This Is MS Multiple Sclerosis Community: Knowledge & Support

....questions have been raised as to whether inflammation and/or autoimmunity are really at the root of the disease, and it has been proposed that MS might in fact be a degenerative disorder. We argue that MS may be an 'immunological convolution' between an underlying primary degenerative disorder and the host's aberrant immune response. To better understand this disease, we might need to consider non-inflammatory primary progressive MS as the 'real' MS, with inflammatory forms reflecting secondary, albeit very important, reactions.

One might reasonably ask why other common neurodegenerative disorders, such as Alzheimer’s disease and Parkinson’s disease, do not also result in relapsing–remitting neuroinflammation. In fact, both diseases do exhibit inflammation in pathologically vulnerable regions 83,84. Indeed, in these research fields there is also an ongoing debate about whether inflammation is a reaction to, or cause of, ongoing degeneration. For example, post-mortem examination of human and primate brains after exposure to MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine), a neurotoxin that induces parkinsonian features by killing dopaminergic neurons, reveals a sustained inflammatory response that continues for years after exposure to the toxin 85,86. Clearly, in this example the initiating insult was a monophasic degenerative one (toxin-induced death of a specific neuronal population), which secondarily entrained a protracted inflammatory reaction and, interestingly, continued neurodegeneration that long outlasts the toxic insult. The reasonable question that was raised was whether such secondary inflammation could now feed back and promote further degeneration, completing an analogous ‘inside-out’ cycle as we propose for multiple sclerosis (MS) (FIG. 1). Because diseases such as Alzheimer’s and Parkinson’s have a much more prominent degenerative rather than inflammatory phenotype, the initial assumption was that a degenerative mechanism (or mechanisms) was primarily responsible, with inflammation perhaps a secondary, but possibly important, consequence of the degeneration. In MS, the situation is reversed: inflammation occurs early and is very prominent in many patients, so it was naturally assumed that autoimmunity might be causal; but, as we argue throughout this Perspective, such an assumption may be incorrect. If MS is primarily a degenerative disorder in line with an inside-out mechanism, why would this disease be unique in engendering such prominent and cyclic inflammation? The differences may be related to age: Alzheimer’s disease and Parkinson’s disease present decades later than MS, and immune responsiveness wanes with age through a process of ‘immune senescence’ (REFS 21,87). Indeed, the responsiveness of T cells, which are known to be centrally involved in the immunopathogenesis of MS 88, appears to be particularly altered with age 87. Moreover, it is conceivable that the putative cytodegeneration involving the myelinating unit (oligodendroglia, their processes and myelin) in MS releases debris that is more antigenic 35,36,66 than the debris that is shed from the mainly synaptic and neuronal degeneration in Alzheimer’s disease and other traditional neurodegenerative disorders.

"This study hypothesizes that the inflammatory response in MS is the result of an underlying degenerative process rather than the primary cause of injury," says Dr. Peter Stys, lead researcher, Department of Clinical Neurosciences, University of Calgary. "In other words, an underlying mechanism causes degeneration that prompts the inflammatory process, which in turn causes more degeneration."

Cheer,


It's nice to see that MS research has been branching out in other directions the past few years. While this new theory certainly needs to be proven, let's hope it leads to the long awaited cure.

Harry

How does one cure a degenerative disease? Have any other neurodegenerative diseases ever been cured?

"While the search for a pharmaceutical cure plays front and center, quietly in the background countless neuroscientists worldwide have concluded that Alzheimer's, as well as memory decline and other age-related dementias are actually slow-developing chronic diseases, like heart disease and cancer, partly dependent on lifestyle and other treatable diseases.

I have discovered a large contingent of Alzheimer's researchers who are extremely positive about prevention and not counting on an elusive drug to stymie the growing Alzheimer's epidemic of aging baby boomers. Investigators Gregory Cole and Sally Frautschy at UCLA's Center for Alzheimer's Research and Gary W.Arendash, PhD, at the Florida Alzheimer's Research Center, for example, are all focusing on prevention. There is a plethora of upbeat dialogue in the scientific community that does not grab headlines because it's not about big money and a magic cure. It's primarily about what people can do to change their own trajectory toward Alzheimer's.

De la Torre, for example, is convinced that Alzheimer's and dementia are particularly tied to cardiovascular factors, notably, constricted blood flow to brain cells, and that midlife screening to detect and correct such heart-related deficits would help prevent much brain degeneration during aging. The special journal issue produced by de la Torre, called "Basics of Alzheimer's Disease Prevention," also included new research on the relationship between Alzheimer's and diabetes, high blood pressure, triglycerides, cholesterol, and the effects of a Mediterranean diet, exercise, fish oil, B vitamins and antioxidants.

How does one cure a degenerative disease? Have any other neurodegenerative diseases ever been cured?

Indeed, the failure of potent immunosuppression to affect later, progressive MS suggests that a primary cytodegenerative mechanism could be a more plausible initiating event, and progressive non-inflammatory MS (that is, primary progressive MS) may thus be most reflective of the real underlying disease.

Finally, these arguments have fundamentally important implications for therapeutic design. Using EAE to test and develop drugs to treat MS will naturally bias the outcome towards effective anti-inflammatory agents,without necessarily engineering in effectiveness against degenerative processes; this has been our experience to date with MS therapeutics.

In MS, the situation is reversed: inflammation occurs early and is very prominent in many patients, so it was naturally assumed that autoimmunity might be causal; but, as we argue throughout this Perspective, such an assumption may be incorrect. If MS is primarily a degenerative disorder in line with an inside-out mechanism, why would this disease be unique in engendering such prominent and cyclic inflammation? The differences may be related to age: Alzheimer’s disease and Parkinson’s disease present decades later than MS, and immune responsiveness wanes with age through a process of ‘immune senescence’ Indeed, the responsiveness of T cells, which are known to be centrally involved in the immunopathogenesis of MS 88, appears to be particularly altered with age 87. Moreover, it is conceivable that the putative cytodegeneration involving the myelinating unit (oligodendroglia, their processes and myelin) in MS releases debris that is more antigenic 35,36,66 than the debris that is shed from the mainly synaptic and neuronal degeneration in Alzheimer’s disease and other traditional neurodegenerative disorders.

There is also evidences that people with MS has more chance to develop other autoimmune deseases. It’s hard to believe that a slow neurodegeneration would create acute inflammation in bowel or joints. The only one person with MS that I know personally had hashimoto’s thyroidis 5 years before the first symptom of MS.