Rutgers scientists have developed a small research model that will help improve the understanding and treatment of lung-related illnesses like asthma. The technology, called a "bronchi-on-a-chip," mimics lung cells and can be used to test potential medications more efficiently than traditional animal or petri dish models.
The study, led by Dr. Reynold Panettieri of the Rutgers Institute for Translational Medicine and Science, was recently featured on the cover of Nature Biomedical Engineering.
Asthma, a disease that affects more than 1 in 20 Americans and currently lacks a cure, has two mechanisms, he said. First, there is airway inflammation in asthmatic lungs, a similar process to when you cut your hand and it turns red. Second, the smooth muscle surrounding the air tubes in the lungs is over-responsive and contracts more frequently, causing shortness of breath, coughing and wheezing.
“To treat asthma, you really have to use an anti-inflammatory, or something that quells inflammation like an inhaled steroid. You also need to use a bronchodilator, or something to relax that muscle,” Panettieri said.
As it stands, there have been no new medicines or bronchodilators used to relax the lung’s smooth muscle in more than 45 years. Panettieri said this is because studies have not focused on lung tissue specifically.
“Our study addresses this need because we can now study single-cell contraction of the airway's smooth muscle on the order of tens of thousands of cells,” he said. “So, what we can do now is look for novel compounds because we can make so many observations to find new ways of relaxing the muscle that'll become new drugs. This study we did has now defined a brand-new platform, a unique platform for drug discovery to relax the muscle in asthma.”
The key is something called the bronchi-on-a-chip, Panettieri said.
“(The chip) is a fraction of the size of a strand of hair and we populate it with cells that line the tube of the airway and the muscle beneath it. We are growing the primary cells that regulate the function of the bronchi on the chip to study them. We’re not growing lungs or bronchi, but we're leveraging the cells that actually are the important cells,” he said.
This model is better than current research models because of its efficiency and accuracy, Panettieri said. The bronchi-on-a-chip technology is cheaper than growing cell cultures on petri dishes and is more efficient because of its increased throughput. Animal models, he said, also fall short in discovery for asthma drugs because animals and humans have fundamentally different muscle tone and function in their lungs.
While the majority of patients currently treat their asthma with a rescue drug called albuterol or bronchodilators that serve as long-term maintenance therapy, Panettieri said these kind of drugs — called beta-agonists — can cause tolerance problems.
“The overuse of beta-agonists decreases the ability of the medication over time. It desensitizes or induces tolerance to the drug and makes it so that the drug doesn’t work,” he said.
The team’s approach, as a result, is to develop a bronchodilator that will not stop working even if it is overused. It would be more efficient and more effective, Panettieri said, being used less frequently to get the same benefit as current medications.
The study required the efforts of multiple teams of researchers from Rutgers University, Yale University and Johns Hopkins University.
“Science is complex, and the more complex means you need a lot more hands to do the work and you need a lot more of the brain power to do the work. What we did is build a collaborative team of scientists, each bringing unique expertise to the solution,” he said.
Within the next two years, the scientists hope to screen more than 100,000 molecules or potential drug candidates to find their new bronchodilator. After finding something that works, Panettieri said, you may have to verify its function in an animal model and use medicinal chemistry to optimize the chemistry of the drug.
“There's a lot of work even after finding a particularly good candidate. After that, to get it into clinical trials to get into patients could take anywhere from 5 to 6 years. The work that we're doing now may not bear fruits in the real medication for quite some time,” he said.
It is not much different from the process of becoming an independent research, Panettieri said, which can often take approximately 15 years.
“It's a long commitment, but there’s never a day I go to work because I love what I do. For me, it’s the novelty, the investigation — looking into things that have never been explored before, and the medicine that thrills me. If I had to do it all again, I would certainly do what I do," he said.