Advanced cell therapy study seeks transformational change in the way we treat infant brain injuries

April 5, 2019

This is part 3 in a series on CTSI-funded research to improve neonatal care. Read Part 1 here, and Part 2 here.

Michael Cotten, MD

In his time at Duke, Dr. Michael Cotten has found that sea-changes in medicine don’t always begin in the lab or the clinic. Sometimes an idea takes root in a more unexpected venue—like the sidelines of the Durham Girls Soccer League, where parents gather to watch their kids play.

“I’ve made amazing scientific connections just watching soccer games and getting into conversations with the other parents,” says Cotten, who is Chief of the Duke Division of Pediatric Neonatology. “It speaks volumes about the environment we’re in at Duke, and in Durham.”

As a neonatologist, Cotten has made the most of that environment, dedicating more than 15 years to collaborative research on the health challenges of newborn infants. In that time he’s led multiple clinical trials on the treatment of neonatal brain injury.

While much progress has been made, Cotten says, “We think we can do better.”

Stem cells from umbilical cord blood are an emerging therapy for repairing the damage caused by brain injuries like stroke and hypoxic ischemic encephalopathy (HIE). Experimental treatments using autologous cells, from the child’s own cord blood, have been underway at Duke for more than ten years.

However, most children are born in sites where cord blood collection is not routine, and arrive in the NICU with their own cells not available—what about them?

That question is driving a new effort to develop an “off-the-shelf” product that could make this kind of stem cell therapy much more widely accessible. Cotten is co-Principal Investigator with Dr. Joanne Kurtzberg—a stem cell therapy pioneer—and the project is receiving support from Duke CTSI Accelerator for a Phase I study.

While HIE is relatively rare in the United States, occurring in about 3 out of every 1000 live births, it is more common in premature infants, and its effects are serious: In moderate and severe cases, HIE can cause lifelong cognitive and motor impairment.

“We’re talking about several thousand kids a year that could avoid a lot of heartache and a lot of challenges in life if a comprehensive therapy were available,” Cotten says.

The cell therapy advantage

At present, there’s only one clinically validated and FDA-approved therapy for HIE: cooling. By lowering the baby’s body temperature, doctors have found that they can save lives and reduce the rate of serious impairment.

But cooling by itself can only do so much. “The cooling treatment is only for three days following diagnosis,” Cotten says. “Our goal to provide a positive environment for development of the brain in the days, weeks, months, and years after the injury.”

Multiple investigators around the country are exploring “cooling-plus” treatments—in other words, supplemental approaches that can create better outcomes for these children and their families. Duke is uniquely placed to test cell therapies, Cotten argues, in large part because of the presence of Dr. Kurtzberg, whose lab has been at the leading edge of this field for more than 25 years.

Their proposed treatment involves giving infants an infusion of allogeneic cells—cells from a genetically-matched donor—hopefully with similar positive effects to their own cells.

Ultimately, if these kinds of cells could be used safely and successfully to promote brain development, it could have a far-reaching impact on babies with perinatal conditions worldwide. This Phase I study is the first step toward that reality.

Safety first

Joanne Kurtzberg, MD

Cotten, Kurtzberg, and their clinical team will test the therapy with a small cohort of babies in the Duke NICU whose own cells are not available, and will mainly be concerned with tolerance and safety.

Families much like those in Part 1 of this series have a crucial role to play as participants in this study.

“We acknowledge that this is the first time we’re giving this kind of product to this kind of patient,” Cotten says. “We make the families aware of that, and we know we’re asking a lot of them to venture into the unknown.”

He emphasizes that safety is the primary focus. “In clinical research, our approach is not just ‘do no harm,’ but ‘do good.’”

They hope to see infants emerging from this trial without adverse effects such as graft-versus-host disease, in which the donor cells attack health tissue and organs. Cotten is optimistic on that issue, since the type of mysenchemal stromal cells they’re using are actually known to combat graft-versus-host disease.

If the safety indicators are good, they will proceed to a Phase II study to get more safety data and preliminary findings on efficacy—all part of the rigorous process to ensure that the final product can make a profound, positive difference in people’s lives.

“We’re tremendously excited to do this,” Cotten says. “If you multiply the potential impact by a child’s lifetime—sixty, seventy, eighty years—it’s huge.”

In Part 1 of this series, we heard the moving stories of parents whose children were born prematurely and received treatment in the Duke Neonatal-Perinatal Research Unit.

In Part 2, we saw how a dramatic life event and a lucky break helped Dr. Eric Benner discover a potential cure for infant brain injuries in breastmilk.