Antibody May Be Key in Slowing Multiple Sclerosis Demyelination
Scientists at the Mayo Clinic believe an enzyme known as Kallikrein 6, abundant in multiple sclerosis (MS) lesions, may be neutralized by an antibody which then could slow the demyelination process characteristic of the neurodegenerative disease.
Multiple Sclerosis is an autoimmune disease that affects the central nervous system. It is caused when inflammation damages the myelin sheath, the protective covering that surrounds nerve cells. When the covering is damaged (deymyelination), nerve signals may slow down or stop.
Previously, researchers in the Department of Physical Medicine and Rehabilitation at the Mayo Clinic found an enzyme called Kallikrein 6, a secreted serine protease with diverse physiological functions. Klk6 is associated with the inflammation and demyelination in MS, and may also be implicated in Alzheimer’s disease and some cancers.
The same team, led by Isobel Scarisbrick PhD, have found an antibody that may neutralize Klk6, thus slowing MS progression. The scientists evaluated the process in mice infected with the Theiler's murine encephalomyelitis virus (TMEV). This virus induces encephalomyelitis comparable to multiple sclerosis. The model is based on the theory that viral infection early in life results in eventual abnormal immune response in the brain and spinal cord.
One week after being infected with the virus, the mice had elevated levels of Klk6. However, the neutralizing antibody blocked the enzyme, and the mice also had reduced inflammatory white blood cells and slowed depletion of myelin basic protein.
“These findings suggest Kallikrein 6 plays a role in the inflammatory and demyelinating processes that accompany many types of neurological conditions,” says Dr. Scarisbrick. “In the early chronic stages of some neurological diseases, Kallikrein 6 may represent a good molecule to target with drugs capable of neutralizing its effects.”
Scarisbrick, I. A., Yoon, H., Panos, M., Larson, N., Blaber, S. I., Blaber, M. and Rodriguez, M. (2012), Kallikrein 6 Regulates Early CNS Demyelination in a Viral Model of Multiple Sclerosis. Brain Pathology. doi: 10.1111/j.1750-3639.2012.00577.x