Gene Therapy and Gene-Editing Techniques Might Be the Answer to Angelman Syndrome in Children

Infants born with the aberrated copy of UBE3A gene, inherited from mother, develop Angelman syndrome which is a severe neurodevelopmental disorder with no cure available and have limited treatments.

As of now, researchers at the University of North Carolina Health Care, for the first time showed that techniques like gene editing and gene therapy can be used to restore the UBE3A mutation in human neuron cells to treat the neurodevelopmental deficits in mice model of Angelman syndrome, results published in Nature, setting a benchmark to intervene long-lasting treatment or to develop a cure for this debilitating disease.

Angelman syndrome (AS) is a severe neurodevelopmental disorder which is caused by a genetic mutation or deletion of the one copy of UBE3A gene that is inherited from mother. This UBE3A gene makes a protein “ubiquitin protein ligase E3A (UBE3A) enzyme”. The other copy of this gene inherited from father is usually silenced or unfunctional and the other copy inherited from mother is active and functional.

Therefore, loss of mother copy of gene results in a complete absence of the UBE3A enzyme in most areas of the brain. This predispose to severe deficits because the HBE3A enzyme targets proteins for degradation, a critical process that maintains normal functioning of brain cells. As a result of mutation, functionality of brain cells is compromised, resulting in a brain disorder called the Angelman syndrome characterized by the severe intellectual and developmental disabilities, seizures, and problems with speech, balance, movement, and sleep.

Source: Knowing Neurons

In the study, the UNC team used the “adeno-associated virus (AAV) gene therapy” techniques to deliver the Cas9 protein to embryonic mice brain who had the syndrome. Since the UBE3A gene is crucial for the normal physiology and development of brain, researchers showed that the early treatment of mice at the embryonic and postnatal stage can restore the adverse physical and behavioral outcomes of the syndrome.

It was remarkable to demonstrate that a single neonatal injection of AAV gene therapy considerably expresses the gene copy of father to cover the loss caused by the lost gene copy of mother for at least 17 months. Results suggest that this reported effect can likely be permanent and prevent the complications. It was also reported that this effect was effective in human neuron cells as well, giving hope to treat the human.

Study therefore implicates that no other treatments are currently available that are being pursued to treat the Angelman syndrome. Moreover, no other treatments are available to address the symptoms and limited treatments are available. Scientist are confident that it eventually help in recognizing the advantages of detecting the genetic mutation at the prenatal stage to prevent progression of the aggressive Angelman syndrome.

“Since we learned we could reduce the severity of Angelman syndrome in mice, we are now focused on refining our approach in ways that will be suitable for use in humans,” said, Hanqian Mao, PhD.

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