Posted on Jan. 17: Scientist awarded $400,000 grant to study lupus
[img_inline align=”right” src=”http://padnws01.mcmaster.ca/images/Sakic.Boris.jpg” caption=”Boris Sakic”]McMaster University researcher Boris Sakic has been awarded more than $400,000 Cdn to study mechanisms of brain damage in an autoimmune disease.
The assistant professor of psychiatry and behavioural neurosciences
along with four American researchers have been awarded separate grants
to study this aspect of an autoimmune disease known as systemic lupus
erythematosus. The grants were from the U.S. National Institute of
Arthritis and Musculoskeletal and Skin Diseases (NIAMS), of the National Institutes of Health (NIH).
Lupus is a disease which can be fatal, and in which immune cells become confused. Instead of protecting the body by attacking bacteria or virus, they start to attack the body's own cells by producing proteins called autoantibodies. When the brain becomes the target this often results in psychosis, depression and memory loss.
Sakic's recent research indicates that when immune cells get access into the brain, they destroy neurons and, more importantly, the neural stem cells needed for normal brain development and repair by producing toxic autoantibodies. This brain damage may occur in the parts of the brain that control emotions, memory, and hormone release.
These findings are exciting because researchers have believed that
autoantibodies may bind to the brain tissue and cause certain forms of
schizophrenia, Alzheimer's disease, epilepsy, and autism. This theory
hasn't gained much attention by the scientific community because of
inconsistencies and unknown factors that were never fully identified in previous studies.
The present work is a major leap forward, says Sakic, because there is
now evidence that an abnormal immune system may interfere with the
brain's growth and function.
“While there's still much to be understood, we know a great deal more
about the ways immune systems may destroy brain tissue,” says Sakic.
“It has long been believed that neurons, the main cells responsible for proper brain function, can't be recovered if lost after birth. But recently it has been discovered otherwise.
“In fetuses, neural stem cells are plentiful. They remain in small
numbers until adulthood and are kept, as an emergency supply of sorts,
to help replenish cells that might die due to aging or brain disease. We believe that autoantibody-induced destruction of these cells before or after birth might result in underdevelopment of the brain and abnormal brain function.
“For the first time we show that it is possible for these cells to be
destroyed by the immune system.
“We hope that by continuing to research this discovery, we can gain a
greater understanding of degenerative brain disorders for which
medication often does not work,” says Sakic. “New treatments based on
these findings could mean prevention of mental illness in people who
have over-active immune systems.”
The research has involved chemically separating parts of the brain fluid from mice to test the role autoantibodies play in the toxicity of the brain fluid. Sakic and collaborator Laurie Doering and their team were able to conclude that the death of brain stem cells correlates with toxicity in the brain fluid. They also confirmed the phenomenon in a patient with neuropsychiatric lupus.
Next, Sakic plans to examine exactly where on the surface of a cell these toxic antibodies attach themselves, and how this is relevant to abnormal behaviour.
“The best approach to test cause-and-effect will involve isolating
deadly immune cells so we can see more closely how the brain damage of
neural stem cells occurs,” says Sakic.
Sakic is a member of the McMaster's Lupus Research Group, which includes colleagues Judah Denburg, Henry Szechtman and Susan Denburg. The ultimate goal of this group is to improve treatments and ease suffering for people who have neuropsychiatric lupus and potentially, for the ones with classical mental illness.
