Experimental Treatments for Angelman Syndrome

Angelman syndrome (AS) is a genetic disorder that can delay development and cause neurological problems and seizures. Currently, there is no cure for AS. The available medication can only control seizures and should be accompanied by physical, communicative, and behavioral therapy to manage other symptoms.

Research into specific genes causing AS is ongoing. This could lead to the development of new therapies designed to target these genes. Examples of ongoing research are described below.

Gene therapy

Gene therapy involves supplying the cells of a patient with a functional copy of a gene that is missing or mutated, therefore treating the underlying cause of the disease. In AS, this is the UBE3A gene.

Everyone has two copies of every gene, one inherited from the mother and one from the father. Normally, only the maternal copy of the UBE3A gene is active, while the paternal copy is “silenced”. Therefore, if there is a deletion or a mutation in the UBE3A gene inherited from the mother, the child develops AS.

Agilis Biotherapeutics is currently developing a therapy called AGIL-AS, that aims to deliver a functional copy of the UBE3A gene to the brain and spinal cord in an attempt to treat AS.  This would be done using a modified virus called an adeno-associated virus, or AAV as a vector. A vector is a vehicle used to carry a gene inside cells.

Studies in mouse models of AS have demonstrated that delivering the UBE3A gene directly to the nerve cells using an AAV vector can improve cognitive problems, such as learning. These results are published in the scientific journal PLoS One.

AGIL-AS was granted orphan drug designation by the U.S. Food and Drug Administration (FDA) in November 2015 and by the European Commission (EC) in May 2016.

Topoisomerase inhibitors

Another mechanism being investigated to restore UBE3A gene expression is by activating the paternal copy of the gene. A research group at the University of North Carolina, School of Medicine screened drugs approved by the FDA for other conditions as potential candidates that could reactivate the UBE3A gene. With this approach, they identified a drug used in cancer treatment called topoisomerase 1 inhibitor or topotecan, which successfully reactivated the dormant UBE3A gene in a mouse model of AS. These results were published in the prestigious scientific journal Nature. No clinical trials have been carried out yet to determine the safety and efficacy of topotecan in AS patients.


Scientists have shown that the antibiotic minocycline has an effect on the nervous system, and is beneficial in patients with various neurological disorders including Alzheimer’s disease, Parkinson’s disease, and fragile X syndrome.

Following this, a team of researchers at the University of Florida carried out a pilot trial (NCT01531582) to assess whether minocycline could improve the cognitive and behavioral symptoms of AS. The results, published in the scientific journal BMC Neurology, suggested that minocycline was well tolerated in AS patients, ages 4 to 12 and appeared to improve communication, motor control, and understanding. Further long-term trials are still needed to fully assess the safety and potential benefits of minocycline in AS.

Note: Angelman Syndrome News is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.