[ad_1]
Guido Mieth / Getty Images
The United States Food and Drug Administration (FDA) has paved the way for a clinical trial of gene therapy for Angelman syndrome to resume. FDA suspended the trial last November after the children who received the treatment temporarily lost the ability to walk.
Angelman syndrome is a genetic disease caused by the absence or mutations in the maternal copy of the gene UBE3A; it is often accompanied by autism. Gene therapy, called GTX-102, aims to activate the paternal copy of the gene, which is usually silenced.
Biopharmaceutical company Ultragenyx in Novato, Calif., is conducting the trial in conjunction with a Florida-based biotech startup GeneTx. In May and June, regulators in Canada and the UK, respectively, gave companies the green light to begin testing the drug.
“It’s nice to see that we are able to restart again in the United States”, says Timothy yu, associate professor of pediatrics at Harvard University. Yu is not involved in the trial but says he has advised companies and hopes to start a trial site at Boston Children’s Hospital.
In February of last year, five children with Angelman syndrome began receiving gradually increasing doses of the injection therapy in the lower back. But by July, all five had leg weakness, which was severe enough in two children to prevent independent walking. The researchers stopped giving doses at that time, says Scott stromatt, Chief Medical Officer of GeneTx. The FDA officially suspended the trial in November.
All of the children made a full recovery, Stromatt says, and researchers attribute the problems to inflammation at the injection site caused by higher doses of the drug. They continue to test children’s blood to confirm this theory. In the meantime, eight new children with Angelman syndrome have been recruited to take lower doses.
“We will be leaving very soon,” says Stromatt. “The most important thing is safety and to do it with care.”
Dosage adjustment:
In the new trial, four children aged 4 to 8 who were not previously treated with GTX-102 will receive four monthly doses of 2 milligrams of the drug. Four more children will not receive the drug. Both groups will be assessed at the start of the trial and after 128 days, at which time the control group can also begin treatment.
In a second phase, the eight children – if their families wish – will continue to be treated every three months.
In the previous trial, the GTX-102 dosage started at 3.3 milligrams and increased to 20 and in some cases 36 milligrams, when the side effects started. (Trials in the UK and Canada use 3.3 milligrams in young children and 5 milligrams in children ages 8 to 17.) Researchers are also monitoring proteins in the blood and cerebrospinal fluid of children. as an added safety measure, says Stromatt.
Children from the previous trial seemed to show improvements communication, motor skills and to sleep before he was arrested, and parents continue to report progress. Children May Respond Slower To Lower Doses In New Trial, Stromatt Says
The reboot is “promising,” says Marc Zylka, a professor of cell biology and physiology at the University of North Carolina at Chapel Hill, who is not involved in the trials. Lower doses are likely to prevent serious side effects, he says, and although the groups are too small to rigorously assess the drug’s effectiveness, any improvement would suggest that these types of gene therapies are a promising route to treat. neurological development disorders.
“I can’t wait to see what they find,” Zylka says.
If further trials confirm the drug is effective, it would suggest that the brain retains the ability to respond to treatment during childhood, Yu says.
“The existence of an open therapeutic window is what the first trial results really seem to suggest, and that’s why everyone in the field is watching this so closely,” he says. “This has the prospect of being a basic truth common to many of these neurodevelopmental disorders, and that’s what’s exciting about it.”
Quote this article: https://doi.org/10.53053/SOQL5387
[ad_2]
Source link