June 4, 2001
Identifying the trigger that results in the devastating loss of motor and sensory functions called multiple sclerosis is the focus of Medical College of Georgia researchers.
By identifying the trigger mechanism that causes the body's immune system to attack the fatty tissue called myelin which insulates nerves, researchers hope they can stop it.
"This is a very devastating disease that affects primarily young adults and can last for many years with great costs in terms of quality of life and care," said Dr. Robert K. Yu, director of the Institute of Molecular Medicine and Genetics, who just received a one-year, $32,241 grant from the National Multiple Sclerosis Society for his studies.
He is looking at normal constituents of the myelin membrane as trigger suspects and determined that a group of compounds called glycolipids, composed primarily of sugars and fats, are one likely candidate.
"These are ubiquitous cells that participate in a lot of common cell functions such as cell recognition, adhesion and migration," Dr. Yu said. Utilizing the same principle as a vaccination – injecting a small amount of a harmless, dead virus so the immune system will mount a protective response to that virus – Dr. Yu has immunized laboratory animals with glycolipids.
Early results show that the animals develop a multiple sclerosis-like condition. These animals may prove to be a model for further study of the disease that impacts the multiple layers of the fatty myelin that insulate nerves throughout the central nervous system, greatly increasing nerve conduction and preventing leakage of electrical current. Without myelin, nerves become inefficient and ineffective.
Myelin formation begins before birth and continues through adolescence, Dr. Yu said. Patients with multiple sclerosis experience a destruction of myelin that often surfaces with difficulty seeing, because the optic nerves are affected, and can eventually lead to a loss of body control. Neurons are not affected, so the disease does not impact intelligence.
Patients can experience periods of remission, during which time cells that make myelin, called oligodendrocytes, can rebuild at least a couple of layers of the protective, fatty substance. This respite lasts until the immune system again sends antibodies and cytotoxic T-cells in for another attack.
Dr. Yu, who also has funding from the Children's Medical Research Foundation of Chicago, also is trying to promote re-myelinization by transplanting the stem cells of these oligodendrocytes to the site of myelin loss. Current drug therapies promote remyelinization by suppressing the immune system, inducing a form of remission that enables the myelin to rebuild. Cytokines also are prescribed to help stop the synthesis of the cytotoxic T-cells.
Young, white women are at highest risk for the disease; some population groups, such as Asians, have a comparatively low risk. Genetic risk factors include abnormalities in myelin composition and/or problems with regulation of the immune system. But virologists across the world also are trying to determine if the aggressive, destructive response of the immune system is triggered by a virus, possibly even influenza or canine distemper virus, Dr. Yu said.
An immune response to a virus or other infection resulting in an attack of the body's own tissue may result from something called molecular mimicry. "You might be infected by a microorganism, such as a virus, that will cause an immune response, but if the resulting antibodies also recognize body constituents – similar in their structural makeup to the virus – that is what we call molecular mimicry," he said.
Other questions are being pursued as well, such as how antibodies, which are big molecules circulating in the blood, cross the natural blood-brain barrier that typically protects the brain from such invaders. "Luckily your brain is well-protected," he said. "The problem is how the antibody can penetrate from the circulation to the nervous system."