A peptide therapeutic for atherosclerosis that restores lipid and cholesterol homeostasis


The currently most prescribed therapy for atherosclerosis is statins, which act on a single target to block synthesis of cholesterol. Instead of only one target, the Vanderbilt therapeutic (peptide cSN50) can "in a one swipe" suppress at least three targets for the current therapies, 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, a rate-controlling enzyme of the pathways producing cholesterol, Niemann-Pick C1-like 1 (NPC1L1) protein that captures extracellular cholesterol in the liver and gut, and proprotein convertase subtilisin/kexin type 9 (PCSK9) that accelerates LDL receptor turnover. cSN50 is a bi-functional nuclear transport modulator (NTM) that regulates transcription factors important in lipid and cholesterol homeostasis as well as inflammation. The striking in vivo result of cSN50 treatment administered to Western diet-fed mice was lower plasma and liver levels of cholesterol and triglycerides than in saline-treated control animals, with a concurrent improvement in liver function and normalized blood glucose and body weight. An obvious decrease in the development of atherosclerosis in arteries was also observed in cSN50-treated mice compared to controls. These studies indicate that NTM-based therapeutics could provide an ideal alternative to statins for extended treatment. Though not yet tested in humans or non-human primates, continuous treatment with cSN50 for up to 8-weeks has showed no toxicity in rodent models.

In the figure below, lipid accumulation (A and C) and markers of inflammation (D) are reduced in the livers of mice treated with cSN50 for 8 weeks, while increased cholesterol in their feces (B) demonstrates improved cholesterol clearance. As shown in (E), the atherosclerosis–suppressing effect of cSN50 is time-dependent, and a reduction in lesions even when treatment is begun 4 weeks after diet initiation indicates the potential for cSN50 to arrest development of atherosclerotic lesions: A) Liver concentrations of cholesterol and triglycerides, B) Fecal cholesterol, C) Liver sections stained with Oil-red-O for neutral lipids, D) Liver transaminases ALT and AST in plasma, E) Average atherosclerotic lesion area in different treatment groups determined by Oil-Red-O analysis of the aortic sinus.



• Reduces cholesterol and triglycerides while improving liver function in a murine model

• Atherosclerosis is lowered by 63% in a murine model

• Highly soluble and non-toxic

• Initial studies indicate a plasma half-life of 44 hours

• Engineered to cross the plasma membrane for rapid bio-distribution


Vanderbilt has both issued and pending patents for this technology. We are seeking either a licensing partner and/or a sponsored research agreement for further development. For additional information, please see this article: http://jaha.ahajournals.org/content/2/2/e000093

Jack HawigerAmy MajorJozef ZienkiewiczYan LiuRuth Ann VeachRobert Collins
Licensing manager: 
Janis Elsner

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