By 2020, nonalcoholic steatohepatitis (NASH), a type of nonalcoholic fatty liver disease, is expected to become the leading cause of liver transplants in the United States.

“There is currently no cure for NASH or FDA-approved treatment, so we are developing drug strategies with unique modes of action,” said Webster Santos, professor of chemistry and the Cliff and Agnes Lilly Faculty Fellow of Drug Discovery in the College of Science at Virginia Tech.

Santos has developed novel mitochondrial uncouplers, which work to increase metabolism and decrease fat accumulation. Therapeutic applications for these technologies include obesity, NASH, and liver fibrosis.

Virginia Tech’s Link, License, Launch has recently facilitated a partnership between Santos and the biotech company Continuum Biosciences, a subsidiary of Life Biosciences to license and help deliver these drugs to market.

Life Biosciences is the first and largest biotech company addressing the eight pathways of age-related decline (ARD) in totality. The company seeks to increase healthspans for everyone, including companion animals, by addressing the systemic breakdown of the body, rather than as a series of isolated symptoms and conditions. Life Biosciences has established daughter companies around the world, led by a respected scientists, to independently and collaboratively attack these pathways through pioneering research and product development.

In 2019, Link, License, Launch, which functions as a one-stop shop for companies and those interested in starting new ventures, made strategic hires in Blacksburg, Roanoke, and Northern Virginia and began operations as an integrated team along the complete continuum from discovery to market, according to Associate Vice President for Innovation and Partnerships Brandy Salmon.

“Link, License, Launch serve as the front door for inventors and partners, working in collaboration with Virginia Tech Intellectual Properties. Our model is simple: engage early and often with our industry partners to understand their changing strategic needs. We match those needs to Virginia Tech’s extensive network of assets and strengths to ensure partnerships today create impact tomorrow,” said Jason Piché, president of Virginia Tech Intellectual Properties and director of License: Center for Technology Commercialization.

Virginia Tech Intellectual Properties and License patented Santos’ discovery and facilitated the licensing agreement with Continuum Biosciences. “This enables a certain amount of protection and value for the early development of this technology," said Piché.

License and Launch commercialize technologies and support new Virginia Tech start-ups to provide a path to market in the biomedical, pharmaceutical, engineering, and agricultural arenas. 

“Great discoveries like those made by Dr. Santos and his colleagues deserve a chance to reach markets where they can improve the lives of patients. We are passionate about supporting the Virginia Tech community to expand the reach and impact of research through commercialization and start-ups. This deal is a great example of the global good made possible through Virginia Tech,” said Salmon.

The partnership with Continuum will help take Santos’ mitochondrial uncouplers from bench to bedside to treat nonalcoholic steatohepatitis (NASH), a type of nonalcoholic fatty liver disease and liver fibrosis.

NASH is a condition characterized by fat accumulation in the liver that results in chronic inflammation that can progress to cirrhosis of the liver and, ultimately, liver cancer. According to the National Institutes of Health, there are 26 million patients with NASH in the United States, and approximately 30 to 40 percent of patients with NASH-derived cirrhosis will experience a liver-related death.

The compounds that Santos developed to treat NASH are known as mitochondrial uncouplers. Mitochondria are organelles that are responsible for energy production and can be found in large numbers in most cells.

Mitochondrial uncouplers are molecules that shuttle protons across the mitochondrial membrane to increase metabolism and decrease fat accumulation. These molecules also lower reactive oxygen species production in the mitochondria, which contributes to liver fibrosis in NASH.

So far, Santos and his collaborators have developed novel uncouplers that can be given orally. The researchers have tested this molecule in animal trials and have shown that the compound minimizes fat accumulation, mitochondrial dysfunction, and liver inflammation.

“It is shown to be safe over a broad therapeutic concentration range because it lacks off-target activity and it is self-limiting, meaning that it will stop working once a therapeutic level is reached,” said Santos, who is also an affiliated faculty member of the Fralin Life Sciences Institute and member of VT Center for Drug Discovery.

The next steps for Santos and Continuum Biosciences will be to conduct more toxicology studies and apply for human trials through the FDA. These newly identified and safe mitochondrial uncouplers are expected to improve patient outcomes and reduce health care costs by reducing the number of liver transplants and reducing instances of liver cancer and end-stage liver disease. They may also be used to treat obesity, systemic hypertension, insulin resistance, type II diabetes, and other conditions that are commonly associated with NASH.

Santos is a co-founder of three biotech companies and received the Schug Research Award as well as an Innovator’s award at Virginia Tech. He is on the editorial advisory board of current topics in medicinal chemistry, medicinal research reviews, as well as Boron in the Americas. His current research centers on developing drugs for fatty liver disease, cancer, and multiple sclerosis, as well as synthetic methodology of installing boron and silicon onto carbon bonds and chemical biology of targeting HIV-1 RNAs.

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