Posted: Wed Sep 01, 2004 6:08 am
Thank you Finn for your posts, much more lucid than mine.
A couple of points. I agree with you that immunopathological studies shouldn't be the only way to investigate MS. But inflammation is pathognomonic in most neurodegenerative disease, albeit in MS as a secondary response to a primary pathogen (s).
For some time I have been looking at the role of brain chemistry in MS, along the lines that Harry mentions in his earlier post.
The reason I find the Lucchinetti argument persuasive is not because it sheds light on the cause (s) of MS but because through the identification of the various sub types in MS we may find better ways to treat the condition. More tailored to the individual’s disease pattern and less that of some one size fits all category.
It also fits with the idea that biochemical processes may be more important in some types of MS than in others. What if the reason the CRABS work effectively only in a minority of cases is because these are the cases with a more aggressive immune component?
Similarly, maybe antibiotics only work (I am not referring to minocycline neuro-protective benefits here) in the cases where MS has been caused by an infection such as described in other threads.
This may explain why in any MS cohort testing for a certain pathogen say, Chlamydia pneumoniae, not everyone will have antibodies to it, while one or two may have high levels.
So far these studies have been used to rule out pathogens but if we consider MS as a syndrome then it would less likely to find that in a random group of people with MS all have the same cause when testing for a pathogen.
I too usually go with Occam, but, in this case, I think MS could be a syndrome – many triggers and multiple factors. The primary link, an immune system reaction –dependent on the sub type and disease progression.
I think most MS researchers are concluding MS is not an auto-immune disease in the traditional sense and are more likely to classify it as neuro-degenerative. But the immune system is frustratingly complicated, for example, in Alzheimer’s they have identified over 40 different types of immune reaction going on. It just isn’t as simple as saying it is or it isn’t an immune disorder.
I think, whichever way you look at it, the immune system plays a role. Neurotransmitters govern the immune system. For example, Norepinephrine (adrenaline) helps downplay autoimmune reactions. Just out of interest the components of norepinephrine are the amino acids dl-phenylanine and Tyrosine (anyone remember the Loder regime which included phenylanine?).
Hormones are often neurochemicals – oestrogen, progesterone etc. All play a part in modifying the immune reaction. Does this mean a lack of these hormones or a hormonal imbalance could be the cause of MS? My instinct says no, but that they are more likely to play a role in modifying the condition though the immune system, but then again, maybe these are the causes for some people. And so it goes on.
It’s a bit chicken and egg –what comes first the immune reaction or the changes in biochemistry. If the immune reaction comes first caused by outside pathogens then this would also alter brain chemistry but if the brain chemistry altering the immune system comes first it could be because of many thousands of complex reasons. Hence back to the many causes argument.
I agree inflammation has been overplayed, it must be about getting the balance right – too much inflammation and you do get axonal damage (as a direct result of the inflammation not just as a bystander action), too little inflammation and if MS is cause by a pathogen then this too is damaging as the inflammation may well be protective.
I would love to believe MS has a single cause as it would make everything seem, at least, more hopeful, alas I think the lack of a single cause means there can be no simple therapies to prevent or treat MS.
Felly
A couple of points. I agree with you that immunopathological studies shouldn't be the only way to investigate MS. But inflammation is pathognomonic in most neurodegenerative disease, albeit in MS as a secondary response to a primary pathogen (s).
For some time I have been looking at the role of brain chemistry in MS, along the lines that Harry mentions in his earlier post.
The reason I find the Lucchinetti argument persuasive is not because it sheds light on the cause (s) of MS but because through the identification of the various sub types in MS we may find better ways to treat the condition. More tailored to the individual’s disease pattern and less that of some one size fits all category.
It also fits with the idea that biochemical processes may be more important in some types of MS than in others. What if the reason the CRABS work effectively only in a minority of cases is because these are the cases with a more aggressive immune component?
Similarly, maybe antibiotics only work (I am not referring to minocycline neuro-protective benefits here) in the cases where MS has been caused by an infection such as described in other threads.
This may explain why in any MS cohort testing for a certain pathogen say, Chlamydia pneumoniae, not everyone will have antibodies to it, while one or two may have high levels.
So far these studies have been used to rule out pathogens but if we consider MS as a syndrome then it would less likely to find that in a random group of people with MS all have the same cause when testing for a pathogen.
I too usually go with Occam, but, in this case, I think MS could be a syndrome – many triggers and multiple factors. The primary link, an immune system reaction –dependent on the sub type and disease progression.
I think most MS researchers are concluding MS is not an auto-immune disease in the traditional sense and are more likely to classify it as neuro-degenerative. But the immune system is frustratingly complicated, for example, in Alzheimer’s they have identified over 40 different types of immune reaction going on. It just isn’t as simple as saying it is or it isn’t an immune disorder.
I think, whichever way you look at it, the immune system plays a role. Neurotransmitters govern the immune system. For example, Norepinephrine (adrenaline) helps downplay autoimmune reactions. Just out of interest the components of norepinephrine are the amino acids dl-phenylanine and Tyrosine (anyone remember the Loder regime which included phenylanine?).
Hormones are often neurochemicals – oestrogen, progesterone etc. All play a part in modifying the immune reaction. Does this mean a lack of these hormones or a hormonal imbalance could be the cause of MS? My instinct says no, but that they are more likely to play a role in modifying the condition though the immune system, but then again, maybe these are the causes for some people. And so it goes on.
It’s a bit chicken and egg –what comes first the immune reaction or the changes in biochemistry. If the immune reaction comes first caused by outside pathogens then this would also alter brain chemistry but if the brain chemistry altering the immune system comes first it could be because of many thousands of complex reasons. Hence back to the many causes argument.
I agree inflammation has been overplayed, it must be about getting the balance right – too much inflammation and you do get axonal damage (as a direct result of the inflammation not just as a bystander action), too little inflammation and if MS is cause by a pathogen then this too is damaging as the inflammation may well be protective.
I would love to believe MS has a single cause as it would make everything seem, at least, more hopeful, alas I think the lack of a single cause means there can be no simple therapies to prevent or treat MS.
Felly