Two babies have received the first-ever gene therapy for Tay-Sachs disease after over 14 years of development.
Tay-Sachs is a severe neurological disease caused by a deficiency in an enzyme called HexA. This enzyme breaks down a fatlike substance that normally exists in very small, harmless amounts in the brain. Without HexA, however, this fatlike substance can accumulate to toxic levels that damage and kill neurons.
One of the symptoms of this disease was first described in 1883 by British ophthalmologist Warren Tay, who saw a cherry-red spot on the back of the eye of affected infants. In 1887, American neurologist Bernard Sachs described the profound neurological symptoms of Tay-Sachs in a seminal paper:
“… Nothing abnormal was noticed until the age of two to three months, when the parents observed that the child was much more listless than children of that age. … The child would ordinarily lay upon its back, and was never able to change its position … it never attempted any voluntary movement … the child grew steadily weaker, it ceased to take its food properly, its bronchial troubles increased, and finally, pneumonia set in, it died August, 1886.”
This dismal description of Tay-Sachs remains current, and those with the disease usually die by age 5. Some people develop Tay-Sachs later in life, with symptoms starting in their teens that get progressively worse over many decades.
Patients with Tay-Sachs often have a cherry-red spot in the retina of their eyes.
Kateryna Kon/Science Photo Library via Getty Images
Unfortunately there is still no treatment for Tay-Sachs. Aggressive medical treatment can extend survival but doesn’t improve neurological function. The only effective way to treat Tay-Sachs is to restore the HexA enzyme in the brain. This is difficult, however, because the blood-brain barrier prevents most molecules from passing into the brain.
I am a member of a team of researchers from UMass Chan Medical School and Auburn University who developed a gene therapy that may help get around this barrier. Our treatment uses two harmless viral vectors to deliver DNA instructions to brain cells that teach them how to produce the missing enzyme. Similar techniques have been used to treat a number of related diseases and other conditions. In the case of Tay-Sachs, these DNA instructions enter the nucleus of these cells and stay there, allowing for long-term production of HexA. Based on our previous studies successfully testing our gene therapy on different animal species, we believe that delivering the treatment to a central part of the brain allows the enzyme to travel along its connections to other regions and to be distributed throughout the entire brain.
The first child who received our gene therapy treatment was age 2 ½, with late-stage disease symptoms. Three months after treatment, they had better muscle control and could focus their eyes. Now at age 5, the child is…