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The excitement of bringing home a child is unlike any other experience. These parents envision their child’s future to be full of love, happiness, independence, and growth. However, when a child is diagnosed with Angelman Syndrome, the life that the parents originally envisioned suddenly changes dramatically, and their excitement is replaced with fear of the unknown. Many developmental disabilities are surrounded by unknowns due to the lack of research within the healthcare field. Angelman Syndrome is a neuro-genetic condition that first presents with constant happiness (Derewicz 2021). Because hyperactivity, smiling, and laughter is common amongst all young children, parents do not suspect that anything is wrong. Angelman Syndrome is only diagnosed when the child begins to have developmental delays, intellectual disability, regular seizures, and problems with movement. Around 1 in every 12 to 20 thousand people are diagnosed with AS (Angelman Syndrome 2020). Genetically, the gene UBE3A on chromosome 15 is either muted or deleted (Derewicz 2021). While there are no active treatment options for AS, individuals receive lifelong palliative care from occupational therapists, neurologists, and most importantly, their caregivers.
Recently medical researchers Ben Philpot, Ph.D., and Mathew Judson, Ph.D., at the University of North Carolina Medical Center have led a diverse group of researchers from around the world in order to create a treatment option for Angelman Syndrome (Derewicz 2021). Their clinical research trial on mice with AS has had some promising results for the future. Past research has indicated that the inactivity of maternal gene UBE3A on chromosome 15 is the main cause of AS, and phenotypic symptoms of AS. The process of AAV transfers has been used on many different types of gene therapy trials over the last decade (Judson et al. 2021). The RNA virus being introduced is not fully developed, so it is not strong enough to actually harm the body. In actuality, this synthetic virus’s purpose is to provide the brain cells with the correct genetic information that they are missing due to the mutation or deletion of chromosome 15.
In order to test their hypothesis, the researchers used three different groups of mice with AS and gave them a different type of treatment plan. Groups 1 and 2 were both treated with the same synthetic gene, however, the ratio of short to long RNA virus samples were different. The control group (group 3) was given a placebo treatment which did not contain any strand of the synthetic gene to compare the other two groups to at the end of the study. After the mice underwent treatment, they were tested on their ability to carry out certain tasks. The mice were observed on nesting, marble burying, rotarod, fear conditioning, and open field navigation. Each of these tasks were symbolic of the natural habits of normal mice. The experiment was done as a blind study, so the researchers did not know which group they were observing throughout the experiment. This was done to prevent observer bias. Because epilepsy is a major symptom of AS, all the mice were periodically checked for seizure activity. At the end of the experiment, the results indicated that the mice with the placebo treatment had clear difficulties in carrying out the tasks, and they had abnormal seizure activity. This was expected, as the placebo group was representative of the limitations AS gives individuals. The results also showed some differences between groups one and two. In group two there was a slightly larger improvement in behavioral and motor learning skills compared to the mice in group one; however, in group one there was evidence that showed improvement in both seizure activity as well as an increase in motor and behavioral traits (Judson et al. 2021). Throughout the experiment, the researchers outlined some of the limitations that could be resolved in future experiments. For example, the researchers admitted that they should have considered that mice experience behavioral and environmental stimulation. They also took into account the time of treatment given to the mice compared to when the time of treatment would be possible to give a human with AS. The mice were given an ICV neonatal injection 2-3 weeks before birth, however, because AS is only diagnosed in humans in infancy or early childhood this would pose some questions as to whether the treatment option would still have the same effects.
Overall, the results of the experiment show promise for the synthetic gene, and its effectiveness on reactivating the gene UBE3A. However, the key to starting a clinical trial on humans is finding the absolute best ratio of short to long strands of the RNA virus that is behind the gene therapy. While it is quite evident that this treatment option is quite a ways away from being FDA approved, the study has taken a monumental step in finding a treatment that could be implemented in the future. A majority of clinical research is focused on finding cures and treatment options for terminal illnesses, like cancer or MS, and developmental disabilities are often overlooked. However, countless parents and families hope for any information that can help answer the unknowns of disorders like Angelman Syndrome. Being that Angelman syndrome has common genetic links with Autism (Angelman Syndrome 2020), and finding a treatment plan or cure could pave the way for finding cures for other genetic disorders like autism. There is such a large community of people in the developmental disability community that could benefit from finding a gene therapy treatment option. Only the caregivers of individuals with Angelman Syndrome know how hard life can be for them. The bright smiles of these individuals hide the hardships they face on a day-to-day basis but studies like this one can potentially shine a light on treatments for these hardships, which in turn would improve health outcomes and the quality of life for countless individuals.
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Featured Image Source:
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