On September 2, 2021, Patient Worthy attended a webinar from the SYNGAP Research Fund titled “Treatments in Development for Epilepsy Syndromes: Opportunities for SYNGAP1.” This program provided an overview of research into rare epilepsy syndromes such as SYNGAP1 and the approaches to treatment that are being investigated by scientists. The webinar was hosted by Ana Mingorance, Ph.D. The development of epilepsy therapies has been an active area of drug development in recent years.
About SYNGAP1 Intellectual Disability
SYNGAP1-related intellectual disability, often just called SYNGAP1 or SYNGAP1 syndrome, is a genetic disorder that impacts the central nervous system. As the name suggests, the disease is caused by a missense or loss of function variation on the SYNGAP1 gene, which codes for an essential protein for brain development. These variations usually appear randomly as opposed to being inherited from the parents. Symptoms of SYNGAP1 include epileptic seizures, gait instability, mild to severe intellectual disability, hypotonia, autism, and problems with sensory processing. Treatment is supportive and symptomatic and varies depending on the specific needs of the patient; common approaches include anti-seizure medications, mobility aids, a feeding tube, and physical therapy. There is no cure or disease-modifying treatments. Many patients have epilepsy that is resistant to most available medications. To learn more about SYNGAP1, click here.
Developing a Treatment
Dr. Mingorance says that over 25 medicines have been approved to treat epilepsy, with many of the new medications appearing in the last four decades. With that being said, these therapies do not all represent unique mechanisms of action. Mingorance classifies the available treatments into four different mechanisms. This means that there are actually significantly fewer options than it may first appear, and there are still a substantial number of patients that do not respond to them.
In the pharma industry, there has been a greater interest in developing treatments for rare epilepsy syndromes. Dr. Mingorance says that there are a number of approaches that could be useful for treating SYNGAP1.
Epidiolex, a CBD formulation, has been approved for use in certain rare epilepsies, and could also likely be effective in controlling the seizures found in SYNGAP1. Other approaches that could be used to develop a therapy for the disease include antisense oligonucleotides, which alter the expression of the gene associated with the disorder. Trials are currently underway for Dravet syndrome, another type of epilepsy syndrome.
SYNGAP1 could also be treated using gene therapy. This could be CRISPR-based or could use the AAV viral delivery system.
All of these options make it clear that SYNGAP1 can be treated effectively, but the drug makers simply haven’t made it a priority. The disease community will have to advocate hard to establish relationships with drug companies and scientists to fund research and drug development.
You can check out the full webinar here.