Immunotherapy for autoimmune antibody associated psychosis

A trial using immunotherapy for individuals with psychosis and brain-reactive autoantibodies, in whom encephalitis has been excluded, has opened and is beginning to screen individuals across the UK.

At present there are no major disease modifying treatments for schizophrenia (a cause of psychosis) and so immunotherapy could have significant clinical implications for patient care.

The trial, funded by the MRC is being led at UCLH by Dr Michael Zandi and his team. Earlier findings from the team show that patients with certain type of autoimmune encephalitis have psychiatric and neurological symptoms. These patients were found to have antibodies that attack the individual’s own NMDA receptors – which carry electrical signals in the brain. Autoantibodies are seen in 1-10% of first episode psychosis cases with many developing schizophrenia. Patients with such antibodies do not respond well to anti-epileptic and anti-psychotic therapies; however, they respond excellently to immunotherapies.

Dr Zandi who receives BRC support explained the importance of the trial: “These individuals make excellent clinical responses to immunotherapies, where symptomatic therapies (anti-epileptic or anti-psychotic drugs) have no effect. NMDA receptor and related antibodies are found rarely in healthy individuals but are found in individuals with neurodegenerative disease. We therefore do not know if the presence of serum antibodies in individuals with relatively isolated psychosis are disease-relevant, and a marker of a group of individuals with an inflammatory aetiology who will respond to immune therapies, or if the antibodies are red-herrings.”

The trial will be carried out in individuals aged 18-70 with acute psychosis and serum synaptic autoantibodies, in whom encephalitis has been excluded. The trial is being run at three treatment hubs – the UCLH Leonard Wolfson Experimental Neurology Centre, Addenbrooke’s Hospital and the John Radcliffe Hospital in Oxford.