Glatiramer acetate reduces the risk for experimental cerebral malaria: a pilot study.
BACKGROUND
Cerebral malaria (CM) is associated with high mortality and morbidity caused by a high rate of transient or persistent neurological sequelae. Studies on immunomodulatory and neuroprotective drugs as ancillary treatment in murine CM indicate promising potential. The current study was conducted to evaluate the efficacy of glatiramer acetate (GA), an immunomodulatory drug approved for the treatment of relapsing remitting multiple sclerosis, in preventing the death of C57Bl/6J mice infected with Plasmodium berghei ANKA.


RESULTS
GA treatment led to a statistically significant lower risk for developing CM (57.7% versus 84.6%) in treated animals. The drug had no effect on the course of parasitaemia. The mechanism of action seems to be an immunomodulatory effect since lower IFN-gamma levels were observed in treated animals in the early course of the disease (day 4 post-infection) which also led to a lower number of brain sequestered leukocytes in treated animals. No direct neuro-protective effect such as an inhibition of apoptosis or reduction of micro-bleedings in the brain was found.


CONCLUSIONS
These findings support the important role of the host immune response in the pathophysiology of murine CM and might lead to the development of new adjunctive treatment strategies.
Lackner
Peter
P
Department of Neurology, Innsbruck Medical University, Innsbruck, Austria. peter.lackner@i-med.ac.at
Part
Andrea
A
Burger
Christoph
C
Dietmann
Anelia
A
Broessner
Gregor
G
Helbok
Raimund
R
Reindl
Markus
M
Schmutzhard
Erich
E
Beer
Ronny
R
D000818:Animals; D015153:Blotting, Western; D016207:Cytokines / Q000378:metabolism*; D000068717:Glatiramer Acetate; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D007274:Injections, Intraperitoneal; D053208:Kaplan-Meier Estimate; D016779:Malaria, Cerebral / Q000235:genetics / Q000276:immunology* / Q000401:mortality / Q000469:parasitology; D051379:Mice; D008810:Mice, Inbred C57BL; D010455:Peptides / Q000008:administration & dosage / Q000627:therapeutic use*; D010865:Pilot Projects; D010962:Plasmodium berghei / Q000276:immunology*; D012306:Risk
D016207:Cytokines; D007166:Immunosuppressive Agents; D010455:Peptides; D000068717:Glatiramer Acetate