γ-secretase complex inhibitor nanoparticles for NASH

This technology is a nanoparticle that encapsulates γ-secretase complex inhibitors, which can be administered for treatment of NASH.

Unmet Need: Treatment options for NASH

The prevalence of nonalcoholic steatohepatitis (NASH) has been increasing in recent years, yet treatment options remain limited. The connection between type 2 diabetes mellitus and NASH has been extensively studied, with recent discoveries demonstrating that activation of the cell signaling pathway known as Notch leads to poorer outcomes for NASH. Therefore, inhibition of Notch is postulated as a method of NASH treatment. While inhibitors of Notch do improve NASH-related symptoms, the side effects of these inhibitors prevent their usage, suggesting that a targeted approach is necessary.

The Technology: Targeted delivery of Notch inhibitors by nanoparticles for NASH treatment

This technology utilizes nanoparticles for specific delivery of γ-secretase complex inhibitors (GSI), a type of Notch inhibitor that has been extensively studied. These nanoparticles allow for localized delivery of the GSI to the liver while sparing other tissues. As a result, the side effects that were previously seen with general administration of GSIs, such as intestinal metaplasia, are abrogated, while maintaining the benefits of the GSIs. When administered in an in vivo model, the nanoparticles are able to reverse NASH-induced liver fibrosis.

This technology has been validated in mice models.

Applications:

• Treatment for NASH
• Delivery of other drugs and compounds to the liver
• Live monitoring of drug delivery to the liver

Advantages:

• Selective and targeted delivery to the liver
• Reverses NASH-induced liver fibrosis
• No gastrointestinal or splenic toxicity

Lead Inventors:

Utpal Pajvani, M.D., Ph.D.
Li Qiang, Ph.D.

Patent Information:

Patent Status

Related Publications:

• Richter LR, Wan Q, Wen D, Zhang Y, Yu J, Kang JK, Zhu C, McKinnon EL, Gu Z, Qiang L, Pajvani UB. “Targeted Delivery of Notch Inhibitor Attenuates Obesity-Induced Glucose Intolerance and Liver Fibrosis” ACS Nano. 2020 Jun 23;14(6):6878-6886

• Kim K, Yu J, Kang JK, Morrow JP, Pajvani UB. “Liver-selective γ-secretase inhibition ameliorates diet-induced hepatic steatosis, dyslipidemia and atherosclerosis.” Biochem Biophys Res Commun. 2020 Jul 5;527(4):979-984.

• Zhu C, Kim K, Wang X, Bartolome A, Salomao M, Dongiovanni P, Meroni M, Graham MJ, Yates KP, Diehl AM, Schwabe RF, Tabas I, Valenti L, Lavine JE, Pajvani UB. “Hepatocyte Notch activation induces liver fibrosis in nonalcoholic steatohepatitis” Sci Transl Med. 2018 Nov 21;10(468):eaat0344.

Tech Ventures Reference:

• IR CU20227

• Licensing Contact: Cynthia Lang