Antibodies as Potential Therapy for Obsessive Compulsive Disorder

Antibodies for OCD Therapy

Source

• Queen Mary University of London

Highlights

• Transgenic mice overexpressing Annexin-A1 in their CD4+ T cells developed anxiety like behavior.
• Gene expression analysis of the mice’s CD4+ T cells revealed hyperactivity of a gene producing this novel protein named “Imood”.
• The mice’s anxiety like behavior was successfully reverted to normal using antibodies against Imood.
• Imood expression levels appeared to be 6 times higher in obsessive-compulsive disorder (OCD) patients than healthy control subjects.

Immuno-moodullin - The Over-expressed Protein in Obsessive Compulsive Disorder

Researchers at Queen Mary University of London and the University of Roehampton, London, have unpredictably identified a particular protein found over-expressed in OCD patients’ lymphocytes, as they decided to name it “Imood” as short for “Immuno-moodullin”.

It is known that patients of auto-immune diseases are more likely to develop mental health disorders such as anxiety, depression and obsessive-compulsive disorder (OCD), in which the underlying cellular and molecular mechanisms linking these pathologies are yet to be discovered.

The Discovery by Coincidence

This unique protein was discovered by coincidence while studying the impact of Annexin-A1 protein in auto-immune disorders, for this aim the researchers generated transgenic mice over-expressing Annexin-A1 in their CD4+ T cells, which exhibited later an increased level of anxiety translated by a high compulsive digging and excessive plucking of fur, believed to be homologous to human trichotillomania and OCD.

Analysis of gene expression in the mice’s CD4+ T cells revealed a hyperactivity of a particular gene producing a protein of approximately 21kDA stored in vesicles and present in circulation, which they eventually called “Imood”.Treatment with neutralizing polyclonal and monoclonal antibodies reverted the behavior of the anxious transgenic mice to normal in a couple of days and lowered basal levels of anxiety in wild type mice.

Higher Imood Expression in Obsessive Compulsive Disorder

The scientists finally investigated this protein in humans where they analyzed the T cells of 23 OCD patients in comparison to those of 20 healthy controls, finding that Imood expression levels in OCD patients’ peripheral mononuclear cells were 6 times higher than controls in both male and female subjects. These findings support results of a different research highlighting the overexpression of the same protein in Attention Deficit Hyperactivity Disorder (ADHD) patients.

CD4+ T cells exert a homeostatic control over a variety of brain functions notably learning, memory and anxiety-like behavior, thus identifying this protein as a novel determinant modulating anxiety , and therapy targeting immuno-moodullin as a promising unconventional treatment for mental disorders through regulation of anxiety associated genes rather than directly modulating neurotransmitters activity in the brain.

Imood could possibly offer in addition a novel biomarker of prognostic and diagnostic value facilitating mental disorder classification of patients or identification of their adequate subgroup for specific drug treatment. Per se, a combinational therapy with immunomodulators and Imood neutralizing antibodies.

"It is early still, but the discovery of antibodies instead -of the classical chemical drugs – for the treatment of mental disorders could radically change the life of these patients as we foresee a reduced chance of side effects" said, Professor Fulvio D’Acquisto, professor of immunopharmacology at Queen Mary University of London and leader of this research who is currently cooperating with Dr Dianne Cooper, a Senior Lecturer at Queen Mary University of London, and the biopharmaceutical company UCB to develop antibodies against Imood for humans and to understand how it could be used to treat patients with mental disorders. Estimating it could take up to five years before a treatment can be taken to clinical trials.

Journal Reference

• Piras, G., Rattazzi, L., Paschalidis, N., Oggero, S., Berti, G., Ono, M., Bellia, F.,D'Addario, C., Dell'Osso, B., Maria Pariante, C., Perretti, M., D'Acquisto, F., Immuno-moodulin: a new anxiogenic factor produced by Annexin-A1 transgenic autoimmune-prone T cells, Brain, Behavior, and Immunity (2020), doi: https://doi.org/10.1016/j.bbi.2020.02.015