Children born with a rare, genetic brain disorder that causes severe atrophy and often leads to death within three years, are still alive 7 to 10 years after being treated with an experimental gene therapy, a study showed.
The findings, published today in the journal Science Translational Medicine, described the procedure of inserting a virus containing healthy genes into the children’s brains through holes drilled into their skulls. The 13 children, the youngest of whom was 3 months old and diagnosed with the disorder while in the womb, were treated at the Cell and Gene Therapy Center at the University of Medicine and Dentistry of New Jersey in Stratford.
The children are among only about 600 people in the world with the disorder, called Canavan disease, a nerve-cell destroying condition marked by brain atrophy, seizures, vision loss, physical disability and ultimately death. There is no treatment or cure.
“We were able to change a terminal diagnosis in these patients into a non-fatal diagnosis,” study author Paola Leone, an associate professor of cell biology at the University of Medicine and Dentistry New Jersey, said in a telephone interview.
The study, which began in 2001, was the first approved by U.S. regulators using an adeno-associated virus, a type of virus used in gene therapy because of its benign effects on humans.
Today’s oldest patient in the clinical trial is 18 years old. The patient “has major cognitive abnormalities, but she’s not in a vegetative state,” Leone said, and indicates “yes” by blinking and “no” by opening her mouth.
Canavan disease is caused by recessive mutations. When two of these occur, people can’t make an enzyme used to break down a compound called NAA in nerve cells in the brain. The buildup in the brain, along with unusual patterns of the insulation called myelin that lines nerve cells, are characteristic of the illness.
Scientists aren’t sure whether the buildup of NAA is what causes the brain damage, or whether the enzyme has another role they haven’t yet discovered, Leone said. As the myelin degenerates, the child has difficulty moving, has seizures and goes blind.
In the study, doctors inserted healthy genes into the patients’ brain cells, allowing them to produce the enzyme. The first patients treated in the study were the oldest, the researchers said.
The younger the patient was at the time of the procedure, the better the response seemed to be, according to the study. The three oldest patients didn’t become more alert, but their awareness of the world around them didn’t deteriorate. The 10 younger patients all demonstrated improved alertness.
After treatment, 11 patients had decreases in the numbers of seizures they suffered; two had no seizures before or after treatment. The major adverse event was an abscess in the burr hole in one patient’s skull following the surgery.
The treatment costs $100,000 for the first two years, said Leone. Her group is looking for a company or philanthropist who can finance clinical trials for the third and final stage of testing generally required by the U.S. Food and Drug Administration.