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Monday, November 29, 2010 9:46 PM
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Ken Torbert
It is amazing how many articles are published every month
in high-ranking journals on the pathogenesis and treatment
of multiple sclerosis (MS). This month’s Journal Club will
focus on three recent publications. The first deals with
immune regulation of MS by transdermally applied myelin
peptides, which seems to be a very elegant new approach
for the treatment of MS. If the findings of this primarily
histological study can be confirmed in placebo-controlled
randomized clinical trials, this would be a major breakthrough
for the treatment of MS. The second article deals
with the levels of myxovirus resistance protein A mRNA,
which is induced by type I interferons, i.e., interferon-a and
interferon-b. In 116 untreated patients, the authors demonstrated
that low levels of myxovirus resistance protein A
mRNA were associated with a high risk of relapses and
contrast-enhancing lesions. If these data can be confirmed,
the level of myxovirus resistance protein A mRNA can be a
biomarker for clinical disease activity in MS. The third
article in this month’s Journal Club focuses on CSF ferritin
levels in patients with MS. This work is closely related to
the proposed hypothesis of chronic cerebrospinal venous
insufficiency as a cause of MS. The authors did not find
significantly increased ferritin levels in MS and there was
no significant change in CSF ferritin levels over a 3-year
follow-up period. Therefore, this article and several studies
that have been published since the above-mentioned
hypothesis was proposed in 2006 do not support an etiological
role of chronic cerebrospinal venous insufficiency.
Immune regulation of MS by transdermally applied
myelin peptides
Rituximab, alemtuzumab, cladribine, natalizumab, and
fingolimod, which have been recently tested in several
clinical trials on MS, all inhibit immune function, thereby
reducing inflammation inside the brain. An elegant alternative
way to treat MS is the induction of a specific immune
tolerance, as suggested more than 150 years ago by Paul
Ehrlich. Several attempts have already been made to apply
such an antigen-specific therapy in patients with MS. For
instance, oral myelin proteins, altered peptide ligands, and
intravenous myelin basic protein have all been tested in
patients with MS in clinical trials, but showed no or only a
modest effect on the course of the disease (for references,
see Juryn´czyk M et al 2010). An alternative route for the
application of these specific antigens is transdermally,
which has been proven to be efficient in animal models of
MS such as experimental autoimmune encephalomyelitis.
Maciej Juryn´czyk and co-workers from Lodz and
Krakow in Poland used such an approach in 30 patients
with relapsing–remitting MS. They applied a mixture of
three myelin peptides transdermally: MBP85-99, PLP139-
151, and MOG35-55 versus placebo. The patch with the
different antigens was changed once a week for 4 weeks
and then once a month for 11 months. The follow-up
period was 1 year. The phenotype of immune cells in the
skin was assessed by immunohistochemistry. The authors
also analyzed cell populations in lymph nodes by flow
cytometry as well as cytokine production and myelinspecific
proliferation.
The major findings of this study were as follows: (1) the
myelin peptides that were applied transdermally activated
dendritic Langerhans cells in the skin; (2) they induced a
unique population of granular dendritic cells in local lymph
M. Strupp (&)
Department of Neurology and IFBLMU, University Hospital
http://www.springerlink.com/content/h23t247003741267/
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