To really understand opioid addiction, researcher Ming-Fen Ho is getting down to the cellular level.
“If we have a better understanding of biology, then we can develop better drugs to treat the disease,” she said.
That's where the tiny bits of brain tissue — nicknamed mini brains — come in.
Ho, who has a PhD and is a stem cell biologist, is studying these specks of tissue, some no larger than a pinhead, because they could answer some vexing questions about addiction — like why some people suffer from it and others don't or why some respond to drugs meant to treat addiction and others don't.
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Ho’s work is motivated by the scope and scale of the opioid epidemic. In 2021, opioids were linked to 100,000 deaths, according to the Centers for Disease Control and Prevention. Often, prescription opioids used to treat pain were involved.
“It’s a national crisis. So many people die from opioid overdose,” she said. “When we started this study, the idea was of how we better treat those patients.”
Her work also signals a relatively recent shift in how medicine perceives addiction, said Dr. Richard Weinshilboum, who is working with Ho on her research.
For instance, Weinshilboum said he's old enough to remember a time when breast cancer wasn't discussed much in medicine.
"Now, of course, we're running marathons, and everyone wants to do something to help with this terrible disease,” he said.
Addiction is a disease that should be studied and treated as one, too.
“I think we're hoping that by understanding the disease better, we will be able to prevent addiction, just as we now do with breast cancer,” he said.
A unique partnership
Ho's research is in partnership with the Hazelden Betty Ford Foundation, a leading addiction treatment center. She uses blood samples donated by people diagnosed with opioid addiction being treated at Hazelden.
As medicine has shifted to view addiction as a disease, it's opened the door to novel research — including Ho's, said Quyen Ngo, who is executive director of Hazelden's Butler Center for Research.
“We're really looking at biological factors in treating addiction: How do we use that information to enhance our treatment, to improve our treatment at the biologic level and also at the behavioral level,” she said.
And it's prompted the broader health care community to also adjust its view.
“Our understanding of addiction as a chronic disease rather than an acute ‘one and done’ disease has really changed the way that we treat addiction, talk about addiction and understand addiction,” Ngo said.
The research promises to help people in her field better understand addiction on the cellular level, said University of Pennsylvania School of nursing professor Peggy Compton. But she says addiction is far more complicated because it also involves environmental factors, such as childhood trauma.
“Something as complex as addiction is difficult to understand by reducing it down to a certain lobe of the brain in a teeny tiny pea size organoid,” she said. “With a disease like addiction, people come to it through very different pathways.”
A painstaking process
Back in her Mayo lab, Ho explained how her research works. Using an array of equipment — some that she's built from scratch using 3D printers — Ho coaxes cell samples to develop into brain cells from the specific parts of the brain associated with addiction.
Over weeks and months, they grow, marinating in a nutrient culture to support their development.
And they spin in tiny custom vials that look a bit like blenders to form the right shape. It's a painstaking process, Ho said.
“The brain is 3D. This is why we need to use this instrument to constantly spin in the cultural media, so the cells in the center have access to those nutrients,” she said.
Among her findings so far is that individuals appear to respond to opioids and treatments differently on the cellular level, she said.
And, she said, that's what makes her model so useful — you can't just extract someone's brain tissue and study it.
The model can be extended to a variety of other types of addiction, Ho said.
“Right now we study alcohol addiction, cannabis use disorder, opioid use disorder, in addition to depression or bipolar, many other different types of neuropsychiatric disorders,” she said.
She says she hopes her findings someday lead to new drugs to treat addiction, and new tools for prevention.