NIH immune-based treatment study underwayPANDAS treatment study targets errant antibodies
Meanwhile, Swedo, Leckman, and Madeleine Cunningham of the University of Oklahoma, and colleagues, are collaborating on a new, multi-site placebo-controlled study, testing the effectiveness of intravenous immunoglobulin (IVIG) for reducing OCD symptoms in children with PANDAS.
Previous human and animal research suggested mechanisms by which strep-triggered antibodies mistakenly attack specific brain circuitry, resulting in obsessional thoughts and compulsive behaviors.
"Strep bacteria has evolved a kind of camouflage to evade detection by the immune system," Swedo explained. "It does this by displaying molecules on its cell wall that look nearly identical to molecules found in different tissues of the body, including the brain. Eventually, the immune system gets wise to this 'molecular mimicry,' recognizes strep as foreign, and produces antibodies against it; but because of the similarities, the antibodies sometimes react not only with the strep, but also with the mimicked molecules in the human host. Such cross-reactive 'anti-brain' antibodies can cause OCD, tics, and the other neuropsychiatric symptoms of PANDAS."
IVIG, a medication derived from normal antibodies, neutralizes such harmful antibodies, restoring normal immune function. It is used to treat other autoimmune illnesses and showed promise in a pilot study with PANDAS patients.
"We predict that IVIG will have striking benefits for OCD and other psychiatric symptoms, and will prove most effective for children who show high levels of anti-brain antibodies when they enter the study," said Swedo.
Prospective study participants are first screened by phone by investigators at the NIH or the Yale Child Study Center. Those who meet eligibility requirements are then randomized to receive either active IVIG or a placebo procedure during a brief inpatient stay at the NIH Clinical Center. The researchers remain blind to which children received the active medication; after 6 weeks of placebo control, they give any children whose symptoms fail to improve the option to receive open-label active treatment.
In addition to assaying for antibodies that attack brain cells, the researchers usemagnetic resonance imaging to see if the treatment reduces inflammation in an area of the brain known as the basal ganglia, which is thought to be the target of the errant antibodies. They also analyze levels of immune system chemical messengers (cytokines) in cerebrospinal fluid and blood - with an eye to identifying biomarkers of disease activity and potential predictors of treatment response.
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