Ultragenyx, California, and GeneTx, Florida, two biopharmaceutical companies, in collaboration with each other, started a small clinical trial to study the safety of gene therapy for Angelman syndrome. This trial is put on hold as two of the participants temporarily lost their ability to walk.
Angelman syndrome is a rare autism-related genetic condition that occurs due to mutation or absence of a gene named UBE3A, affecting normal neural developments. Typically, people inherit two copies of the UBE3A gene, where the maternal copy is active in neurons and the paternal copy is inactive or silent. In Angelman syndrome, the maternal copy is absent or mutated. As a result, the brain cells do not express active UBE3A protein. Such mutation causes balance and motor problems, intellectual disability, seizures, and sleep disorders. GTX-102, the drug administered in the trial, comprises a snippet RNA called an antisense oligonucleotide involved in the activation of the paternal copy of UBE3A protein. Researchers believed that such activation would restore the protein imbalance and thereby help patients with Angelman syndrome. Three other companies, namely, Biogen, Roche, and Ionis are conducting similar research to treat the syndrome.
Positive and Negative Effects of the Therapy
The clinical trial consisted of 5 participantswith Angelman syndrome aged between 5 and 15. Scientists had planned to inject a dose of GTX-102 to individual candidates once a month over four months. The drug would be injected directly into a specific site in the lower back. Over the months, the doses given to the participants would increase. Initially, each participant would start with a varying dose, for instance, two of the participants would receive the lowest dose, while the others would receive higher doses. The researchers evaluated positive results within the few days of the first administration of the drug to the participants. The participants showed improvements in sleep, communication, and motor skills.
Elizabeth Berry-Kravis, professor of child neurology at Rush University Medical Center in Chicago, Illinois, reported that two of the participants complained about losing the ability to walk, while the other three participants showed some weakness. These side effects occurred as a result of the inflamed nerves where the drug was injected. The researchers thought that such inflammation occurred maybe because of the drug accumulation in the injected area. However, the inflammation was reported to have reduced on administering appropriate anti-inflammatory drugs, and the participants could walk again. They were also found to be more coordinated than they were before the study.
Moving forward, Ultragenyx chief executive officer, Emil Kakkis, stated that that the company has planned to optimize the dose such that the participants would show the positive traits without developing any weakness in their legs. The researchers would also establish a new drug administration method such that no drug accumulation would occur. Scott Stromatt, chief medical officer of GeneTx, stated that they will seek approval from the U.S. Food and Drug Administration, and hope to resume their study within the next two months.