Angelman Syndrome (AS)
Angelman syndrome (AS) is a neurogenetic disorder that affects the development of the nervous system and causes severe developmental delays. Our company's extensive experience in AS research allows us to provide you with customized services as well as comprehensive assistance that can help you move from AS therapy development to therapy commercialization.
Overview of Angelman Syndrome (AS)
Angelman syndrome (AS) is a rare disease with an estimated global prevalence of 1 in 10,000 to 1 in 20,000. The disorder is characterized by developmental delays, intellectual disability, and distinctive behavioral traits. The pathogenesis of AS is mainly attributed to an imprinting defect in the 15q11-q13 region of the chromosome. This defect leads to the loss of function of the UBE3A gene, which encodes for the ubiquitin protein ligase E3A.
- The 15q11-q13 region of the chromosome is subject to genomic imprinting, a process in which certain genes are expressed from only one parent's copy of the chromosome. In the case of AS, the UBE3A gene is normally expressed from the maternal allele, while the paternal allele is silenced. However, due to an imprinting defect, the paternal allele fails to be silenced, resulting in the absence of functional UBE3A protein in the brain.
- The UBE3A gene encodes for a protein called ubiquitin protein ligase E3A. This protein plays a crucial role in targeting proteins for degradation by the ubiquitin-proteasome system. In the absence of functional UBE3A protein, there is a disruption in protein degradation pathways, leading to abnormal neuronal function and synaptic plasticity. This disruption ultimately contributes to the cognitive and neurological symptoms observed in individuals with AS.
Fig.1 AS is caused by four different molecular mechanisms. (Maranga, Carina, et al., 2020)Diagnostics Development of AS
Genetic testing plays a pivotal role in confirming the diagnosis of AS. Blood samples are collected for analysis, and various genetic tests are performed.
- DNA methylation analysis: DNA methylation analysis can identify approximately 80% of individuals with Angelman Syndrome. It can detect abnormalities in the 15q11.2-q13 region, including 5- to 7-Mb deletion, UPD, or an imprinting defect.
- Single-gene testing: The comprehensive sequencing analysis of the UBE3A gene can detect small intragenic deletions/insertions, missense, nonsense, and splice site variants.
- Multigene panels: The multigene panels, including UBE3A and other relevant genes, are designed to identify the genetic cause of Angelman Syndrome while minimizing the identification of variants of uncertain significance and non-relevant pathogenic variants.
Therapeutics Development of AS
Currently, there is no cure for Angelman syndrome. However, therapeutic developments are being actively pursued to alleviate the symptoms and improve the quality of life for individuals with AS.
One area of focus is the development of pharmaceutical interventions. Research has identified potential drug targets, such as the enhancement of UBE3A expression or the modulation of related pathways involved in neuronal function. Some common therapy approaches include:
| Anti-epileptic medication | Drugs like Carbidopa and Levodopa have shown potential in managing symptoms such as seizures associated with AS. |
| Physiotherapy | Physiotherapy is beneficial for improving posture, balance, and mobility. |
| Communication therapy | Non-verbal communication techniques, such as sign language and visual aids, can help individuals with limited speech develop effective communication skills. |
| Behavioral therapy | Behavioral therapy may be recommended to manage challenging behaviors associated with AS. |
Our Services
As a leading company in the field of biological research and CRO services, our company is committed to providing diagnostic development services to develop rapid point-of-care diagnostic tests for AS and achieve the goal of accurate diagnosis. We provide state-of-the-art omics analysis services, utilizing advanced techniques to identify genetic abnormalities associated with AS.
Platforms of AS Therapy Development
We understand the importance of reliable animal models in the study of AS. We offer a comprehensive range of animal models for AS research. Our animal models have demonstrated key neuropathological features of AS, providing valuable tools for studying the underlying mechanisms and potential therapeutics for this disorder. We also provide different species to support the safety evaluation and pharmacokinetic analysis of AS drugs and therapies.
Animal Models of AS
If you are interested in our services, please feel free to contact us for more details and quotation information of related services.
Reference
- Maranga, Carina, et al. "Angelman syndrome: a journey through the brain." The FEBS Journal 287.11 (2020): 2154-2175.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.