Animal Alternatives

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For decades, drug discovery has relied on animals for testing the safety and efficacy of potential therapeutic agents, but that process has drawbacks. There are moral dilemmas, of course, related to the potential suffering of lab animals, but ethical concerns aside, animals are often poor physiological stand-ins for humans. Studies show that roughly nine out of 10 investigational drugs proven to be safe and effective in animals ultimately fail in human trials.

Hesperos, an Orlando company born out of the University of Central Florida’s business incubation program, has developed an alternative to animal testing for drug and cosmetics researchers with its patented “human-on-a-chip” system.

The plastic device, small enough to fit in the palm of your hand, integrates cells from different organs — such as the brain, heart, liver, pancreas and gut — with chemically patterned microchips. The system uses gentle rocking — gravity, essentially — to recirculate a blood substitute between the interlinked organ modules so they’re all exchanging information, similar to the way they would in the human body. Researchers can then measure functional changes in the mini-organs to better understand how the body will react to chemicals and novel therapeutics.

Pharmaceutical giants have taken an interest in the technology. Hesperos has worked with AstraZeneca using the platform to better understand the origins of cardiac toxicity of the allergy drug terfenadine, which was banned in the 1990s after it was found to cause fatal heart rhythms when used in combination with other drugs. And Hesperos has collaborated with Hoffman-La Roche Pharmaceuticals and UCF using a three-organ system to study immune responses.

Sanofi, a French pharmaceutical company, has used Hesperos’ human-on-a-chip technology to test an existing drug to see if it might help people suffering from chronic inflammatory demyelinating polyneuropathy (CIDP), a rare autoimmune disorder that causes nerve damage resulting in weakness in the arms and legs and trouble walking. It did, and that information coupled with safety data from prior studies allowed the drug to be repurposed into a phase two clinical trial.

“That’s a first. That had never been done before,” says James Hickman, a co-founder of Hesperos and a professor of chemistry, biomolecular sciences and electrical engineering at University of Central Florida, and he sees great promise for his company’s technology across the rare disease realm.

While there are more than 7,000 rare diseases, only a few hundred have active research programs investigating potential treatments, and that’s in large part because of no animal models. Current methods rely on creating inbred mice to tease out certain genetic traits, he explains, but they’re still a poor human surrogate.

Hesperos’ method takes actual cells from the patient with the rare disease, turns them into stem cells to differentiate out the relevant organs as they’d actually be in the person with that rare disease and then tests drugs on those miniature models to see which therapies work. The cherry on top — it can do all of that in a fraction of the time and at a fraction of the cost of conventional animal models.

Hickman believes that within five to 10 years, human-on-a-chip systems will eliminate the need for animal testing in most studies, except for those measuring systemic toxicity.

“We can reproduce things for toxicity that we kind of know about, but then there’s a last test that normally occurs, where you just put it into an animal and see what happens because there might be things you weren’t anticipating that happen, and I think it’s going to be almost impossible to reproduce that,” he says. “You’ll probably always need some animals for safety, but if we can decrease the number of animals for safety by 90%, I’ll be happy.”

Legislative Boost

The FDA Modernization Act 2.0, which was signed into law in 2022, has provided a boost to human organ-on-a-chip companies like Hesperos by authorizing drug companies to use certain alternatives to animal testing.

“They can actually substitute other systems, and (the law) called out micro-physiological systems by name, so now everybody is really saying, ‘OK, if the FDA and Congress are endorsing this, then the FDA has to accept this.’ Our company is growing by leaps and bounds at the moment,” says James Hickman, chief scientist at Hesperos and a professor at the University of Central Florida.

Hesperos (Orlando)

• ORIGINS: Michael Shuler, a biomedical engineering professor at Cornell University who coined the term “animal-on-achip” more than 30 years ago, and James Hickman, founding director and professor of the UCF Nanoscience Technology Center, began collaborating on multi-organ chip technology for drug development after meeting at a conference in 2009. They launched Hesperos in 2015, licensing roughly 20 patents from UCF and Cornell and “with a little bit of our own money,” says Hickman. They’ve sustained operations mostly through Small Business Innovation Research grants from the National Institutes of Health and customer revenue.
• GROWTH MODE: In 2019, Hesperos moved into a 14,000-sq.-ft. facility within Central Florida Research Park in east Orange County. The company has 45 employees, has grown revenue to more than $5 million a year and was profitable in 2019 and 2020. While COVID-19 “kind of set us back in terms of possibilities” over the past couple of years, Hickman says, revenue continues to grow, and the company is seeking investment money to expand.
• MISSION-ORIENTED: “Mike and I have never taken a dime of salary from the company. We’re not in this to make money,” Hickman says. “We want the company to make money — the company has to be successful. We believe it could help people. We’re already showing that it can help people.”
• ACCOLADES: Hesperos was the 2015 winner of the Lush Prize for Science, a project between the Ethical Consumer Research Association (a U.K.-based nonprofit) and Lush Cosmetics that recognizes groundbreaking work in animal-free testing methods. In 2022, BioFlorida, the state’s biotechnology organization, named Hickman its researcher of the year.

Tags: Healthcare, Feature