Tay-Sachs disease is rare, but for patients and their families the disorder is devastating. Kids that are diagnosed tend to die by the age of five. The disease has been traced back to a mutation in a gene that encodes for the HexA enzyme, which has an essential role in the brain. HexA breaks down a lipid called GM2 ganglioside, which is normally found at low levels in the brain. While that fat-like substance is normally harmless, GM2 ganglioside can cause serious problems if it builds up, which happens in Tay-Sachs patients. But functional HexA enzyme can't just be given to them, because the majority of what's ingested doesn't get across the blood-brain barrier. So cells in the brain have to produce it, and if they cannot, the condition is fatal.
Gene therapy might be a way to cure Tay-Sachs disease, but this approach presents many challenges.
Scientists may have overcome those challenges. A team of researchers has now successfully treated two Tay-Sachs patients with an experimental therapy that contains the genetic instructions for creating HexA. The process uses a viral vector to get the HexA gene therapy reagents into the nucleus of cells, where the genome is. This treatment was injected into the brains of animal models to tests its efficacy. Those tests suggested the approach would work, and it was then tested on two people.
The first individual was 30 months old when they got the treatment, and showing late-stage symptoms of the disease. Three months later, the patient had regained some muscle control and was able to focus their eyes. The child is now five years old, and is seizure free and in stable health, which is typically not possible for a Tay-Sachs patient at that age.
Another child was given the treatment at seven months of age. After three months, this patient showed signs of improved neurodevelopment. At just over two years old, they are not having seizures.
The scientists involved in this effort noted that more research will be needed before we know if the treatment stops the disease from progressing any further. A larger clinical trial is now in the works to help answer that question and learn more about the dosage and any potential safety risks.