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Glatiramer acetate reduces the risk for experimental cerebral malaria: a pilot study.

Lackner P, Part A, Burger C, Dietmann A, Broessner G, Helbok R, Reindl M, Schmutzhard E, Beer R - Malar. J. (2009)

Bottom Line: 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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Neurology, Innsbruck Medical University, Innsbruck, Austria. peter.lackner@i-med.ac.at

ABSTRACT

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.

Methods and 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.

Conclusion: 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.

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Related in: MedlinePlus

Clinical course of the disease and parasitaemia levels. A: Cumulative SHIRPA score of GA (open bars) and vehicle (filled bars) treated animals on day 0, 5, 11 post-infection and in moribund animals with CM. B: Course of parasitaemia of GA (open bars) and vehicle (filled bars) treated animals. No significant differences were found in the respective values of the SHIRPA score and parasitaemia between GA and vehicle treated animals. Mean values and SEM are shown.
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Figure 2: Clinical course of the disease and parasitaemia levels. A: Cumulative SHIRPA score of GA (open bars) and vehicle (filled bars) treated animals on day 0, 5, 11 post-infection and in moribund animals with CM. B: Course of parasitaemia of GA (open bars) and vehicle (filled bars) treated animals. No significant differences were found in the respective values of the SHIRPA score and parasitaemia between GA and vehicle treated animals. Mean values and SEM are shown.

Mentions: In order to assess putative differences in the clinical course of the disease, the SHIRPA score was performed on baseline, day 5, in moribund CM animals and on day 11 post-infection in animals which did not develop CM (NCM group). No significant differences were found in the respective values of the SHIRPA score between GA and vehicle treated animals (Figure 2A). There was a trend towards a higher/better SHIRPA score in GA treated NCM animals on day 11 post-infection (p = 0.056; Figure 2A). Parasitaemia levels were also compared and did not yield significant differences (Figure 2B).


Glatiramer acetate reduces the risk for experimental cerebral malaria: a pilot study.

Lackner P, Part A, Burger C, Dietmann A, Broessner G, Helbok R, Reindl M, Schmutzhard E, Beer R - Malar. J. (2009)

Clinical course of the disease and parasitaemia levels. A: Cumulative SHIRPA score of GA (open bars) and vehicle (filled bars) treated animals on day 0, 5, 11 post-infection and in moribund animals with CM. B: Course of parasitaemia of GA (open bars) and vehicle (filled bars) treated animals. No significant differences were found in the respective values of the SHIRPA score and parasitaemia between GA and vehicle treated animals. Mean values and SEM are shown.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2651188&req=5

Figure 2: Clinical course of the disease and parasitaemia levels. A: Cumulative SHIRPA score of GA (open bars) and vehicle (filled bars) treated animals on day 0, 5, 11 post-infection and in moribund animals with CM. B: Course of parasitaemia of GA (open bars) and vehicle (filled bars) treated animals. No significant differences were found in the respective values of the SHIRPA score and parasitaemia between GA and vehicle treated animals. Mean values and SEM are shown.
Mentions: In order to assess putative differences in the clinical course of the disease, the SHIRPA score was performed on baseline, day 5, in moribund CM animals and on day 11 post-infection in animals which did not develop CM (NCM group). No significant differences were found in the respective values of the SHIRPA score between GA and vehicle treated animals (Figure 2A). There was a trend towards a higher/better SHIRPA score in GA treated NCM animals on day 11 post-infection (p = 0.056; Figure 2A). Parasitaemia levels were also compared and did not yield significant differences (Figure 2B).

Bottom Line: 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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Neurology, Innsbruck Medical University, Innsbruck, Austria. peter.lackner@i-med.ac.at

ABSTRACT

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.

Methods and 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.

Conclusion: 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.

Show MeSH
Related in: MedlinePlus