A six-year-old girl, referred to as Mei, died after her parents paid approximately $860,000 USD for an experimental gene therapy to treat her genetic developmental disorder. The treatment, a form of base editing, had not been used in humans before, according to a report in Science.
Mei had a rare mutation in her CHD3 gene, which is linked to intellectual disabilities and impaired speech and language. Although her case of Snijders Blok-Campeau Syndrome was considered mild and not fatal, her parents pursued the experimental therapy. The lead researcher, Zilong Qiu, reportedly expressed an ambition to publish the first brain-directed gene-editing therapy in a prestigious journal.
Questions are being raised about research oversight and the ethics of conducting trials on vulnerable families with unproven science. Steven Gray of the University of Texas Southwestern Medical Center, who develops viruses for gene therapy, stated, “This shouldn’t have gone to trial.” He and other experts are calling for a review of the data and images in a Nature paper published by Qiu earlier this year, which does not acknowledge Mei’s case.
Qiu's team claimed the base editing therapy was effective in mice, and provided images of monkey brains that they said demonstrated the therapy reached all regions. However, experts reviewing these images expressed doubts, with one biochemist suggesting they were unconvincing and potentially just background staining. Furthermore, a month before Mei's treatment, all four monkeys that received the therapy developed moderate to severe liver damage, and one showed signs of kidney damage consistent with thrombotic microangiopathy, a potentially deadly reaction to AAV therapy.
Despite these findings, Mei's parents were assured the treatment was "relatively safe," with the primary risk being the presence of antibodies to the viral vector. In March, Mei received the therapy, which involved injecting trillions of viruses into her spinal canal. Within days, she developed a persistent fever and stopped urinating, indicating kidney problems. She was admitted to the ICU and died the following day. An ethics board at the hospital determined her death was caused by the treatment, specifically thrombotic microangiopathy.
The hospital was fined around $3,600, and the doctor who described the treatment as "relatively safe" received verbal counseling. Mei’s parents asked Qiu to withdraw his Nature paper about the case, and though he initially agreed, he later ceased communication. Nature published the paper in February without mentioning Mei. The journal informed Mei's parents that ethical issues were outside their purview and should be handled by the university. Shanghai Jiao Tong University School of Medicine, where Qiu is affiliated, announced it would conduct a comprehensive investigation and take serious action based on its findings.