My thought on the efficacy of antibiotics is that the pathogen is stimulating a heat shock-type/stress response in the cells. When a pathogen invades a cell or tissue, the pathogen tries to set up its optimal conditions: altering the pH, changing the ionic milieu, taking over transcription machinery (polymerases), and translation machinery (ribosomes). The pathogen will replicate or go into a latent phase to replicate at a later date. The cell, on the other hand, responds with a stress response: releasing chaperone proteins to try to refold disrupted proteins, ubiquitinating proteins to mark them for degradation if they are beyond salvage, methylating DNA in the hopes of silencing foreign genes and, if all else fails, going into apoptosis to protect its neighbors. Normally these episodes of invasion and stress response resolve themselves in MSers and non-MSers. However, it is my belief that, in a very few cells, due to some earlier chromosome damage, epigenetic control has been compromised so that the cell overexpresses some of its genes. When the cell attempts a stress response, it overreacts and hampers its normal functioning, which could be myelin formation. So, the antibiotics remove the bacteria and therefore the cells are not stressed into overreacting.
That's pretty vague mumbo-jumbo. So I will give you the details that I have in mind. Of course I needn't remind you that this is only hypothesis on my part.
The polyamines are small, positively charged molecules that have many interactions in cells. They are essential for growth and proliferation. Their size, length, and charge distribution give the potential for many unique interactions, particularly with the negatively charged DNA, RNA, and phospholipids (some of which are in myelin). Their unique characteristics can also make them competitors with histones that package genes, and with specialized proteins like MBP. The main polyamines in cells are: putrescine (+2, about 8 angstroms long, also called a diamine, +NCCCCN+), spermidine (+3, 10-14 angstroms, +NCCCCN+CCCN+), and spermine (+4, 14-20 angstroms, +NCCCN+CCCCN+CCCN+). Normally, prokaryotes (bacteria) express putrescine and spermidine. They do not use spermine. Eukaryotes (mammals and such) use spermidine and spermine, and only transiently have putrescine around. Polyamine levels are tightly controlled because of their potential interactions. They are elevated in many cancers. They are the target of much research since inhibiting them may reduce tumor growth.
Putrescine is used to make spermidine by the enzyme spermidine synthase. Spermidine is used to make spermine by spermine synthase. Some of the polyamine genes are considered to be heat shock genes in that they are induced when a cell is stressed. So bacteria are secreting putrescine and spermidine to control their ionic environment and the cell goes into a stress response. Usually polyamines are bound to something (DNA, RNA, phospholipids) but now from the cell and the bacteria there is an increase in
free polyamines. What if there were overexpression of spermine synthase in a few cells due to chromosome damage? (I can present a very strong case for this but maybe in another post when I have more time to write.) The putrescine and spermidine could be converted to spermine, causing an imbalance in the spermidine/spermine ratio. How important is this? You have probably never heard of the quaking or jimpy mouse strains but they are probably the best models for MS. They both have progressive neurodegeneration from early in life. This has been attributed to an altered spermidine/spermine ratio compared to controls (ie. more spermine, less spermidine). Look at: Russell DH, Meier H. Alterations in the accumulation patterns of polyamines in brains of myelin-deficient mice. J Neurobiol 1975; 6:267-274. Spermidine appears to be an important component of myelin. Giorgi PP. Spermidine: a constituent of the myelin sheath? Neurosci Lett 1978; 10:355-340. Recently, a research group in California reported that they were finding myelin in lesions had alterations in the overall charge, more positive than normal. Sorry I don't have that news item handy but I will post it if I can find it. My thought is that spermine may be substituting for spermidine since there is an abundance in spermine relative to spermidine in the cells with chromosome damage. This could also interfere with the normal assembly of myelin and the role of MBP. There are some other consequences of polyamines I will list by giving you some references. Koenig H, Goldstone AD, Lu CY. Blood-brain barrier breakdown in cold-injured brain is linked to a biphase stimulation of ornithine decarboxylase activity and polyamine synthesis: both are coordinately inhibited by verapamil, dexamethasone, and aspirin. J Neurochem 1989; 52:101-109. Scott RH, Sutton KG, Dolphin AC. Interactions of polyamines with neuronal ion channels. Trends Neurosci 1993; 16:1502-1510. Williams K. Modulation and block of ion channels: a new biology of polyamines. Cell Signal 1997; 9:1-13.
Don't go trying to self-medicate based on anything I've written here! Remember it is just hypothesis and could be wrong. It certainly is not easy to test. Isn't it interesting that I didn't mention autoimmunity or genetics? The chromosome damage I am thinking about would not occur at a specific spot in a specific gene everytime and the autoimmune reaction is something that occurs later if at all.
This is only part of a hypothesis I've been developing for a number of years on the so-called autoimmune diseases. A few years ago I published an article called 'Autoimmune diseases are antigen-driven, epigenetic diseases' in Medical Hypotheses. That was a cruder version of the hypothesis. I recently published an article 'Autoimmune disorders result from loss of epigenetic control following chromosome damage' in the online version of Medical Hypotheses. Unfortunately, even though I wrote it and paid to have it published, I can not see it or link you to it because neither I nor my institution have subscriptions. I have asked for permission to post or link to the article but the journal hasn't responded yet. I have a pdf file but copyright restrictions prevent me from just sending it out. No matter. I am writing a longer version and recreating the figures so I can post it on ThisIsMS. I have been writing the longer version but we have been dodging hurricanes, having a house remodeled, and moving all this summer so it has been difficult to finish writing. Once I get the article posted on ThisIsMS or if you can reach it on Medical Hypotheses, I would appreciate any feedback, critiques, X prizes, etc.
Sorry about the length of this post but it is not an easy disease or hypothesis to discuss in brief is it?