MS: Probable Cause and Best Bet Treatment

BEST BET DIET BOOK
Scientific Papers

"MS: Probable Cause and Best Bet Treatment" Dr. Ashton Embry © 1996
Section 6: Pathogenesis of MS
In the last section the epidemiological evidence for dietary factors as the main cause of MS was presented. Of course, if diet is the main cause, it must be demonstrable that specific dietary factors are capable of resulting in the various known disease processes of MS. In this and the next sections the basic disease processes (pathogenesis) of MS are reviewed and the theoretical basis for dietary factors resulting in these processes are presented. The basic pathogenesis of MS involves the entry of immune cells (e.g. T-cells, B-cells, macrophages) into the CNS through the walls of the capillaries and venules (Traugott, 1990; Poser, 1993). Immune reactions occur, a lesion is formed and myelin is eventually destroyed. Myelin consists of fatty tissue which wraps around nerve axons. It essentially acts as nerve insulation and is critical for proper nerve transmissions. Loss of myelin results in degradation of nerve transmissions and a resultant multitude of disabilities which gradually worsen over time as more myelin is destroyed. It is very important to note that in healthy individuals immune cells cannot pass through the CNS capillaries and venules into the CNS tissue. This does not happen because the walls of the capillaries in the CNS are different from those in the rest of the body in that they have very closely packed cells which do not allow the passage of immune cells. This special feature of the CNS vascular system is referred to as the blood-brain barrier (BBB) (Traugott, 1990). It would seem that an intact blood-brain barrier prevents CNS infiltration of immune components and thus stops the possibility of MS occurring. As noted by Compston (1991), one of Britain's leading MS researchers, "blood-brain barrier penetration can be regarded as the primary disease process". This is especially true because many people carry immune cells which are reactive with brain tissue but only a few develop MS. As explained by Soll (1968) many years ago, "isolation (of the CNS) begins to take place during fetal life, very likely before the so-called immunologic "recognition of self" takes place. Thus, at least parts of our brain may be capable of evoking an immune reaction... provided the immune mechanisms were allowed direct access to the CNS". Thus almost 30 years ago it was recognized that a critical disease process in MS is the breach of the BBB and the exposure of the CNS to autoreactive immune cells. This concept is now widely accepted and Theofilopoulos (1995b) notes in a recent, comprehensive review of autoimmune disease "Induction of autoimmune disease, following contact with antigens of such so-called "immunological privileged" sites, has been well documented". This concept has been supported by observations of MS lesions on MRI scans. On the MRI scans it was observed that the CNS lesions could be enhanced by using gadolinium-DTPA (Miller et al., 1988; Kermode et al., 1990). Passage of this substance through the BBB clearly indicated that the MS lesions in the CNS occur where the BBB has been damaged so that various substances, including gadolinium, could readily pass through the damaged walls of the capillaries. Furthermore, Traugott (1990) notes "that MS lesions are preferentially localized around postcapillary venules" which have a "relatively low barrier function". This and other evidence led Poser (1987, 1992, 1993), in a series of watershed papers, to declare in no uncertain terms "In order for MS to become a disease affecting the CNS, it is necessary for the blood-brain barrier's impermeability to be altered" (Poser, 1993, p. 53). Recently, this emphasis on the damage to the BBB as a key disease process in MS has been confirmed by Lai et al. (1996). Based on a study of weekly MRI scans in patients, these researchers state that "this finding suggests that breakdown of the blood-brain barrier is an invariable and perhaps obligatory event in the development of new lesions". A second part of MS pathogenesis, which is more controversial, is the cause and timing of the activation of the autoreactive T-helper cells (a type of immune cell strongly implicated in MS pathogenesis [Traugott, 1990]) which react to the CNS proteins. Two possibilities have been advanced. One hypothesis is that the T-cells are activated in the blood outside of the CNS and these cells then cross the BBB to attack the myelin or other CNS proteins. The other hypothesis, which has been alluded to earlier, is that the autoreactive T-cells become activated against CNS proteins after they have passed through a breach in the BBB and encounter the previously sequestered CNS proteins. To me it is most likely that many of the pathogenic, autoreactive T-cells are activated outside of the CNS. My reasoning for this conclusion is that MS is just one of many autoimmune diseases and many of the others have only the presence of a normal capillary wall between the blood and the tissue. These diseases require activation of the T-cells outside the tissue and, thus, I believe such a requirement also is the most reasonable assumption for MS. The cause of the activation of T-cells against CNS proteins outside the CNS is somewhat problematic. The most widely accepted hypothesis (Theofilopoulos, 1995b) is that peptides (fragments of proteins) from foreign antigens which are presented by macrophages (another type of immune cell) to T-cells may resemble parts of CNS self proteins from a molecular structure point of view. This is referred to as molecular mimicry as was mentioned earlier. Experimental data have clearly shown that such a mechanism by both food and viruses can result in the activation of T-cells against various self proteins (Singh et al., 1989; Wucherpfennig et al., 1995; Ostenstat et al., 1995). Thus molecular mimicry would indeed appear to be a critical factor in the pathogenesis of MS. In summary, the evidence is strong that a key part of MS pathogenesis is the activation of autoreactive T- cells both outside and within the CNS and that persons with MS carry such CNS autoreactive T-cells. These activated T-cells set in motion a series of immune reactions which results in myelin being destroyed by various immune elements (e.g. macrophages) (Traugott, 1990). The interested reader is referred to Steinman (1993) for an excellent review of autoimmune disease in general and multiple sclerosis in specific. Other articles in the same issue of Scientific American provide a good overview of immunology.
End section 6.