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Table 1
Studies describing the use of EPO and its derivatives in EAE models in rat and mouse
MBP-EAE (rat)
MOG-EAE (rat)
MOG-EAE (mouse)
PLP-EAE (mouse)
Erythropoietin (EPO)
(
3
)
(
8
)
(
10
)
(
16
)
(
7
)
(
9
)
(
21
)
(
18
)
(
22
)
(
23
)
Carbamylated EPO (CEPO)
(
20
)
(
21
)
AsialoEPO
(
21
)
Darbepoetin alfa
(
24
)
The observation that erythropoietin (EPO) is neuroprotective
and, more importantly, when administered systemically reaches the
brain in high enough amounts to protect from brain injury opened
new therapeutic possibilities for neurodegenerative diseases.
Interestingly, EPO had a striking blocking effect on the
neuroinflammation associated with brain injury, suggesting that it
might be effective in diseases with a substantial neuroinflammatory
component, like MS (
3
).
Since then, preclinical studies have reported efficacy of sys-
temically administered EPO, and EPO derivatives devoid of eryth-
ropoietic activity, in several models of experimental autoimmune
encephalomyelitis (EAE), the experimental model of MS (reviewed
in (
4, 5
)). Overall, these studies have shown that EPO ameliorates
the clinical course of EAE targeting not only inflammation but
also demyelination and axonal damage, and inducing neurogenesis
and oligodendrogenesis, suggesting that it might be an effective
neuroregenerative therapy. Accordingly, in a pilot clinical trial
EPO improved cognitive functions in patients with chronic pro-
gressive MS (
6
).
Results obtained with several schedules of EPO treatment in
different models of EAE are reviewed here (Table
1
), together with
a specific example of efficacy of EPO and of a non-erythropoietic
EPO derivative, carbamylated EPO (CEPO), in myelin oligoden-
drocyte glycoprotein (MOG)-induced EAE, a widely used model
of chronic progressive EAE in mice.
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