In her home on the island of Kauai with her husband Chris Constantino at her side and her two children playing nearby, Nichelle Obar breaks the illusion that nothing was ever amiss in her family’s slice of paradise.

“It all happened so fast,” she says, explaining the cascade of news and life-and-death decisions she and Chris had to make eight years ago. “We didn’t have many options. You’re just thinking, ‘we need to save our baby.'”

About midway through her pregnancy, Nichelle and Chris found out their unborn daughter had a rare genetic blood disorder. Most children with the condition die at birth or soon after. Until recently, doctors had little they could do, but CIRM-supported work at UC San Francisco offered another option.

The couple could let nature take its course or pursue an unproven therapy in a clinical trial. 

The couple has shared their story before, including on CIRM’s blog, but so far they haven’t shared how they see the clinical trial that didn’t achieve its goal of curing her baby. Scientists involved in clinical research emphasize that a trial that doesn’t achieve its primary goal can still deliver crucial insights about safety or feasibility or reveal potential biological barriers to a treatment. Those insights can, in turn, guide what to try next. For Nichelle and Chris, the trial did all of that. 

“The goal was a cure in the womb, but even though there was no cure, I think the treatment successfully brought out that there are other options for families like ours,” Nichelle said. 

‘You’d be the first’

A clinical trial is a crucial step in testing new medical treatments, therapies, devices, and drugs. It’s an intensive process with several steps, starting with testing whether a treatment is safe. Each phase follows a strict protocol that controls how the study proceeds. Once researchers determine a treatment is safe, they move on to see whether it works. Participants are volunteers and are informed of the risks before consenting.

The success or failure of any treatment going through this process hinges on people weighing the risks and choosing to participate. 

That decision, even in lower-stakes treatments, can weigh heavily on anyone, but in Nichelle and Chris’s case, so much was at stake, and they had to decide quickly. They carefully considered all their options—consulting other doctors—before signing up for the CIRM-supported clinical trial at UCSF. They also asked a lot of questions about the clinical trial, which involved their as-yet-unborn baby girl, Elianna, receiving the first-ever in utero stem cell transplant, aimed at curing her rare blood disorder, alpha thalassemia major. 

“I remember asking how many others had gone through the trial, and they said, ‘You’d be the first,'” Nichelle said.

Alpha thalassemia major

Up until 2018, almost all babies with alpha thalassemia major died before or shortly after birth. 

Treatment options for this disease are severely limited, generally requiring multiple rounds of blood transfusions or a bone marrow transplant, which requires immunosuppressive therapy. Normally, fetuses die in the womb, or the pregnancy is aborted because of the poor prognosis. 

About 1 in 16 people are carriers of a type of alpha-thalassemia, but only about 1 in 10,000 babies is born with the most severe form, alpha-thalassemia major. Babies with that form of the condition experience extra stress on the heart. That’s what happened to Elianna. The blood disorder impaired her body’s ability to produce hemoglobin, the molecule that transports oxygen. The result is that her heart had to work much harder to transport oxygen through her body. The effort enlarged Elianna’s heart, and she developed fluid around it, a condition known as hydrops, which can lead to heart failure. 

Just as they learned that their daughter was in danger, Nichelle and Chris learned of the clinical trial at UCSF that offered another option. 

Five transfusions and one bone marrow transplant 

At the time, doctors had started treating unborn children with the condition with blood transfusions. Beyond that, researchers led by UCSF’s Tippi MacKenzie, MD, had just developed a new approach using stem cells that they hoped could cure the condition. 

After extracting stem cells from Nichelle’s bone marrow, the researchers transplanted them into the baby while she was still in the womb, hoping the stem cells would mature into healthy blood cells and treat the genetic condition early, while the baby was still developing. That kind of early treatment before birth would counter the possibility of rejection of a stem cell transplant. The transplant would occur while the unborn baby was also receiving blood transfusions, which had begun to be an approach for treating unborn children with alpha-thalassemia major.

There was much hope for this innovative approach, and the trial showed that both in utero blood transfusions and stem cell transplants could be done safely. Unfortunately, the stem cell transfusion didn’t cure Elianna’s blood disorder. However, the five blood transfusions helped stabilize Elianna during the pregnancy, allowing her to be born healthy, although premature. That in and of itself was a huge success, her parents said. The whole process also raised awareness around the condition and options parents in similar circumstances might have.

“I think it helped raise awareness of these other options, especially here in the islands,” Nichelle said.  

It also advances scientists’ understanding of how to treat not just this rare blood disorder but other genetic conditions before birth, she said.

Today, Elianna, 8, requires monthly blood transfusions, but she’s thriving and loves playing with her brother and going to school. 

Future treatments

Recently, Dr. MacKenzie and her team published the clinical trial results in the journal Blood Advances, including more than 5 years of observation after the initial stem cell transplant. 

“We developed a safe and feasible protocol for maternal hematopoietic stem cell transplantation during pregnancy,” the researchers said in their paper. 

Although the stem cell transplant didn’t cure Elianna’s condition, the clinical trial “results highlight fundamental biological barriers in this disease context and inform the design of future prenatal transplantation strategies in other disease settings such as Fanconi anemia.”

MacKenzie’s team continues to develop other approaches, including postnatal transplantation or gene-based strategies.

In 2025, a team at UCLA led by Dr. Donald Kohn—another pioneering CIRM-supported scientist—built on Dr. MacKenzie’s research to treat the condition.

“This work really began when Dr. Tippi MacKenzie, a pediatric surgeon at UC San Francisco who was treating these cases, reached out to us,” said Kohn, a distinguished professor of microbiology, immunology, and molecular genetics and a member of the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA. “She recognized that our gene therapy approach could be exactly what these children needed.”

Gratitude

Eight years later, Nichelle and Chris don’t dwell on what the clinical trial did not achieve.

“We went into knowing nothing was guaranteed,” she said.

Now their daughter is thriving.

Beyond that, she draws comfort in knowing that other families like hers have more options and hope.

“Our news got out there and opened the door, especially here in Hawaii (for other parents),” Nichelle said.