For most asthma sufferers, today’s inhaler drugs are helpful at calming attacks. But for about 10 to 15% of patients who have severe asthma, they don’t help much. These are the patients whose cases who end up in emergency rooms or intensive care units.
But an emerging technology that mimics the small airways in the human lung could soon help drug companies better understand the cause of these attacks and develop more effective treatments.
"There’s been a tremendous focus over the last few years in trying to understand why current [asthma] therapies do not work for this disease population, both looking for new therapies and also trying to develop new models that mimic the kind of response people have when they are exacerbating," says Michael Simon, principal scientist for immunology at the drug company, Merck.
Merck teamed with a startup Emulate, which spun out of Harvard University’s Wyss Institute for Biologically Inspired Engineering about one year ago. The company is working to commercialize "organ-on-a-chip" technologies, which are small flexible pieces of plastic that contain microfluidic channels lined with human cells (in this case of small airways in the lung). Designed like vessels inside an organ, they can mimic human systems more effectively than cells grown in a petri dish and help develop new drug targets and drug candidates. Ultimately, they might also offer a higher-fidelity alternatives to testing drugs in animals or the option to personalize disease treatments for individual patients.
For asthma and chronic pulmonary obstructive disease (COPD) specifically, using lab mice and rats offer poor analogues for humans. "There really is unmet need for models that can better predict human response," says Emulate CEO Geraldine Hamilton.
In a paper in the journal Nature Methods, co-authors from Emulate, Merck, and the drug company Pfizer published findings that showed the small airway lung chip could model the "complex tissue functions of the lung," including its response to anti-inflammatory drugs. It is somewhat unusual for two large drug companies to collaborate on research, but Simon said the research is needed and it is in a "pre-competitive" stage.
So far, Emulate has also teamed with Merck to develop an intestine-chip, to work on inflammatory diseases like irritable bowel syndrome. The startup is also developing other organ systems working with the drug company Johnson & Johnson and in other industries like food and cosmetics. One of Emulate’s goals is to make each chip automated and standardized, so researchers do not need special training to use it.
"If I test my drugs today in San Francisco, I need to be able to get the same results tomorrow in London," says Hamilton. For drug companies, says Simon, more data validation will be needed for that to be proven. Still, before then, he says, the chips will be useful for better understanding diseases and finding promising new drug candidates in the preclinical stage of drug development (i.e. before formal FDA testing).
"I think this is really excited work that will eventually change biotechnology and pharmaceutical research, and could change clinical practice, too," Simon says.