[JCI Insight] Angel syndrome is expected to improve!

This article is original by Translational Medicine Network.
Please indicate the source for reprinting.
Author: Ashley Guide: Angel Syndrome is a neurodevelopmental disorder caused by genetic abnormalities, characterized by poor muscle control and balance, difficult-to-treat epilepsy and intelligence Disability
.

There is no specific treatment for this disease, but recent studies have shown that restoring the function of the UBE3A gene in neurons is expected to significantly improve the quality of life of patients with Angel Syndrome! Scientists from the University of North Carolina (UNC) School of Medicine published a report in "JCI Insight" entitled "Dual-isoform hUBE3A gene transfer improves behavioral and seizure outcomes in Angelman syndrome model mice" Early testing of gene therapy strategies
.

Angel syndrome is a neurodevelopmental disorder characterized by poor muscle control and balance, difficult-to-treat epilepsy, and intellectual disability
.

Approximately one in every 20,000 children suffers from Angel Syndrome, and more than 15,000 people in the United States alone suffer from this disease
.

There is currently no specific treatment, but Dr.
Ben Philpot, Distinguished Professor of Cell Biology and Physiology at Kenan UNC School of Medicine and Associate Director of the UNC Neuroscience Center, previously suggested that the best way to treat diseases is to restore UBE3A gene function neurons.
People with syndrome have disappeared from their brains
.

The genes of Angel syndrome are more complicated than classic single-gene diseases such as cystic fibrosis and sickle cell anemia
.

Humans have inherited a maternal and paternal copy of most genes
.

Angel syndrome occurs in children whose maternal UBE3A gene is mutated or deleted in some way
.

For reasons that are not fully understood, mature neurons usually express only the maternal copy of UBE3A; the paternal copy is effectively silenced
.

Therefore, when the maternal copy is lost, the function of the gene in the neuron is lost
.

Because the protein encoded by UBE3A can help regulate the levels of other important proteins, its absence can severely disrupt brain development
.

What’s more complicated is that neurons express two different variants or "isomers" of UBE3A, their lengths are slightly different, one is short, one is long, and the ratio is about three short and one Kind of long
.

Philpot's team was able to create a version of UBE3A that, when expressed by neurons, can produce short and long UBE3A proteins in close to normal ratios
.

The scientists inserted the therapeutic UBE3A gene into a virus-derived vector, designed to be reliably delivered to neurons
.

They injected a solution of this vector into the brain ventricles of newborn angel syndrome model mice, which lacked a copy of the mother mouse UBE3A gene
.

Like humans with Angel Syndrome, these mice cannot express the UBE3A protein in their neurons, and develop motor deficits, epilepsy, and other neurological symptoms in the first few months of life
.

Philpot and his colleagues confirmed that the UBE3A carried by the vector became active in neurons in the brain of the angel syndrome model mouse within a few days after the injection, and its levels were similar to normal genes
.

This treatment restored the mice's motor skills learning and basic digging, burrowing and nesting behaviors
.

Untreated mice showed common angel syndrome injuries
.

Compared with untreated mice, the treated mice did not become as sensitive to experimentally induced seizures and, importantly, did not suffer any significant side effects
.

The first author of the study, Dr.
Matt Judson (a research assistant in Philpot’s lab who conducted most of the trials) said: “This is a proof-of-concept study, but if these early results are translated into the clinic, they will represent Significant improvement in the quality of life of patients with Angel Syndrome
.

" The researchers plan to further develop their strategy, first by conducting more experiments in mice and monkeys to optimize dosage and delivery methods, and finally, until promising safety results are obtained.
Then conduct human clinical trials
.

If this therapy is feasible, researchers expect it may benefit people of any age, but it may be a different benefit
.

Philpot said: "The range from birth to 4 years old may be ideal, but we believe that as long as we can restore the function of this gene in the brain, we are likely to see some improvement
.

" Reference: https:// medicalxpress.
com/news/2021-10-gene-therapy-early-angelman-syndrome.
html Note: This article aims to introduce the progress of medical research and cannot be used as a reference for treatment options
.

If you need health guidance, please go to a regular hospital
.

The 3rd Shanghai International Cancer Conference [Live] Opportunities and Challenges for Standardization of TMB Testing Hot Articles New Crown Epidemic [Cell Sub-Journal] Under the COVID-19 cover, are the stem cell therapies that are competing to develop really effective? There may be a lack of certain clinical trials and scientific proofs of tumor research [Cell Sub-Journal] For the first time to draw a molecular map of small cell lung cancer, the use of single-cell RNA sequencing to reveal the behind-the-scenes promotion of tumor metastasis-an unusual cell type, the new crown epidemic [ Science blockbuster] WHO has established a new team including Yang Yungui of the Chinese Academy of Sciences to restart research on the origin of the pandemic that may have come from laboratory leaks! Medical progress [Science hot discussion] Only 17 women in 115 years! Why do men often sweep the Nobel Prize and so few women winners? Intelligent diagnosis [Research] "Artificial Intelligence + Biomedicine" applied to liver cancer with a high mortality rate is expected to completely change the diagnosis and treatment of cancer in the future! Disease prevention [Science] WHO launched a new "global roadmap" to develop a low-cost five-in-one vaccine, which is expected to eliminate bacterial meningitis epidemic intestinal flora by 2030 [Nature Sub-Journal] Intestinal Warfare: Demystifying the Human Intestine Interview with an expert on how the Dao microbiota resists cholera bacteria "Zhuan" Interview with Professor Xu Chenming from the Obstetrics and Gynecology Hospital of Fudan University: Non-invasive prenatal screening has entered the era of clinical application of monogenic diseases.
Medical progress [Nature hot discussion] Why the 2021 Nobel Prize is not Awarded the COVID-19 vaccine that saves countless lives?