Breaking Ground in Gene Therapy: Eliza O’Neill’s Journey with Sanfilippo Syndrome

In 2015, the O’Neill family posed for a photo, capturing Glenn, Beckham, Cara, and Eliza O’Neill. Eliza, diagnosed with Sanfilippo syndrome, lives with a rare inherited disease. Her mother, Cara O’Neill, a pediatrician in Columbia, S.C., recalls Eliza’s childhood fascination with accessories like hats or scarves, and how she loved to wear her mother’s high heels. However, by age three, signs of developmental delays emerged.

The family initially thought Eliza had a pragmatic speech delay. She learned many words but struggled to use them socially. In 2013, a colleague of Cara suggested testing Eliza for metabolic disorders. The result revealed Sanfilippo syndrome, a condition Cara remembered from medical school. It is characterized by a faulty gene that prevents the breakdown of heparin sulfate, leading to severe complications. Children with this syndrome often lose the ability to speak and walk, suffer seizures and many do not live past their teenage years.

For Glenn O’Neill, the diagnosis brought a realization of the rapid progression of the disease. He knew immediate action was necessary. At Nationwide Children’s Hospital in Columbus, Ohio, researcher Haiyan Fu focused on developing gene therapy for the syndrome. Her work, beginning in the late 1990s, involved using a modified virus to deliver a functional copy of the gene to cells. Despite challenges, Fu’s efforts continued, supported by several patient foundations.

Funding a clinical trial, however, posed a significant challenge. Glenn O’Neill took a proactive approach by reaching out online, leading to the creation of a viral video by filmmaker Benjamin Von Wong in 2014. The video, “Saving Eliza,” broke GoFundMe records by raising millions, funding the first human trial in 2016. Biotech industry attention from these promising trials eventually led Ultragenyx to acquire the gene therapy rights in 2022.

By September, the FDA approved the treatment, named Fayuvi. Ultragenyx CEO Emil Kakkis highlighted the importance of early treatment, especially in very young children who have not yet experienced severe degeneration. Set at nearly $4 million, the treatment is among the most expensive gene therapies. However, Kakkis emphasizes Ultragenyx’s commitment to ensuring all patients can access it, regardless of logistics or cost.

Following the FDA approval, Fu received messages from families involved in the research funding. Some had tragically lost children. Fu acknowledges the bittersweet nature of the approval, noting the time taken to reach this stage. Eliza, now nearly 17, was the first child in the trial. Though she lost her speech ability and has not regained it, she communicates with picture cards and enjoys activities like swimming.

Glenn O’Neill expresses pride in Eliza’s resilience. Despite her struggles, her journey offers hope and underscores the importance of continued efforts in fighting such diseases.