By Avigayil Kadesh
Neuroscientists have long believed that cells of the immune system are harmful to the brain. So when someone suffered a spinal cord injury or a neurodegenerative disease such as Alzheimer’s, Parkinson’s or ALS, doctors would prescribe anti-inflammatory drugs to prevent the immune response to that ailment from getting to the brain.
Israeli neuro-immunologist Prof. Michal Schwartz suffered years of ridicule for questioning that approach because she felt it was illogical. Now, her research is gaining attention and respect even though it is proving long-held beliefs incorrect.
“I decided to examine this dogma from an evolutionary standpoint,” says Schwartz, who reasoned that the brain must be wired with a protective mechanism against harmful effects of the immune system.
“Scientists/clinicians now know how to transplant almost every organ in the body, other than the brain. It was hard for me to believe that an organ that cannot be replaced would so severely lack a system to help it heal.”
n fact, she and her colleagues have made the groundbreaking discovery that immune cells help with tissue maintenance and neuron creation in the brain. When immune cells are blocked from the brain – even in natural processes seen in aging – this may contribute to cognitive decline and conditions such as Alzheimer’s disease.
A protein that blocks immune cells from the brain
A
study recently published in the journal Science by Schwartz and her colleague Dr. Ido Amit at Israel’s Weizmann Institute of Science, along with graduate students Kuti Baruch and Aleksandra Deczkowska, describes how older mice had elevated levels of a unique protein, interferon beta, in the choroid plexus lining between their brains and their circulatory blood supply.
This protein acted as a barrier between the mice’s immune system and brain, and seemed to impair their cognitive abilities. Neutralizing the protein – which has also been found in elevated levels in autopsies of elderly people -- allowed for partial restoration of the mice’s lost cognition.
Schwartz and her team have thus shown that the brain does coordinate with the immune system through the choroid plexus, but in a way that is different than in the rest of the body.
“Think of a gate through which only those with a passport can enter,” she says. “This ‘passport’ checks which cells may enter, and adjusts their activity so that they do what the brain needs them to do, and not what the brain does not want them to do.”
She hypothesizes that the immune system actually plays an essential daily role in keeping the brain healthy and protected from degeneration.
“After all, the brain is always going out of balance, either due to positive activities or due to mini-traumas and stress, yet most of us regain equilibrium quite quickly,” she says. “In other words, something must be working to restore the balance in our brains. And that something is the immune system.”
Better immune system, better brain healing
However, as we age, the delicate dance performed in the choroid plexus may falter. When that happens, the immune response that once shielded the brain can go awry and cause cognitive damage. The Weizmann team may have found a target for future therapies to restore the proper choreography.
Schwartz explains that when the immune system fails to function properly, we are more susceptible to post-trauma and degenerative diseases. “Boosting the immune system, then, should be able to protect the brain from anxiety, depression and degeneration.”
Moreover, her team’s research suggests that a well-functioning immune system can protect the brain from the effects of aging – and vice-versa.
Working on that premise, Schwartz established
Proneuron Biotechnologies in 1996. Trying her best to ignore two decades of opposition from peers who dismissed her notions – and picking up a few international awards along the way -- she has been trying to find a method of enhancing the immune system as a possible cure for Alzheimer’s disease.
Though this goal is still many years from fruition, Schwartz has always stuck with her gut feeling that maintaining a healthy immune system, rather than tackling the pathology of brain-related injury and illness, is the key to a reversal of conditions once deemed incurable.
Schwartz was the first to claim that the integrity of the immune system is pivotal for neural tissue survival and repair. She pioneered the concept of “protective autoimmunity” and its role in central nervous system maintenance, cognitive and mental activity, and cell renewal from adult stem cells.
“I suffered a lot,” she says regarding the scientific community’s rejection of her theories. “But my intuition that I was looking in the right direction was strong.”