Ohio State Pharmacy Researchers Awarded NIH Grant to Explore New Treatment for Liver Cancer

Laura Wise-Blau
Thomas SchmittgenThomas Schmittgen, PhD

Columbus, Ohio— Two Ohio State University College of Pharmacy faculty will share a $3.2 million grant from the National Institutes of Health to study treatment options for the type of liver cancer known as hepatocellular carcinoma, the third most prevalent cancer in the world. Thomas Schmittgen, PhD, associate professor and chair, and Mitch Phelps, PhD, assistant professor, both in the division of pharmaceutics and pharmaceutical chemistry, will study therapeutic RNAs for the treatment of hepatocellular carcinoma, or HCC. The five-year grant from the NIH's Extracellular RNA Communication Common Fund program is one of only 24 awarded nationwide in this initiative.

The Extracellular RNA research will rapidly advance understanding of exRNA. RNA, or ribonucleic acid, is a key regulator of gene activity. Previously thought to reside only within cells, researchers now know that RNA can be exported, serving as an important link in cell-to-cell communication. Investigations funded from this initiative will center on these external, or exRNAs, including potential for using exRNAs as therapeutic molecules.

The research team led by Schmittgen and Phelps will focus on using exRNA to develop a novel type of cancer treatment based on a new class of biomolecules called microRNA, which serve as a very specific control point for how a gene operates.

According to Schmittgen, certain microRNAs normally function to suppress tumor growth. Yet in some cancers, including HCC, their absence contributes to the development of tumors. The grant will allow Schmittgen and Phelps to experiment with treating HCC by replenishing microRNA-199, a specific microRNA that is often decreased in HCC tumors, in the liver.

Mitch PhelpsMitch Phelps, PhD

Currently, RNA’s instability in the body has impeded efforts to effectively use this molecule as a drug. Therefore, therapeutic RNAs require some type of drug delivery system in order to be effective.

The grant comprises two phases. In the first phase, Schmittgen and Phelps will load therapeutic microRNA-199 into microvesicles, naturally-occurring bodies that are shed from various cells. The design to synthesize and package  microRNA-199 into microvesicles was developed in Schmittgen’s laboratory in 2012.

“This delivery method has three important features: enhanced drug stability, targeting to the tumor and production of the RNA drug by the same cells that produce the microvesicles,” says Schmittgen. “Since therapeutic RNAs are costly to synthesize, it is our hope that natural production and packaging of the RNA into microvesicles may someday be affordable and mainstream.”

In the second phase, the researchers will investigate the ability of the microvesicles to find their target within the body. Notes Phelps: “As with all new therapies, we need to learn how these microvesicles will be distributed to various tissues and organs and how effectively they achieve their intended purpose, which in this case is to destroy HCC tumors in the liver.”

NIH Common Funds support high-impact programs aimed at freeing roadblocks to scientific discovery. The grants leverage emerging scientific opportunities across multiple biomedical fields, so that transformative human health advances can be made swiftly and effectively. 

HCC is the most common of liver cancers. According to the National Cancer Institute, some 31,640 new cases of HCC will be diagnosed in the U.S. this year. HCC is typically caused by scarring in the liver, known as cirrhosis. Cirrhosis can be developed through alcohol abuse, hepatitis B or C, chronic inflammation of the liver, iron overload, or autoimmune diseases of the liver. Prognosis for HCC is poor, with only a 10–20 percent survival rate.

The Ohio State team of investigators involved in the exRNA project includes Melissa Piper, Chenglong Li, Michael Paulaitis, Tracey Papenfuss and Xiaokui Mo.