More than 100 Americans died yesterday from misuse of opioid drugs, and at least that many are likely to join them today.

The brisk pace of deaths from the misuse of opioid drugs has prompted national soul-searching about how to arrest this uniquely American phenomenon, which contributed to the deaths of 47,600 Americans in 2017, including 17,000 who took legal prescription opioids.

Stemonix, a 40-employee biotech firm in Minnesota that grows tiny globs of brain, may hold the key to a potential solution.

The Maple Grove-based startup company has been selected to join the federal HEAL Initiative, working specifically with the National Center for Advancing Translational Sciences (NCATS) in the National Institutes of Health to test a variety of chemical compounds with its microBrain 3-D test and develop a working model for how human brain cells respond to opioids. If successful, Stemonix’s stem-cell-based platform could be used to screen thousands of compounds to see if they could work as less-addictive painkillers.

NCATS’ goal “is to find the best model to advance new discoveries,” Stemonix co-founder and CEO Ping Yeh said. “It turns out that the human microBrains that we make from iPSCs have receptors to the opioid [compounds], and can be used as a model to find other potential therapeutics that are less addictive and have less issues like withdrawal symptoms.”

IPSCs stands for “induced pluripotent stem cells,” which means that Stemonix’s stems cells are developed from skin tissue, not human embryos. A Stemonix microBrain 3-D kit is composed of hundreds of tiny spheres of brain tissue, each about the size of a poppy seed and created under uniform conditions. The plate includes 384 little “wells,” each containing a spheroid of brain cells that includes a mix of different neuronal subtypes and astrocytes.

By closely monitoring what happens when different chemical compounds are added to each well, researchers can tell whether the cells are reacting chemically. By monitoring a process called “calcium signaling” in the brain cells, researchers hope to be able to develop a signature opioid-response model that can be proved out in efficacy testing.

If successful, that model could be then used to screen many different potential drug compounds for the signature opioid response, allowing researchers to predict which compounds could be promising drugs and which should be avoided.

The agreement between Stemonix and the NCATS doesn’t allow the company to disclose how long the collaboration will last or the expected budget, said Ryan Gordon, vice president of business development and commercialization at Stemonix. The first milestone in the agreement, expected to be completed this summer, is finishing the preliminary analysis to isolate a signature opioid response in the microBrain 3-D model.

The project is part of the larger federal HEAL Initiative to deter misuse of prescription opioids, but Gordon said it’s too early to say if microBrain cells would react differently to an illegal opiate such as heroin, compared with legal opioids such as OxyContin, Vicodin, fentanyl, morphine, and methadone.

“The phenotypic signature of these compounds in our microBrain model may differ,” Gordon said in an e-mail. “Ideally, we would like to see one phenotype emerge, that could be applied across a range of opioid chemistries (that would make subsequent screening and analysis much simpler). We’ll see if that happens.”

HEAL, an acronym for Helping to End Addiction Long-term, is a wide-ranging program at the National Institutes of Health based on 26 different research projects, from promising ideas to concrete strategies, that can reduce opioid-related deaths. It’s been described as an “all hands on deck” approach to the opioid crisis.

In 2019, NCATS had a $40 million budget for human-based screening platforms and novel drugs for pain and opioid use disorder, only part of which is going toward the collaboration with Stemonix. The goal of the project is to find a screening platform for drug leads that is more accurate than the animal experiments and cellular models that are widely in use today.

Part of NCATS’ mission is “pressure-testing” of promising new technologies, said Marc Ferrer, leader of biomolecular screening and probe development for center.

“In general, there is a huge push toward what people call ‘3-D tissue’ technologies for drug discovery,” Ferrer said, “in the hope that these 3-D tissue models represent … more predictive models in which to test compounds. It’s not only for opioids. There is a huge push for more relevant assays to do drug discovery and disease modeling on. And the work that Stemonix is doing is part of that.”

If that sounds like work that a commercial drug company like OxyContin maker Purdue Pharma could be doing — it is, Yeh and Gordon said. The microBrain technology hasn’t been used in this way yet because it’s so new, and one of NCATS’ larger goals is to advance the translation of new science into practical applications in industry.

“Human-based stem-cell biology opens up an opportunity now to look at functional impact of compounds on the actual biology going on in the brain, or within a certain cellular model of the brain, if you will,” Gordon said. “This is new. It’s an emerging industry. These are cutting-edge techniques and tools that really people haven’t had access to before.”