Glycogen storage disease type 1a or GSD1a is a disease affecting the storage of glycogen, a complex carbohydrate with slow digestion, which serves as a sugar and energy reserve, mainly in the liver or the muscles. This rare disease affects one birth in 100,000 and may cause significant metabolic disorders, as well as certain types of cancer.
What is GSD1a?
GSD1a is the acronym for glycogen storage disease type 1a. It is caused by a mutation on the G6PC1 gene, which plays an important role in the release of sugar into the bloodstream, and affects 1 person in 100,000, with a much higher frequency in certain populations.
In the liver, glycogen is used to create glucose and keep the level of sugar in the blood (glycemia) stable between meals. In people suffering from GSD1a, the body cannot use glycogen to produce glucose, which causes very severe hypoglycemia, sometimes leading to coma or even death of the patient within a few minutes. Aside from hypoglycemia, symptoms often include hepatomegaly (abnormally enlarged liver due to glycogen storage), metabolic disorders, kidney problems, sometimes delayed development and liver cancer.
There is currently no curative treatment for this disease. Patients must constantly monitor their glycemia to prevent hypoglycemic seizures, and must follow a special diet, eating every 3 or 4 hours, including at night. When the liver is very damaged by the disease a liver transplant may be needed.
Genethon’s role in GSD1a
For several years, the Immunology and liver diseases team, headed by Giuseppe Ronzitti, has worked closely with Fabienne Rajas and Gilles Mithieux, from the Inserm U1213 unit based in Lyon, to develop a gene therapy product to treat this disease. The Lyon-based team has developed a viable model of mice with this disease, while Genethon has worked on developing the gene therapy product.
Sickle-cell disease today
The teams of Giuseppe Ronzitti and Fabienne Rajas now have proof of concept of the effectiveness of a gene therapy product in the mouse model to prevent hypoglycemia and the occurrence of liver tumors in the long term. A dose study in the disease model is currently on going and the next step is to launch toxicology studies to assess the safety of the product in animal models. Once preclinical steps have been completed, if they are conclusive, Genethon may submit a clinical trial authorization request to assess the effectiveness and safety of the product in humans.
