They are also called Angels; children with Angelman syndrome. Although the name sounds endearing, it is a very serious brain disorder. Children with Angelman have a developmental delay: they cannot speak, have difficulty walking and have seizures.
The cause of Angelman syndrome is in the genes, so a therapy that corrects the genetic flaw offers a possible treatment method. “Tackling genetic disorders in a genetic way is a wonderful opportunity. This way we can not only diagnose the abnormality, but also really do something about it,” says Ype Elgersma, professor of molecular neurobiology at the Department of Clinical Genetics. He leads research into genetic therapy for Angelman syndrome at Erasmus MC.
‘Vadergen’
Angelman patients have a mutation in the UBE3A gene that plays an important role in brain development. Every person has two copies of the UBE3A gene, one from the father and one from the mother. The mother’s gene is active and the father’s gene is turned off. This is where things go wrong in patients with Angelman syndrome: due to a mutation in the mother’s gene, there is no active UBE3A gene left.
“We hope to be able to switch on the dormant UBE3A gene of the father with genetic therapy,” says pediatric neurologist and researcher Marie-Claire de Wit. “To activate the gene, we use antisense oligonucleotides (‘ASOs’), short pieces of genetic material. We give these oligonucleotides through an epidural so that they can reach the brain. In the brain cells they put the UBE3A gene of the father and hopefully we can stimulate the brain development of Angelman patients again.”
Strikingly young
A team from Erasmus MC is investigating whether this approach works in a clinical study that started in 2021. It is the first time that genetic therapy has been studied in this way in patients with developmental disabilities. Elgersma and De Wit head the expertise center ENCORE (Hereditary Neuro-Cognitive Developmental Disorders Rotterdam Erasmus MC) where the research takes place. There is no shortage of knowledge about the Angelman syndrome in this center: they have the largest Angelman expertise center in the world.
A total of 60 Angelman patients are taking part in the study, in which a number of other hospitals are involved in addition to Erasmus MC. The participants are all between 1 and 12 years old, a remarkably young age for such a clinical study. Elgersma explains that this was a conscious choice: “Mouse studies show that the therapy can work especially well if you treat patients at a young age. The brain is still fully developing and there is still room to make progress.”
De Wit and Elgersma hope to be able to share the first results of the study next year. Elgersma is hopeful for the future: “The whole world is now watching us. If genetic therapy works for this group of patients, I still have a whole list of brain disorders for which we can also use it.”
By: National Care Guide