Thought Process and Promise Behind Targeting mTOR Pathway for Pediatric Epileptic Encephalopathies: Ghayda Mirzaa, MD
The principal investigator at Seattle Children’s Research Institute provided commentary on the therapeutic potential and hypothesis behind targeting mTOR pathway hyperactivation using pharmacological inhibitors. [WATCH TIME: 3 minutes]
WATCH TIME: 3 minutes
"The mTOR pathway holds enormous clinical relevance—what was once thought to be untreatable in severe neurological conditions like DEEs is now showing real promise through targeted mTOR inhibition, offering potential hope for children and families impacted by these devastating disorders."
Epilepsy, one of the most common neurological disorders, is characterized by recurrent spontaneous seizures and is often associated with comorbidities, including cognitive, psychiatric, and other neurobiological consequences, which can significantly affect quality of life. Despite the advancements in antiseizure medications, approximately one third of individuals with epilepsy have medically refractory epilepsy and do not respond to available treatments. This raises the need for pharmacologic or genetic therapies that target the molecular mechanism of early onset progressive neurologic disorders, like epilepsy.
At the 2024 American Neurological Association (ANA) Annual Meeting, held September 14-17 in Orlando, Florida, several clinicians presented in a session on state of the art treatments for epileptic encephalopathies, neuromuscular, and mitochondrial disorders. One presentation, given by co-chair Ghayda Mirzaa, MD, focused on the potential of targeting mTOR pathway as a treatment approach for developmental encephalopathies and mTOR-related epilepsy. Signaling via mTOR has been implicated in several epileptogenic processes, including synaptic plasticity mechanisms and changes in ion channel expression following seizures.
Mirzaa, a pediatrician and research who has dedicated her career to helping children and families with developmental brain disorders, sat down during the meeting to discuss the promise behind this pathway. She stressed that this pathway is crucial at both the cellular and clinical levels, with mutations in various genes within the pathway linked to a range of neurological phenotypes, including epilepsy, autism, and intellectual disabilities. Mirzaa, who 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, provided context on why this approach has gained more attention, which includes success seen in the oncology field.
