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Copaxone interferes with the PrP Sc –GAG interaction
Author(s) -
Engelstein R.,
Ovadia H.,
Gabizon R.
Publication year - 2007
Publication title -
european journal of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 124
eISSN - 1468-1331
pISSN - 1351-5101
DOI - 10.1111/j.1468-1331.2007.01803.x
Subject(s) - chinese hamster ovary cell , scrapie , disease , hamster , pathogenesis , medicine , immune system , in vitro , mesocricetus , immunology , neurodegeneration , virology , slow virus , antibody , multiple sclerosis , prion protein , biology , receptor , progressive multifocal leukoencephalopathy , genetics
The hallmark of prion disease‐induced neurodegeneration is the accumulation of PrP Sc , a misfolded form of PrP C . In addition, several lines of evidence indicate a role for the immune system and, in particular, inflammation in prion disease pathogenesis. In this work, we tested whether Copaxone, an immunomodulatory agent currently used for the treatment of multiple sclerosis, can affect prion disease manifestation in scrapie‐infected hamsters. We show here that Copaxone exerted no effect on prion disease incubation time when treatment commenced 2 weeks after i.p. prion infection. However, when Copaxone was mixed with the initial prion inoculum or administered to hamsters weekly starting on the day of infection, prion disease incubation time was prolonged by 30 days. This suggests that Copaxone may affect the initial infection process. In vitro experiments indicate that Copaxone significantly reduced PrP Sc binding to both Chinese hamster ovary (CHO) cells and heparin beads and also binds to heparin by itself. Interestingly, Copaxone also abolished PrP Sc accumulation in scrapie‐infected cells. We propose that Copaxone delays prion infection by competing with the PrP Sc –glycosaminoglycans interaction. Whether the immunomodulating activity of Copaxone is related to its heparin binding and anti‐prion properties remains to be established.