12 February 2009 University of Michigan

University Scientists Develop New Way to Treat People with Cystic Fibrosis

Thanks to a new treatment developed at the University of Michigan, adults and children suffering from cystic fibrosis may soon have a way to curb the fatal lung infections that are often associated with the disease.

John LiPuma, professor of pediatrics and communicable diseases at the Medical Schoo, and James Baker, director of the Michigan Nanotechnology Institute for Medicine and Biological Sciences, headed the group of scientists that discovered a new technique to kill resistant bacteria that colonize the lungs of people with cystic fibrosis.

Schematic of lungs.

“For unknown reasons, (the lungs of those with cystic fibrosis) get colonized with bacteria species that are very difficult to treat,” said Paul Makidon, a lab specialist who participated in the research as a Ph.D. student. “Once they get infected, these patients will develop second pathologies in their lungs, and these organisms are often pan-resistant to antibiotics.”

The researchers discovered a way to use a nanoemulsion — a solution of two high-energy liquids that do not mix, like oil and water — to treat lung infections.

“It's not entirely clear how this works to kill bacteria and other microorganisms, but the belief is that these very small droplets, which now pack a lot of energy, somehow fuse with and disrupt the membranes that hold microorganisms together,” LiPuma said. “It basically just blows microorganisms up.”

In the study, researchers tested nanoemulsion on 150 bacterial strains that harm those with cystic fibrosis. The results proved successful, as the treatment killed all of the strains, including one-third of those resistant to multiple antibiotics.

Baker said the drug they developed is unlike any other antibiotic because it physically interacts with the bacteria to disrupt its membrane. This kills the bacteria, eliminating the problem of bacteria resistance.

LiPuma said the leading cause of death in people with cystic fibrosis is lung failure.

“Ninety-five percent of people with CF die from respiratory failure, and that respiratory failure results from chronic and recurrent lung infections that eventually destroy their lungs,” he said.

The majority of lung infections cannot be treated with antibiotics currently on the market because bacteria in the lungs have become highly resistant to standard antibiotics.

“There's a need for novel antibiotics,” LiPuma said. “This nanoemulsion, at least in the test tube, is very effective against the types of bacteria people with CF get.”

The goal of the research, LiPuma said, is to make the nanoemulsion into an antibiotic that can be used in an inhaler.

Baker said nanoemulsion has been used in clinical trials for treating skin infections like cold sores, but it has never been used to treat lung infections.

Makidon helped evaluate the safety of using nanoemulsion inside organisms. His work included measuring the effects of nanoemulsion in test tubes and looking at how it could affect a living organism like an animal or person.

“I was involved in looking at how effective nanoemulsion is at killing the pan-resistant bacteria organisms and optimizing the platform itself while at the same time trying not to compromise the safety characteristics of the material,” Makidon said.

He said the new treatment “potentially could have an extraordinary impact on the well-being of patients with cystic fibrosis.”

The researchers have been developing the antibiotic over the past two years, and hope to make it publicly available within the next two to five years.

“Drug discovery takes a very, very long time and there are many hurdles to overcome and lots of obstacles in terms of getting a new drug from the bench, as we say, into patients,” LiPuma said.

Source: University of Michigan /...


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