Brainteaser wrote:So if this is true, they should be able to do drug/other testing on mice infected with PPMS-CSF to help solve the PPMS dilemma?
1eye wrote:I guess this is how it's going to be. People claiming to have licked the thing at least in mice, other people claiming to have found a cause in mice with interleukin 1-beta and p53. Lots of mouse models, lots of bad guys, but no silver bullets. No treatments in my lifetime. Well, it's officially shorter by a year, as of yesterday, anyway. I didn't expect to be any better at this age.
Multiple sclerosis (MS) is an autoimmune disease characterized by inflammatory demyelination and neurodegeneration throughout the CNS, which lead over time to a condition of irreversible functional decline known as progressive MS. Currently, there are no satisfactory treatments for this condition because the mechanisms that underlie
disease progression are not well understood. This is partly due to the lack of a specific animal model that represents
progressive MS. We investigated the effects of intracerebroventricular injections of cerebrospinal fluid (CSF)
derived from untreated primary progressive (PPMS), secondary progressive (SPMS), and relapsing/remitting
(RRMS) MS patients into mice. We found discrete inflammatory demyelinating lesions containing macrophages,
B cell and T cell infiltrates in the brains of animals injected with CSF from patients with progressive MS. These
lesions were rarely found in animals injected with RRMS-CSF and never in those treated with control-CSF. Animals
that developed brain lesions also presented extensive inflammation in their spinal cord. However, discrete spinal
cord lesions were rare and only seen in animals injected with PPMS-CSF. Axonal loss and astrogliosis were seen
within the lesions following the initial demyelination. In addition, Th17 cell activity was enhanced in the CNS
and in lymph nodes of progressive MS-CSF injected animals compared to controls. Furthermore, CSF derived
from MS patients who were clinically stable following therapy had greatly diminished capacity to induce CNS
lesions in mice. Finally,we provided evidence suggesting that differential expression of pro-inflammatory cytokines
present in the progressive MS CSF might be involved in the observed mouse pathology. Our data suggests that the
agent(s) responsible for the demyelination and neurodegeneration characteristic of progressive MS is present in
patient CSF and is amenable to further characterization in experimental models of the disease.
Demyelination precedes axonal loss and glial scar formation.
Progressive MS-CSF treatments altered the expression of immune-system
related genes in the mouse CNS.
.Progressive MS-CSF treatments enhanced Th17 cell activity in the mouse
CNS and in its periphery
.CSF-induced brain lesions are drastically reduced by clinical treatment and
correlate with patient CSF levels of pro-inflammatory cytokines
David1949 wrote:There is something else here that might be muddying up their results. From table 1 of the PDF file
you can see that the RR patients had an average disease duration of only 2.5 years. That is much less than the 13.83 years for the PPMS patients and the 21.7 years for SPMS patients. Further, the average EDSS score for the RRMS patients was only 0.88 vs 6.6 and 7.5 for the PPMS and SPMS groups respectively. So the RRMS group had the disease for much less time and had suffered much less disability. That may also be a factor in the results they obtained.
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