How do you toast a gene therapy trial? With tea.| NHGRI

How do you toast a gene therapy trial? With tea.| NHGRI

By Teresa L. Carey, M.A. It’s teatime and doctors, researchers and patients are at the table. They celebrate a decade of work and launch the first in-human gene therapy trial for children with a rare and devastating disease, GM1 gangliosidosis. Cyndi Tifft opened a bag and pulled out one of the items inside: a teacup. It was painted with colorful flowers, and gold trim adorned the rim. Written across the bag, in an 8-year-old’s scrawl, was "For Dr. Grandma. Thank you. Love, Jojo." Tifft was getting ready for Jojo's tea party of a lifetime. What would happen after, while young Jojo napped, would be the culmination of a decade of work and a new life for someone with a devastating disease. Jojo was about to receive the first experimental gene therapy treatment for the rare disease, GM1 gangliosidosis. Dr. Tifft, a geneticist at the National Human Genome Research Institute, first met Jojo in 2016. Jojo and her mother, Lei, arrived at the NIH Clinical Center with their tea set when they volunteered to take part in Tifft's natural history study. For 10 years, Tifft followed 35 children with GM1 gangliosidosis to see how the disease developed, hoping to gain insight into treatment options.

Jojo and Tifft host tea parties every time Jojo has an appointment. The tradition extended to the entire team on the day of the gene therapy trial. Credit: Ernesto Del Aguila

During her first visit, Jojo renamed all her doctors. She dubbed her six-and-a-half foot tall neurologist, "Dr. Big Shoes." By the end of the week, she called Tifft, "Dr. Grandma." When Tifft hears that name she beams. When Tifft met Jojo, she was walking, talking and writing. Now, three years later, Jojo needs help standing, speaking and just about everything else. She has a disease that attacks nerve cells in the brain, rendering them useless, one by one. When Jojo was born, GM1 gangliosidosis was already wreaking havoc on her neurons. At the time, no one knew.  Jojo inherited the genes for GM1 gangliosidosis from her mother and father. Though both parents are healthy, they each have a mutated GLB1 gene. With only one mutated copy, they are considered carriers, and are unaffected. GM1 gangliosidosis manifests in people with two copies of the mutated gene. Jojo inherited one from each parent. This inheritance pattern is called autosomal recessive. The odds of two carriers meeting and passing on their mutated GLB1 gene are slim; on average, only about one in 100,000 people has GM1 gangliosidosis.

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