Therapeutic for reducing plasma triglyceride levels in patients with metabolic syndrome

This technology is a therapeutic method to reduce plasma triglycerides commonly elevated in obesity-induced metabolic syndrome.

Unmet Need: Improved therapeutic strategy for reducing plasma triglyceride levels

Obesity can result in a serious condition called metabolic syndrome. A core component of the syndrome is hypertriglyceridemia, or excess plasma triglycerides, which is a risk factor for coronary heart disease. Current therapies for hypertriglyceridemia include fibrate, omega-3 fatty acids, bile acid sequestrants, niacin, and statins. These treatments lower triglyceride levels insufficiently and the persistence of high triglyceride levels leaves patients at risk of a heart attack. Thus, there is an ongoing need to develop additional strategies that efficiently decrease triglyceride levels in alternative and complementary ways to current approaches.

The Technology: Effective reduction in plasma triglycerides and ApoC3 via gamma-secretase inhibition

This technology is a method for efficiently reducing the levels of plasma triglycerides and serum apolipoprotein C3 (ApoC3) by inhibiting the gamma-secretase complex. Gamma-secretase inhibition lowers plasma triglyceride-rich lipoproteins by stabilizing the low-density lipoprotein receptor. As such, small molecule or oligonucleotide gamma-secretase inhibitors could be used as potential treatment options for targeting gamma-secretase in patients, leading to improved glucose metabolism. This therapeutic strategy provides an effective method for patients with metabolic disorders such as diabetes, obesity, and hypertriglyceridemia to reduce their plasma triglyceride levels.

This technology has been validated in mouse models.

Applications:

• Management of plasma triglycerides levels
• Lowering of coronary heart disease and pancreatitis risks
• Management of metabolic syndrome and fatty liver disease
• Improvement of insulin resistance and lowering of blood sugar
• Treatment of hypertriglyceridemia-related conditions (e.g. xanthomas, atherosclerosis)

Advantages:

• Effective in lowering triglycerides beyond current methods
• Complementary to current treatments for metabolic syndrome
• Versatile treatment that allows individual or multi-hit inhibition of gamma-secretase components
• Targeted treatment when selecting liver-specific gamma-secretase inhibition

Lead Inventor:

Utpal Pajvani, M.D., Ph.D.

Patent Information:

Patent Status

Related Publications:

• Kim K, Goldberg IJ, Graham MJ, Sundaram M, Bertaggia E, Lee SX, Qiang L, Haeusler RA, Metzger D, Chambon P, Yao Z, Ginsberg HN, Pajvani UB. “γ-secretase inhibition lowers plasma triglyceride-rich lipoproteins by stabilizing the LDL receptor” Cell Metab. 2018 Apr 3; 27(4): 816-827.30121-9)

• Sparling DP, Yu J, Kim K, Zhu C, Brachs S, Birkenfeld AL, Pajvani UB. ”Adipocyte-specific blockade of gamma-secretase, but not inhibition of Notch activity, reduces adipose insulin sensitivity” Mol Metab. 2015 Dec 2; 5(2): 113-121.

Tech Ventures Reference:

• IR CU14176

• Licensing Contact: Cynthia Lang