Success, albeit modest
Gene therapy helped children with hereditary Thea disease — Sachs get rid of seizures
Anastasia Kuznetsova-Fantoni, N+1
American doctors with the help of a viral vector made up for the deficiency of the enzyme hexozoaminidase A in children with Tay—Sachs disease. The doctors told about the success of the treatment in Nature Medicine (Flotte et al., AAV gene therapy for Tay-Sachs disease).
Tay—Sachs disease is a hereditary disease that occurs due to mutations in the HEXA and HEXB genes that encode subunits of the enzyme hexozoaminidase A. This enzyme utilizes gangliosides in the central nervous system, therefore, in its absence, gangliosides accumulate in neurons, destroying them. In sick children, hearing and vision decrease, general development slows down and seizures occur periodically.
To date, there has been no specialized treatment for this disease. Doctors from The University of Massachusetts, led by Miguel Sena-Esteves, conducted preclinical trials of genetic therapy for Tay—Sachs disease. Therapy consists in the delivery of genes encoding enzyme subunits to the brain of patients using a viral vector. In tests on mice, sheep and cats, the technique allowed to significantly slow down the progress of the disease, so scientists received the necessary approvals in order to conduct research on humans.
The first patients to receive experimental treatment were two children: a 2.5-year-old girl (patient 1) and a seven-month-old girl (patient 2). The second patient was injected with a vector into the subarachnoid space and into the thalamus, and the first only into the subarachnoid space, since the thalamus was severely affected. The treatment was well tolerated and did not cause side effects.
The content of hexozoaminidase A in the cerebrospinal fluid in children increased from 0.3 nanomol per milliliter to 0.5-0.6 nanomol per milliliter. After treatment, the girls' condition stabilized, although they retained neurological disorders. The first patient's seizures disappeared (she continues to take the same anticonvulsant medication as before the start of treatment). The younger girl had seizures after the introduction of the vector, she also began to take an anticonvulsant drug, which completely stops them. Given that usually epileptic seizures in children with Tay—Sachs disease are not treatable, and they die before the age of 4, and the first patient is in a stable condition at 4.5 years (two years after treatment), we can talk about the success of therapy.
In subsequent clinical trials, doctors are considering increasing the dose of the viral vector. They believe that the risk of complications is justified, since the disease is fatal.
Earlier we told how doctors with the help of lentiviral gene therapy launched the synthesis of adenosine deaminase in children with a deficiency of this enzyme in blood stem cells and cured congenital immunodeficiency caused by this defect.
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