EP is a community where members connect through shared life experiences-- like MS--and so much more. You are not defined by any one thing, so be your true self and find others just like you at
Experience Project.
dignan,
thanks for sharing the abstract with the rest of us. I found its subject very interesting. By coincidence, a dear friend of mine sent me the full article of the same study few days ago, and thus gave me a good reason to visit this thread again.
dignan wrote:
I think this abstract sounds interesting, although it would be more interesting if we could read the whole article...
Well, basicly the abstract says it all. According to the researchers metabolic dysfunction in oligodendrocytes might be able to cause both axonal degeneration and focal inflammation. If that was the case, oligodendrocyte apoptosis and axonal degeneration would be the primary processes in MS, and inflammation would cause only "collateral damage".
Anyway, here's a short quote from the article:
Conclusion
Recent findings have initiated a possible shift of paradigms, with inflammatory demyelination not only being caused by ‘primary’ immune defects, which is of obvious relevance to MS. Investigating the driving force behind inflammatory changes in the white matter, making use of novel mouse models with a primary defect in glial cell function and metabolism, will be a necessary next step. It is possible that an entire spectrum of inflammatory demyelinating diseases exist, in which multifocal white matter lesions (including classical MS lesions) reveal a final common pathway in brain pathology and the intrinsic susceptibility of oligodendrocytes to stimulate a local immune response. Alterations of lipid metabolism may play a key role.
Be well.
-finn _________________ "You get to an age where what you might be gives way to what you have been. You weren't Einstein. You weren't anything. That's a bad moment."
Finn, thanks for the update. It feels like these researchers could be on to something. It just seems more likely that something is actually causing inflamation and not that the inflamatory mechanisms are malfunctioning. That's just my uninformed opinion though.
The UK MS Society website has an article by Professor Alan Thompson about the last 10 years and MS (you can listen to Prof Thompson or read the transcript). One of the interesting bits from the article was:
Quote:
"We have begun to understand how axons (nerve fibres) may be
damaged in MS, which is very important because disability and
progression in MS are thought to be associated with the loss of
axons. Scientists have been able to appreciate the extent of ‘diffuse’
or more generalised damage to nerve fibres in the central nervous
system in people who have MS. This is damage that extends beyond
the MS scars or lesions to areas of the brain that had appeared
unaffected."
So there is now a recognition that the focal inflammation (the inflammatory lesions that can be seen by MRI) is only part of the puzzle. The same website also includes some interviews with the researchers who presented at the MS Life conference. One of the interviews is with Dr Coles who, at the end of his interview, says that oligodendrocytes must be protected (in addition to stopping the immune attack and having neuro-protective agents). I suppose the next step is for the researchers to work out what is happening to the oligodendrocytes in MS brains and what is causing it.
We question whether inflammatory demyelination is primary or secondary in the disease process
The other author, Nave, was an author of the abstract/article mentioned earlier in the thread hypothesizing that dysfunctions in oligodendrocytes might trigger the inflammatory response.
One of these days we just might know what kind of disease MS actually is.
Sharon, that's uncanny, I was just looking at that abstract and thinking about this thread too! I was hoping I could dig up the actual article, but it's not freely available. Perhaps somebody with access can give us the low-down...
I don't think the authors are saying much that's new, but I find their explanation to be accessible.
Multiple sclerosis: a degenerative disease?
Article in French
Bull Acad Natl Med. 2008 Mar;192(3)
Confavreux C, Vukusic S.
Service de Neurologie A et Centre de Coordination EDMUS sur la sclérose en plaques, INSERM Unité 842, Hospices Civils de Lyon, Université Lyon 1, Hôpital Neurologique Pierre Wertheimer, 59 boulevard Pinel, 69677 Lyon-Bron. christian.confavreux@chu-lyon.fr
Multiple sclerosis (MS) is an organ-specific autoimmune disease targeting central nervous system myelin. The clinical course results from an interplay between relapses and progression. Relapses are the clinical counterpart of acute focal inflammation of the central nervous system, whereas progression is due to chronic diffuse neurodegeneration. According to the autoimmune theory, successive clinical and especially subclinical relapses eventually lead to irreversible disability, while the accumulation of focal lesions explains the diffuse neurodegeneration.
Things are not that simple, however. Relapses are not the main contributor to irreversible disability, as shown both in individual patients and at the population level. Likewise, MRI studies show that focal lesions are not entirely responsible for the diffuse neurodegeneration. Relapse prevention with disease-modifying drugs does not markedly influence the onset of irreversible disability or the progression of cerebral atrophy. In fact, acute inflammatory focal lesions and relapses may be the "tree that hides the forest".
Indeed, clinical progression and chronic diffuse neurodegeneration both play a key role, developing independently of relapses and focal lesions. Should MS therefore be considered a primary degenerative disorder rather than a primary autoimmune disease?
Not yet: recent pathological studies clearly demonstrate the presence of disseminated activated microglial-like inflammatory cells in the central nervous system. These could lead to a deleterious inflammatory process, even if not specifically autoimmune, unlike the inflammation occurring in acute lesions. If this pathogenetic picture of the disease is correct, then it has implications for therapeutic strategies. Indeed, treating the acute focal inflammation, as we successfully do nowadays, will not be enough. It will also be necessary to extinguish the slow-burning diffuse inflammation nested in the central nervous system behind the blood-brain barrier. This is the new therapeutic challenge in MS.
Joined: May 04, 2006 Posts: 3371 Location: Mid-Michigan
Posted: Sat Oct 04, 2008 8:11 pm Post subject:
dignan wrote:
It will also be necessary to extinguish the slow-burning diffuse inflammation nested in the central nervous system behind the blood-brain barrier. This is the new therapeutic challenge in MS.
Wow, I couldn't agree more! I wish I could read French!
I've tried and I don't think I can get that article anyway, and as a matter of fact I've been having an awful time getting pubmed to work lately.
Bob _________________ Wife diagnosed with MS in Feb. 2006 and is a participant in the Tovaxin IIb clinical trial.
All times are GMT - 6 Hours Goto page Previous1, 2, 3 ... 16, 17, 18
Page 18 of 18
You cannot post new topics in this forum You cannot reply to topics in this forum You cannot edit your posts in this forum You cannot delete your posts in this forum You cannot vote in polls in this forum
Forum FAQ
Search
Usergroups
Profile
Log in to check your private messages
Log in
