Researchers at the Queen Mary University of London and the University of Roehampton, London report finding a potential antibody treatment against obsessive compulsive disorder (OCD) — in mice.
The team reports that human patients suffering from OCD show increased levels of a protein called Immuno-moodulin (Imood) in lymphocytes, a type of immune cell. Mice whose lymphocytes were modified to show the same high levels of Imood showed behaviors that are characteristic of anxiety and stress, such as digging and excessive grooming, which are related to OCD.
However, the team also showed that an antibody can be used to neutralize the protein, which reduced the animals’ apparent anxiety levels in lab tests. The findings might help us develop a similar treatment for humans.
There’s a pill for that
“There is mounting evidence that the immune system plays an important role in mental disorders,” said Professor Fulvio D’Acquisto, a professor of immunology at the University of Roehampton and honorary professor of Immunopharmacology at Queen Mary University of London, who led the research. “And in fact people with auto-immune diseases are known to have higher than average rates of mental health disorders such as anxiety, depression and OCD.”
“Our findings overturn a lot of the conventional thinking about mental health disorders being solely caused by the central nervous system.”
Professor D’Acquisto first identified Imood by chance while studying a different protein (Annexin-A1) and the role it plays in autoimmune diseases such as multiple sclerosis and lupus. As part of the study, he engineered lab mice to overexpress this protein in their immune cells in the hopes of inducing autoimmune diseases in the animals and found that the mice were more anxious than normal. Upon closer inspection, the team found that one protein was especially active and likely protected the animals from such diseases.
Curious about its effects, the team administered an antibody treatment to the mice that would block the Imood gene — and their behavior returned to normal within a couple of days. This led the team to christen the gene encoding it “Immuno-moodulin”.
Later on, the team tested the immune cells of 23 patients with OCD and 20 healthy volunteers to check if they showed any differences in Imood levels. OCD patients had around six times higher expression of these genes than the controls. Together with previous findings, the team is confident that this showcases the role this protein has in mental health disorders such as OCD or ADHD (Attention-Deficit/Hyperactivity Disorder).
The team believes that the gene encoding the protein doesn’t directly influence brain functions, but that its activity is tied to that of other genes in brain cells that are linked to disorders like OCD.
“This is work we still have to do to understand the role of Imood,” says Professor D’Acquisto. “We also want to do more work with larger samples of patients to see if we can replicate what we saw in the small number we looked at in our study.”
“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,” he adds.
The team is collaborating with the biopharmaceutical company UCB to develop antibodies against Imood that can be used in humans and to understand how this could be used to treat patients with mental disorders. Professor D’Acquisto estimates it could take up to five years before a treatment is ready for clinical trials.
The paper “Immuno-moodulin: A new anxiogenic factor produced by Annexin-A1 transgenic autoimmune-prone T cells” has been published in the journal Brain, Behavior, and Immunity.
