammation and fibrosis.

This technology has been validated in mice.

Applications:

• Therapeutic target for nonalcoholic steatohepatitis (NASH)
• Personalized medicine for patients with the rs641738 risk variant
• Research tool for investigating fibrotic NASH

Advantages:

• Directly targets the hepatic TAZ pathway, addressing root causes of NASH fibrosis
• Potentially extends to other metabolic disorders linked to MBOAT7 and the hepatic TAZ pathway
• Minimizes off-target effects compared to broader gene therapies or conventional drug treatments

Lead Inventor:

Ira Tabas, M.D., Ph.D.

Patent Information:

Patent Pending(WO/2023/150678)

Related Publications:

• Wang X, Sommerfeld MR, Jahn-Hofmann K, Cai B, Filliol A, Remotti HE, Schwabe RF, Kannt A, Tabas I. “A Therapeutic Silencing RNA Targeting Hepatocyte TAZ Prevents and Reverses Fibrosis in Nonalcoholic Steatohepatitis in Mice.” Hepatol Commun. 2019 Jul;3(9): pp. 1221-1234.

• Wang X, Moore MP, Shi H, Miyata Y, Donnelly SK, Radiloff DR, Tabas I. “Hepatocyte-targeted siTAZ therapy lowers liver fibrosis in NASH diet-fed chimeric mice with hepatocyte-humanized livers.” Mol Ther Methods Clin Dev. 2023 Nov. 23; 31: 101165.

Tech Ventures Reference:

• IR CU22159

• Licensing Contact: Joan Martinez