A great deal of evidence has been accumulated over the last several decades that abnormal immune reactions against myelin proteins can be detected in patients with MS. Although antibodies to myelin are common in patients with MS, they are also common in patients with other disorders as well.
The occurrence of inflammatory disease of the brain and spinal cord (acute encephalomyelitis) following infections and immunizations (especially after a killed virus rabies vaccine made from rabbit spinal cord) led to studies of the “allergic” potential of certain proteins in the nervous system.
Most research has been focused on a single protein, myelin basic protein, because it has a high potential for the induction of experimental demyelinating disease in rats, guinea pigs, monkeys, and other animals.
Only 10 millionths of a gram (there are 450 grams in a pound) injected into a genetically susceptible rat can result in experimental disease resembling MS. Over 30 years ago we found that MS patients have cells reactive to this protein in their blood. More recently, Swedish scientists have also found cells with similar reactivity in the spinal fluid of MS patients.
Importantly, the original research into a treatment now approved for use in MS (Copaxone) arose from this work. Copaxone is a synthetic “fake” brain protein that serves as a decoy to redirect immune reactions away from myelin basic protein in myelin.
In recent years, other nervous system proteins have been implicated in autoallergic central nervous system diseases. A large myelin protein (proteolipid) has been used to induce experimental disease.
A dozen and a half mutations (which are changes in the structure of the DNA with the potential to alter the normal function of the gene) of the gene coding for this protein have been found in different families with familial infantile spastic paraplegia, a nervous system disease than superficially resembles MS.
Despite this advance in understanding of those rare disorders, it does not seem to have any importance in MS. We have found that immune responses to this protein in MS patients are difficult to detect and when found do not occur more commonly than in patients with other nervous system diseases.
Currently, a great deal of interest is being focused on another protein, which has recently been found in miniscule quantities in the central nervous system called myelin oligodendrocyte glycoprotein (MOG).
Monkeys immunized with MOG protein have a dis-ease more closely resembling the human disease than disease induced with myelin basic protein. Moreover, in recent unconfirmed studies, antibody to this protein has been reported to be present in the blood of patients with their very first manifestation of illness (MS). This is particularly important because MOG antibody is capable of transferring disease in primates.
Antibody to MOG is found in a high proportion of MS patients with progressive disease, also. This finding makes its significance more difficult to understand. Research continues without a firm role for anti-MOG antibody being established. However, there is a suspicion that immune reactions to this protein may be of importance in a subset of patients in whom antibody appears to be playing a central role.