Key Challenges and Future Directions of Targeting mTOR for Epileptic Disorders: Ghayda Mirzaa, MD
The principal investigator at Seattle Children’s Research Institute described some of the ongoing questions that remain with developing therapeutics that target mTOR signaling pathway in pediatric epilepsy conditions. [WATCH TIME: 3 minutes]
WATCH TIME: 3 minutes
"One of the main important questions we have is, can we actually use mTOR inhibitors across, regardless of the gene and regardless of the mutation? Can we adapt a pathway-based approach to this? I think that's a really important practical question, because that could allow us to tackle things at a pathway level, just like is being done in cancer."
There are 50 million newly diagnosed patients with epilepsy worldwide each year. As the first-line treatment for epilepsy, drug therapy improves the excitatory/inhibitory imbalance of the brain after seizures by targeting ion channels or neuronal transmission. Despite the advances in antiseizure medications and surgical approaches, there are still several patients who struggle to control their seizures, including those with developmental epileptic encephalopathies.
The serine-threonine kinase mTOR, is a key point in the important eukaryotic signaling network that coordinates cell growth and environmental conditions and acts as a core regulator for many other psychological factors. In the nervous system, mTOR plays an important role in synaptic plasticity, brain development, and neuronal survival. Previous research has also shown that mTOR signaling is involved in highly epileptogenic diseases, including tuberous sclerosis complex, and is a reasonable target for antiepileptic intervention.1
At the 2024 American Neurological Association (ANA) Annual Meeting, held September 14-17 in Orlando, Florida, Ghayda Mirzaa, MD, gave a presentation on the hypothesis behind targeting mTOR for developmental encephalopathies and mTOR-related epilepsy. During the meeting, she sat down to discuss the challenges and future directions in targeting mTOR pathway for treating epilepsy, particularly in pediatric patients. Mirzaa, serves as an associate professor of pediatrics and medical genetics at the University of Washington School of Medicine and principal investigator at the Seattle Children’s Research Institute, highlighted the diagnostic challenges posted by mosaic genetic mutations, which are often brain-specific and difficult to detect non-invasively. Furthermore, on the therapeutic side, she emphasized the potential for a pathway-based approach to using mTOR inhibitors, regardless of the specific genetic mutation involved, which may open new avenues for treating these disorders more effectively.
