A new way to kill superbugs

Nitric Oxide plays a vital role in the body’s natural immune system response to pathogens. Vast Therapeutics is a pharmaceutical company in RTP using nitric oxide to develop new drugs to combat infections.

It’s a little frightening to stand in front of a lab door at the offices of Vast Therapeutics in Research Triangle Park and read the signs. “Dangerous pathogens, do not enter” one sign reads. “Protective clothing required” is printed on another.

“These are the bad bugs, well actually all of the bugs are in here,” says Rebecca McDonald, Senior Microbiologist with Vast Therapeutics. “These are the kind of bad bugs, but then there are the really bad bugs."

But then she asks if I wanted to see them. Being a reporter, I said yes.

McDonald puts her safety equipment on and tells me I can’t go beyond the warning line at the door. Then she takes several samples out of a secure refrigerator and shows them to me.

“These are bacteria that are growing, and if the color is orange it means the bacteria are living happily and if it is blue that means a drug candidate has killed the bacteria,” McDonald explains.

There are several areas on the tray that are blue. “Our goal, of course, is to kill the bacteria,” McDonald adds. And after thousands of experiments, researchers at the company believe they have found a super drug to kill super bugs.

The key ingredient is a simple molecule; nitric oxide. Your body already makes and uses this chemical compound as part of the natural immune system.

“We’ve killed almost 100 different bugs and super bugs, pathogens, and bacteria on our way to rolling this out and helping to combat those things antibiotics can’t do right now,” said Neil Hunter, CEO of Vast Therapeutics. “Your body already makes nitric oxide and it makes a lot of it but it just doesn’t put it into places that might be an area of need.”

Hunter cites the example of a cystic fibrosis patient with an infection in the lungs. Most treatments can’t get through the mucus and biofilm buildup that already creates a host of problems. Complicating measures, bacteria grow in the nasty environment. The company’s tests show nitric oxide can penetrate the mucus and biofilm to treat the infection. That’s why a cystic fibrosis drug is the medicine to begin drug test trials.

“The great thing about our medication is where you are delivering it is where it will end up acting,” said Mark Schoenfisch, PhD, President & Chief Scientific Officer, Vast Therapeutics. “This is a way to act locally on bacteria and do so in a way that does not negatively impact healthy cells and tissues.”

Schoenfisch shows me an atomic force microscope slide of bacteria before and after exposure to nitric oxide. The cells are oval shapes and solid in the first slide, but the cells look like a shotgun shell had blasted them afterwards.

“It’s part of the reason we call nitric oxide a smart bomb,” Schoenfisch said, smiling, as he looked at the image. “It attacks bacteria in multiple ways.”

The idea of using Nitric oxide as medicine isn’t new. That’s because it is naturally in the body so there’s less chance of the body rejecting it as well as a negative side effect. But the challenge for the company is that nitric oxide is a gas. It’s also difficult to deliver large amounts of nitric oxide into the body.

Scientists have found a way to dissolve the gas into a solution and link it to a solid molecule. Then large amounts of nitric oxide are delivered into the body to fight infections and the gas is released over time.

“So our different drug candidates have different carrier molecules, that have different profiles and different rates at which the medicine is absorbed,” adds McDonald. “So for different indications one might be better than the other.”

The company is testing nebulizers as a way to deliver medicine to cystic fibrosis patients. Other delivery methods will be tested later. The nebulizer delivers particles ranging from one micron to ten microns in size. To give you an idea of how small that is; the human hair is about 40 to 100 microns in diameter. “

That size is critical because we want these particles to go inside and treat the disease inside the lungs,” explains Schoenfisch. “And to get that deep penetration, we need the particles to be in the range of 10 to one micron. So you need a small particle, you need the right mass, and if you can control those two factors, and you have the right velocity of the person breathing, the medicine will get deep penetration into the lungs to treat the infection.”

Meanwhile, McDonald continues her battle against superbugs. “When I first was hired they asked me to keep testing our drugs against this bacteria and that bacteria,” McDonald recalls. “So I went in and tested my favorite pathogen and I said wow, it killed it really well. And the next week I tested another and it killed it again. And I started thinking, we’ve got something really good.”