New biomarker test helps detect autoimmune-induced neuropsychiatric disorders

A research team from the University of Oklahoma Health Sciences Center, led by Madeleine Cunningham, Ph.D., in conjunction with the National Institute of Mental Health (NIMH), has developed the first-of-its-kind biomarker test to help detect autoimmune-induced neuropsychiatric disorders.

The Cunningham Panel™ assists clinicians in identifying whether certain neuropsychiatric conditions, including obsessive compulsive disorders, tics, mood disorders and behaviors associated with autism spectrum disorder (ASD), may be due to an autoimmune dysfunction, rather than a primary psychiatric illness. This distinction is critical since treatment differs for each.

"Neuronal autoimmune responses and inflammation in the brain can be a root cause of certain neuropsychiatric symptoms," said Craig Shimasaki, Ph.D., President and Chief Executive Officer of Moleculera Labs, sole provider of the Cunningham Panel™ of tests.

"If the autoimmune condition is correctly identified, the underlying cause behind these disruptive behaviors has been successfully treated with anti-infective and immune modulation therapies, rather than managing the symptoms with psychotropic drugs," added Dr. Shimasaki.

An estimated 17 million, or 1 out of every 5 children in the U.S., currently have or have had a seriously debilitating mental disorder, according to the NIMH.

However, researchers believe a significant percentage of these children have an undiagnosed and treatable autoimmune dysfunction causing their neuropsychiatric condition.

Now, the Cunningham Panel™ is helping identify this group of patients, by providing clinicians with objective laboratory evidence of a patient's autoimmune and anti-neuronal status.

The biomarker tests in the panel measure the levels of autoimmune antibodies directed against specific neurological targets in the brain associated with certain movements, behaviors and cognitive processes.

"It has long been known that through a process called molecular mimicry, Streptococcal infections can trigger immune responses that generate autoantibodies against certain human antigens in the heart or brain.

This autoimmune reaction can result in damage to heart valves, or in the case of the brain, the neurologic disorder Sydenham chorea," explained Dr. Cunningham, chief developer of the Moleculera panel and for whom it's named.

"There is increasing evidence that infection-triggered autoimmune and inflammatory reactions may affect neuronal cells in the basal ganglia of the brain and may also cause sudden-onset obsessive-compulsive behaviors and movement disorders in children," she added. "Moreover, such conditions may be associated with other infections besides Streptococcus, such as influenza, Lyme disease and mycoplasma."

According to the PANDAS Physicians Network, this growing body of research has led the National Institutes of Health/National Institute of Mental Health (NIH/NIMH) to develop a consortium of 14 proposed multidisciplinary sites dedicated to studying and treating children with infectious and postinfectious autoimmune encephalopathy-like disorders, including Pediatric Acute-onset Neuropsychiatric Syndrome (PANS) and Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal infections (PANDAS).

Last month, the first site located in the Southwest officially opened. The Children's Postinfectious Autoimmune Encephalopathy Center of Excellence at the University of Arizona's Steele Children's Research Center expects to serve about 30 pediatric patients per month.

The Cunningham Panel™ was instrumental in helping diagnose the Center's first patient, an 8-year-old girl, who after several bouts of infections had a sudden onset of debilitating anxiety, fears and OCD which progressed to severe anorexia.

"The Cunningham Panel™ confirmed the PANDAS diagnosis and put us on the correct treatment path," said Karen Blandini, the child's mother. "Without it we were lost."

The Panel's test results revealed elevated levels of certain autoantibodies associated with the young girl's emotional, cognitive and behavioral symptoms. Once correctly diagnosed, she was treated at the new Arizona Center, given immune-modulating therapies and experienced a complete recovery.

"The advantage of this type of panel is that it identifies specific antibodies to specific neural elements," explained Dr. Richard Frye, Director of Autism Research at Arkansas Children's Hospital Research Institute. "Most importantly high-quality scientific studies have identified these antibodies and linked them to disease. This type of test gives us more specific information that leads to the diagnosis of an autoimmune encephalopathy."

The Cunningham Panel™ consists of five tests ─ four assays measure circulating levels of autoantibodies directed against specific neuronal antigens, including Dopamine D1 receptor (DRD1), Dopamine D2L receptor (DRD2L), Lysoganglioside GM1, and Tubulin. Autoimmune antibodies that bind to these targets may disrupt the functioning of these antigens, which can trigger abnormal neurologic and psychiatric behaviors, such as OCD, tics, anxiety and other mood disorders. The fifth assay measures the level of CaM Kinase II (CaMKII) activity. CaMKII is a key enzyme involved in the up-regulation of many neurotransmitters such as dopamine.