In 2006 we set our goal to find the cause of MS in five years. So we have to find the cause this year! How close are we and what are we doing? Our approach is based on the finding that over 90% of MS patients have antibodies (oligoclonal bands) in spinal fluid. These antibodies are not randomly present and it is known that they are produced within the brain and spinal cord and are closely related to each other, suggesting that they have a common target (that is what oligoclonal means). These oligoclonal antibodies are important to study because in every condition other than MS in which similar antibodies are found, such as in measles, they are targeted toward the cause of the illness. Thus, our assumption is that if we find out what these oligoclonal antibodies in MS are targeting, it will be the cause of MS or at the very least the key brain target protein (antigen). This assumption is also based on certain immunological dogma. When the immune system is “activated” and reacting to a specific target, the body produces select antibodies that are clones of each other to enable a highly specific and effective response. This phenomenon is called clonal expansion and a persistent clonal response is highly suggestive of purposeful, targeted amplification of the immune system. Thus, we aim to isolate clonally-expanded and persistent B-cells from patients with MS, mass produce them in the lab to allow detailed experimentation without repeated spinal taps, and determine their reactivity against all plausible targets. Identification of this target should be the critical link to finding the cause of MS.
Jerry Lin, a B-cell molecular immune-biologist in our laboratory, along with his research assistants have accomplished the following in the past 5 or so years:
1) Using FACS analysis, they have been able to reliably isolate B-cells; 2) Using recombinant technology and sequencing, they have been able to determine which B-cells are clonally expanded and if spinal fluid is repeated at a later time point detect clonally expanded B-cells that persist; 3) They have isolated, sequenced and cloned single antibody producing cells from selected MS patients and a disease control (patient with HTLV-1 myelopathy). The MS patients selected include two teenage patients with disease onset a few weeks prior to CSF collection; an unusual patient with radiological evidence of MS who has had no clinical manifestations as yet (pre-MS); a very early in disease PPMS patient, and two patients with long standing disease; 4) They have established somewhat surprisingly that the target antigen or initiating trigger is probably not present in brain or spinal cord.
We have made significant strides in this endeavor and are hopeful that in the next few months we will be able to identify the initial trigger of MS. This is important because if identified, we can develop a “vaccination” approach that can prevent the development of MS.