Scientists at the Fralin Biomedical Research Institute at VTC have started a new biotechnology company to apply one of nature’s courier systems to deliver a potentially life-saving medication.

The work, led by Robert Gourdie, director of the Fralin Biomedical Research Institute’s Center for Heart and Reparative Medicine Research, takes advantage of nanoscale bubbles called exosomes.

But instead of shuttling biomolecules and genetic material throughout the body, these exosomes derived from cow’s milk will deliver a promising new drug to help patients after a damaging cardiac event.

In a study published in August in the Journal of the American Heart Association, Gourdie and colleagues showed that the alphaCT11 molecule had cardioprotective effects in mice, preventing the spread of cell death in heart muscle tissue – even when administered 20 minutes after a heart attack.

A challenge for realizing the potential of this therapeutic compound is getting it to the stricken heart tissue intact.

“The drug appears to be very effective, but the next question we’re asking is what is the best way to guide this drug to target heart cells, while making it convenient for patients to ingest? That’s what my lab and Tiny Cargo are addressing,” Gourdie said.

Peptide drugs, such as alphaCT11, are tiny, fragile chains of amino acids that aren’t absorbed into the bloodstream if they don't break down quickly in the stomach and small intestine. As a result, these types of drugs are often administered to patients via injections to overcome stability and absorption limitations.

Tiny Cargo’s nanosized technology seeks to overcome these challenges by using exosomes as delivery envelopes that patients can take by mouth instead.

Gourdie, the Commonwealth Research Commercialization Fund Eminent Scholar in Heart Reparative Medicine Research and a professor of biomedical engineering and mechanics in Virginia Tech’s College of Engineering, recently licensed the intellectual property through Virginia Tech’s LICENSE: Center for Technology Commercialization. He formed The Tiny Cargo Co. in Roanoke, Virginia, to carry the idea to the clinic.

“Exosomes are suitable for targeted drug delivery because they are naturally designed to cross through biological barriers and are robust enough to withstand hydrolyzing enzymes in the blood and fluctuations in acidity and temperature that would otherwise break down the drug’s chemical bonds before it reaches the targeted organ,” Gourdie said. “By loading peptide drugs like alphaCT11 into exosomes, we’re seeking to protect the chemical integrity of the drug while guiding it to be recognized by specific cell types in the body – including those ailing in a heart attack.”

Once regarded as fatty waste disposal containers secreted by cells, exosomes emerged as a potential drug delivery method in 2007 when Swedish researchers observed cells releasing exosomes containing genetic material used to regulate protein synthesis and gene expression in neighboring cells. Over the past decade, research into their function, transmission pathways, and the potential pharmaceutical applications has surged.

Some scientists are developing artificial capsules to mimic exosomes, while others, like Gourdie and his team, are finding answers in nature.

Milk generated by nursing mammals is packed with exosomes, apparently to deliver important nutrients, proteins, and other signaling molecules from the mother to the nursing baby. Researchers expect exosomes derived from mammalian milk will be more easily absorbed and tolerated by patients than synthetic substitutes.

“Pharmaceutical companies have not been keen to develop drugs based on peptides, even when they show great promise in animal studies, as they are difficult to administer to patients and break down quickly in the body," Gourdie said. “Orally delivered exosomes from cow’s milk could provide a way to overcome both these barriers.”

Before it’s safe to proceed with clinical testing in humans, the scientists need to analyze the exosome’s stability and address potential immune reactions. Gourdie’s team is also analyzing ways to target exosome transfer so the medication-laden molecules are recognized and absorbed by specific cell types, enabling the drug to affect specific organs.

The drug is a new, more potent modification of a larger therapeutic molecule, alphaCT1, which clinical studies show can accelerate diabetic foot ulcer healing and reduce inflammation. It works by temporarily interrupting a cell signaling channel between cells formed by a protein called connexin 43.

Without functional signaling pathways, injured cells directly affected by the heart attack can’t influence surrounding healthy tissue to self-destruct, a phenomenon referred to by scientists as the “bystander effect.”

By limiting the spread of injury following a heart attack, Gourdie and his team expect the alphaCT11 drug and Tiny Cargo’s exosome packaging could one day lead to better patient outcomes.

Read this article on the Virginia Tech News website.