GABA-B receptor autoimmunity resulting in seizures and memory deficits

Eric Lancaster, M.D., Ph.D.

University of Pennsylvania

Funded in June, 2010: $200000 for 3 years


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Inserting patients’ antibodies into an animal model creates method to test therapies for a brain disease

Investigators will take antibodies from patients with an autoimmune form of limbic encephalitis and seizures, to explore how immune system antibodies produce this brain disease and how the disease can be treated in patients.

Some forms of encephalitis—brain inflammation that is usually caused by a viral infection—have recently been found to be produced instead by immune system antibodies that mistakenly attack brain cells. Patients with limbic encephalitis experience sudden changes in memory and cognition, and develop seizures. The investigators discovered that in some of these patients, the disease is associated with antibodies that attack molecules on certain brain cells that receive the neurotransmitter “GABA-B” to communicate with one another. Now they use the patients’ antibodies to create an animal model of the disease to better understand the disease process and test therapies to treat it.

First, they will study the actions of patients’ “autoantibodies” (from blood samples) on animal brain tissues in the laboratory and determine how the antibodies disrupt GABA receptors.   They will see whether antibodies: 1) block the receptor from activating; 2) remove the receptors from the nerve cell; or 3) kill the neurons that have this receptor. Based on their findings, they will develop an animal model of the disease and monitor how brain inflammation and seizures occur in the living brain.

Significance: By taking patients’ antibodies and creating an animal model of this autoimmune disease, the investigators will develop a new way to test therapies to treat it in humans.