Jolie Krause and her parents faced her death many times during the first tenuous weeks of her life. The muscles throughout her small body were not working properly. her heart. her feet. her larynx. Even the involuntary movement of breathing was difficult, and I was constantly feeling light-headed.
In the midst of panicked days of terrible news and incomprehensible instructions, something unbelievable happened. A long-term attempt to find the root cause of her problems led to the identification of a widely available but previously unknown treatment.
“The results were very quick,” Joanie Kraus, Jolie’s mother, told the audience at STAT’s Breakthrough Summit West in San Francisco on Tuesday. Suddenly, she remembered that her child, who had spent 73 days in the neonatal intensive care unit and then faced developmental arrest for the first two years of her life, was able to move freely, avoid obstacles, look at a Fisher-Price toy, pick it up and say “(s)quare,” even without the s.
“I said, ‘No way,'” Joanie Krauss recalls. “That can’t happen and it can’t be this fast. It was like a light switch.”
The switch was probably Klonopin, a widely available muscle relaxant commonly used to treat seizure disorders and panic attacks.
The Mayo Clinic program discovered that Jolie was born with an extremely rare disease caused by a deletion of a gene linked to chromosome 10, causing her to suffer from a range of neurodevelopmental and motor symptoms. Doctors quickly sequenced her genome and used an artificial intelligence tool known as a biomedical data translator to identify Klonopin, a drug with properties that counteract many of the debilitating effects of the disease, from a vast database of available compounds.
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During the Breakthrough West Summit, Jolie’s parents sat with their almost 3-year-old child on her father’s lap to discuss ways to expand the technology and processes that give their daughter opportunities to grow.
“We don’t know the limits,” Jolie’s mother said, noting that Jolie has neurodevelopmental delays and will need lifelong care. “Guys, our child has been given a second chance at life!”
Whitney Thompson, the doctor who identified Jolie’s treatment with Mayo colleague Laura Lambert, said multiple barriers stood in the way of bringing such quick and effective treatment to other children with rare, undiagnosed conditions. One is that genome sequencing is not widely available. Another is the difficulty in conducting rapid clinical tests to identify potentially effective and available treatments.
But she said that through the course of Jolie’s treatment, important truths about the series of discoveries that saved her became unmistakable.
“I don’t think we could have gotten this far without the AI tools,” Thompson said. “You can make inferences across all the biomedical literature, and you can infer things that you wouldn’t otherwise be able to connect. So the AI part of this was really important.”
Its AI tool, Biomedical Data Translator, was built by a consortium of researchers with funding from the National Institutes of Health to create an open-source knowledge graph that can harmonize, integrate, and reason about disparate data sources. In recent years, it has been used to identify treatments for multiple patients with ultra-rare conditions, but ensuring consistent and reliable implementation across health systems in different regions is still a work in progress.
Jolie’s parents founded an organization called The Jolie Effect to provide funding and other resources to help children and families with the same condition. Jolie’s example is already beginning to affect children much older than her, whose development is stunted by similar gene deletions.
Joanie Kraus recounted the case of a patient several years older whose family contacted her on Monday. The child’s neurologist followed the same procedure used to treat Jolie and prescribed Klonpin, which produced a breakthrough effect.
“The child was 5 years old and received the same diagnosis, but with a different type, and went from not speaking to speaking in sentences,” Joanie said. “It’s huge.”
Jolie’s father, Dave Krause, said speaking publicly about his family’s experience is essential to potentially help struggling children and families. He said he feels that way even though doing so puts him in the worst moment of his life. That’s when, through beeping machines and a maze of wires, doctors told her that her son had a long time to live and that she might never be able to participate in the activity she was currently involved in: planning his third birthday party.
“The whole reason we keep talking about this is hope,” he said. “As long as someone listens, I’ll keep talking about this because parents need it.”
