The National Institutes of Health (NIH) held its annual Rare Disease Day event on March 1, 2021 this year. This event showcases groundbreaking research, amazing rare patient stories, and more. One rare story presented that day touched on the potential of gene therapy as a breakthrough treatment for many different rare diseases. Gene therapy is still a relatively new method of treatment, but there are a few on the market and many others that are in various stages of development.
Cynthia J. Tifft, M.D., Ph.D., Deputy Clinical Director of the Office of the Clinical Director at the National Human Genome Research Institute (NHGRI), introduced the story and the disease that is at the center of it: GM1 gangliosidosis.
About GM1 Gangliosidosis
GM1 gangliosidosis is a group of inherited sphingolipidoses which are characterized by progressive damage to the nervous system along with other, severe effects. This is the result of abnormal lipid storage in cells, which is linked to a deficiency of beta-galactosidase. The disease is caused by mutations affecting the GLB1 gene. There are three different forms which are distinguished by when symptoms appear. Symptoms include neurodegeneration, seizures, muscle weakness, skeletal abnormalities, coarse facial features, enlarged liver and spleen, gait abnormalities, exaggerated startle response, joint stiffness, speech problems, dementia, and dystonia. There are no disease modifying therapies for GM1 gangliosidosis; in the most severe, infantile-onset form, patients rarely survive for more than a few years. In all cases, life span is significantly affected. There is an urgent need for more effective treatments. To learn more about GM1 gangliosidosis, click here.
The Flysjö Family Story
Parents Niclas and Jessica Flysjö, who have three children with the type 2 late-infantile form of the disease, first noticed symptoms at around age one or two. Their children are involved in an open-label study that is investigating a possible gene therapy treatment for this deadly disease.
“The gene therapy was administered to the three children on April 28, 2020, after a long and arduous journey that required them to stay at the NIH for seven months.” – Dr. Tifft
Niclas and Jessica noticed problems like loss of balance and delays in speech development. However, they weren’t able to get a clear answer on what was going on for a long time:
“For a year and a half, they went through test after test, but we didn’t get any answers, which was very frustrating.” – Jessica
The parents were distraught when they finally received the diagnosis and sought support from the community around this disease. Their search led them to the Cure GM1 Gangliosidosis Foundation. It was here that they first learned about the possibilities of gene therapy. This was there only source of hope as they learned that their newborn twins also had the illness. After facing another hurdle of tests to get into the trial, the COVID-19 pandemic almost prevented them from participating. They arrived in the US only three hours before travel from Europe to the US was shut down (the family is originally from Sweden).
“Despite being so far from home, we felt safe at the NIH campus. We finally were able to begin the return trip home on November 2nd.” – Niclas
“While we think it’s too early to tell if the therapy is working, there are days that the kids struggle and days that they do things that surprise us in a very positive way.” – Jessica
The circumstances surrounding gene therapy trials are always a bit risky, and the family’s experience was even more so in the midst of the pandemic. Niclas says that these risks are something that families interested in these trials must weigh. While it isn’t what the outcome will be for this rare disease family, gene therapy is giving them a source of hope when before there was none.
