Microbiology-Immunology Department: Dan Xu, PhD

The Microbiology-Immunology Department Seminar Series

"Immune Mechanisms of Intractable Pediatric Epilepsy and Development of Novel Therapies"

Topic:

Anticonvulsants are the standard treatment for epilepsy, but only control the symptoms without adressing the mechanisms of the disease. About 1/3 of patients develop drug-resistant epilepsies and only some are candidates for resective surgery as a final attempt to reduce seizure occurrence. Recently, we have pioneered the characterization of inflammatory cell infiltrates in surgically removed fresh brain samples in a search for novel therapies that may target the cause of epilepsy. Our data strongly indicate a role for immune cell activation in the epileptic brain irrespective of the particular etiology of epilepsy. We discovered significant brain infiltration of functionally activated lymphocytes in both epileptic patients and experimental animals. Additionally, steroids that are known for their anti-inflammatory properties have shown efficacy in a number of types of drug-resistant epilepsy. However, the profound immunosuppressive and other severe side effects of chronic steroid use have prevented widespread prescription of these drugs to otherwise treatable patients. We therefore use mouse models to design novel immunomodulatory therapies utilizing biodegradable nanoparticles formulated from the FDA-approved biopolymer poly(lactide-coglycolide) (PLG) to treat seizure .Our approaches that target inflammation and restrict brain infiltration by inflammatory leukocyte subsets in the absence of the complicating effects of steroids are highly novel and may be a major step forward for the translation of novel treatments for the root cause of epilepsy.​

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