Novel peptide research offers waves of potential

Peptides used as drugs have been around for more than a hundred years. Insulin was the first peptide produced in a lab and has helped patients manage diabetes since 1923. Today, in Steven Bloom’s KU School of Pharmacy lab, the promise of peptides to treat disease states holds more potential than ever.

Bloom, assistant professor of medicinal chemistry, and his team of graduate and undergraduate student researchers are creating new peptides that could someday be used to stop viruses from replicating, improve stroke recovery, reduce obesity, or prevent neurogenerative disorders, such as Alzheimer's disease.

“It's a powerful technology, but it's also really simple,” said Bloom of the process he discovered to quickly exchange endogenous amino acids in peptides for ones made entirely in the lab. “We invented the platform to be easy enough that any student can do this, no matter the skill level. We have undergraduates do this, for instance. Our lab hosts a lot of undergraduate pharmacy students as well as some from the Chemistry Department. We’re kind of democratizing discovery in that way, so anybody should be able to use it.”

His lab has used cell-based models to test their peptides but have found chicken embryos to be a great model to explore, for example, how blood vessels respond in the presence of various drugs or diseases. Bloom has patented his “first in class” peptides used to expand blood vessels and keep them expanded longer than any known drug.

“We thought this could be really important in cases such as ischemic stroke when you have to restore blood flow. Widening the vessels allows blood to get into the brain to penetrate and pass through these areas of the brain that have been impacted. We patented that work, but all of that was tested and validated inside of the developing chicken embryo and you could quite literally watch and follow the expansion of the blood vessels.”

Bloom’s lab was not initially designed to do translational research for mouse or other models but he says now that they have an effective technology they know how to use, they are looking at moving into another phase of research.

“We know how to engineer peptides,” says Bloom, “and we're basically making things faster than we can use them right now. It's time to leverage the core facilities here—start accessing our engineered mouse models and take the peptides that we've discovered in our labs and translate them and move them forward. That's phase two (in our research) to apply our technology to translation work.

“The power of our chemistry is it also helps you to test new directions that maybe you wouldn't even know you should go in the first place.”

An example, Bloom says, is a peptide his lab created that enhances the efficacy of drugs like Wegovy® and Ozempic®—GLP-1 drugs or peptide therapies that successfully assist people with weight loss.

“Anytime you see these peptide pharmaceuticals, that's a place where our technology plugs right in to improve selectivity, improve potency, improve the stability in the body. We used our chemistry and found analogs that were five times more active than an FDA approved drug by quickly swapping native amino acids for synthetic ones in the peptide,” said Bloom. “That gave us a whole new direction to explore for optimizing analogs to make better drugs such as anti-obesity agents—something no one’s ever probed before.”

It will be years before Bloom’s research will be ready for human trials, but the potential impact is promising. Bloom’s lab is also targeting therapies for neurodegenerative diseases. Researchers have historically found drug therapies for these conditions to be elusive. The blood-brain barrier protects toxins from getting to the brain but makes it difficult for drug developers to get their molecules to specific places in the brain where they can treat and repair damage.

“I think our platform could be useful for central nervous system (CNS) active compounds where we can use our chemistry to find amino acids that improve blood-brain penetrance, dial in selectivity, bind better and actually get into the CNS,” Bloom said.

Bloom estimates peptides were approximately 10% of the FDA’s approved drugs in the last decade, but he sees a future of increasing importance for peptide therapies. Those that treat dietary obesity, for example, have become hot topics for researchers and these new avenues are what Bloom calls “perfect playgrounds” for his lab’s technology.