When Angelina Cossey Dellacqua finally received the liver transplant her mother had fervently prayed for, the reality was bittersweet. By the time of the surgery, her health had significantly deteriorated, leaving her in a fragile state that required relentless medical support. Over the three weeks she spent recuperating in the critical care unit at Stanford Hospital, both her mother and her doctor remained faithfully by her side, cheering her on in her battle for recovery.
Dr. June-Wha Rhee, who was a cardiology fellow at Stanford Medicine at the time, recalls, “Angelina required maximal support and close care throughout the day and night.” She described Dellacqua as a once-healthy, vibrant young mother whose motivation to get better for her 3-year-old daughter was palpable. Despite her efforts, tragedy struck on October 19, 2015, when Dellacqua succumbed to acute heart failure—an unfortunate complication of an underlying disorder known as hemochromatosis. This condition causes harmful iron buildup in various organs, and when the surgeons removed her liver, it was discovered to be heavily damaged, showing signs of excessive iron deposits.
Vickie Dellacqua, Angelina’s mother, expressed her profound grief: “When my girl passed, I really just lost my mind. She was amazing—compassionate and constantly giving. She was a fighter, too; she told her doctors she didn’t want to leave.” In the midst of her pain, Vickie found solace in caring for Angelina’s daughter, Valentina, describing her as “my lifesaver.”
### Motivating Years of Research
The impact of Angelina’s story resonates deeply and has fueled Dr. Rhee’s continued research efforts to uncover potential solutions for treating conditions like hers. In a recently published study in *Cell Reports*, Rhee and her colleagues from the Stanford School of Medicine identified a drug called ebselen that may offer hope for patients suffering from iron-overload diseases. Rhee remarked, “This has the potential to someday be used in the clinic.” The drug, although not yet approved by the FDA, showed promise in blocking the entry of iron into human heart cells cultivated in the lab.
Dr. Joseph Wu, the director of the Stanford Cardiovascular Institute and senior author of the study, elaborated on their methodology: “We were able to use technology developed in our lab to demonstrate the mechanisms of iron overload in the heart.” Rhee and Wu’s team harnessed induced pluripotent stem cells to create cardiomyocytes—heart cells—that could provide a model for investigating various heart toxicities.
### Common Condition
Hemochromatosis is a surprisingly common but often misunderstood condition. It can result in severe multiorgan dysfunction, generally stemming from either hereditary factors or excessive iron input into the body, frequently due to repeated blood transfusions. In Dellacqua’s case, the excess iron accumulation in her heart was directly responsible for her heart failure.
While hemochromatosis can be treated through iron chelation therapy—medicinal approaches designed to remove excess metals from the body—this treatment is not viable for everyone. Rhee illuminated the challenges: “Chelation therapy is, unfortunately, toxic to the kidneys. Angelina’s liver disease had also led to kidney failure, making this treatment unsafe for her.” This predicament is more common than many realize.
### Investigating Iron Overload
To delve into the impacts of iron overload, researchers developed cardiomyocytes in the lab using stem cells, eventually forming them into tiny, three-dimensional spheroids resembling grains of sand. These cell clusters beat in unison, mimicking the natural function of a human heart.
Rhee emphasized the importance of this 3D model, explaining how iron diffuses within heart tissue. “The way you diagnose excessive iron accumulation in the heart is through cardiac MRI. In those 3D images, the heart appears black.” The researchers exposed the heart cell spheroids to rising concentrations of iron, observing the same darkening that signifies iron toxicity, leading them to uncover key insights regarding the disease’s molecular mechanisms.
### Exposing Heart Cells to Drugs
In a crucial phase of their research, the team tested various drugs on these heart cells to identify potential candidates for reversing the effects of iron overload. Ebselen emerged as the most promising option, demonstrating an ability to block iron entry channels and offering a protective effect against heart failure.
Throughout this project, which began about four years ago, Rhee maintained close communication with Dellacqua’s mother, keeping her updated on the findings and the hope that new treatments might emerge. Their discussions often touched upon the possibility that Valentina could inherit a genetic predisposition to hemochromatosis, accentuating the urgency of the research.
“I’m so sorry I had to lose my girl, but I’m so glad that they are doing research so that someone else can be alive today,” Vickie Dellacqua remarked. “I call it Angelina’s research. I never want anybody to forget her.”
Rhee’s dedication to this line of inquiry exemplifies Stanford Medicine’s commitment to precision health, which aims not only to diagnose and treat diseases but also to anticipate and prevent them from affecting future generations.