Gene therapy is promising early as a treatment for Angelman syndrome

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UNC School of Medicine Scientists Reported to Journal JCI Insight Encourage early testing of gene therapy strategies for neurodevelopmental disorders characterized by Angelman syndrome, inadequate muscle control and balance, difficult-to-treat epilepsy, and intellectual disability.

Angelman syndrome Approximately 1 in 20,000 children are affected, and more than 15,000 are thought to be in this condition in the United States alone.There is no specific cure, but scientists led by Dr. Ben Philpot, Kennan, Professor of Cell Biology and Physiology at UNC School of Medicine, and Deputy Director of the UNC Center for Neural Science, have previously been the best to treat disorders. Proposed method will restore functionality UBE3A Genes of neurons that are lost in the brains of people with Angelman syndrome.

The genetics of Angelman syndrome are more complex than classic monogenic disorders such as cystic fibrosis and sickle cell anemia. Humans inherit one maternal and one paternal copy of most genes.Angelman syndrome occurs in children whose mother is the mother UBE3A The copy has been modified or deleted for some reason. For reasons that are not completely clear, mature neurons usually express only a maternal copy. UBE3AThe paternal copy is effectively silenced. Therefore, when the maternal copy is lost, the function of the gene ceases to exist in the neuron.because UBE3A It encodes a protein that helps regulate the levels of other important proteins, and its lack is terribly confusing. Brain development..

Increasing complexity, neurons represent two different variants or “isoforms” UBE3A The lengths of the short and long formats are slightly different, with a ratio of about 3 short formats for each long format.

Philpot’s team UBE3A When expressed by neurons, it produces short and long forms of UBE3A protein in near normal proportions.Scientists have inserted their remedies UBE3A A virus-derived carrier designed for reliable delivery to neurons, or a gene into a “vector”. They injected a solution of this vector into a hollow space called the ventricle in the brain of a neonatal Angelman syndrome model mouse that lacked a maternal copy of the mouse. Ube3a gene. Like humans with Angelman syndrome, these mice are unable to express the UBE3A protein in neurons and develop movement disorders, seizures, and other neurological symptoms in the first month of life.

Philpot and colleagues confirm that it is vector-mediated UBE3A Became active in Neuron Just days after injection, at levels similar to normal genes, the entire brain of Angelman model mice. This treatment restored motor skills learning and the essential behavior of mice to dig, dig, and nest. Untreated mice developed normal Angelman-like disorders. Treated mice were also less sensitive to experimentally induced seizures than their untreated counterparts, and, importantly, did not suffer any obvious negative side effects.

“This was a proof-of-concept study, but if these early results were reflected in the clinic, it would mean a significant improvement in the quality of life for individuals with Angelman syndrome,” said the lead author of the study. One Dr. Matt Judson said. , A Philpot Lab researcher who conducted most of the experiments.

Researchers initially conducted more studies in mice and monkeys to optimize doses and delivery methods, and eventually conducted human clinical trials until promising safety results were obtained. , We are planning to further develop our strategy. If such a treatment is available, researchers hope it may benefit individuals of all ages, but there are probably varying benefits.

“The range from birth to 4 years is probably ideal, but we believe that whenever we can restore the function of this gene in the brain, we’re likely to see some improvement,” Philpot said. I am.

Does Gene Therapy Help Children with Angelman Syndrome Overcome Seizures?

For more information:
Matthew C. Judson et al, dual isoform hUBE3A gene transfer improves behavior and seizure outcomes in Angelman syndrome model mice. JCI Insight (2021). DOI: 10.1172 / jci.insight.144712

Quote: Angelman Syndrome Treatment (October 22, 2021) was obtained from on October 22, 2021. , Gene therapy shows early prospects

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Gene therapy is promising early as a treatment for Angelman syndrome

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