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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

Survival curves. Kaplan-Meier curves for GA (circles) and vehicle (boxes) treated animals. Log-rank test yielded a statistically significant difference in the survival curves (p < 0.05).
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Figure 1: Survival curves. Kaplan-Meier curves for GA (circles) and vehicle (boxes) treated animals. Log-rank test yielded a statistically significant difference in the survival curves (p < 0.05).

Mentions: Of the 68 infected animals 16 were killed on day 4 post-infection in order to study alterations in the early course of the disease. The remaining 52 animals entered the survival analysis. 37 of these mice developed signs of CM and were killed between day 5 and 9 post-infection when showing clinical signs of inevitable death (day 5, n = 6; day 6, n = 23; day 7, n = 3; day 8, n = 1; day 9, n = 4). The other 15 animals survived this critical period and were killed on day 11 post-infection. 15 animals (57.7%) in the treatment group developed CM compared to 22 animals (84.6%) in the control group. Kaplan Meier curves are shown in Figure 1. Log-rank test yielded a statistically significant lower risk for developing CM in the treatment group compared to the control group (p < 0.05).


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)

Survival curves. Kaplan-Meier curves for GA (circles) and vehicle (boxes) treated animals. Log-rank test yielded a statistically significant difference in the survival curves (p < 0.05).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 1: Survival curves. Kaplan-Meier curves for GA (circles) and vehicle (boxes) treated animals. Log-rank test yielded a statistically significant difference in the survival curves (p < 0.05).
Mentions: Of the 68 infected animals 16 were killed on day 4 post-infection in order to study alterations in the early course of the disease. The remaining 52 animals entered the survival analysis. 37 of these mice developed signs of CM and were killed between day 5 and 9 post-infection when showing clinical signs of inevitable death (day 5, n = 6; day 6, n = 23; day 7, n = 3; day 8, n = 1; day 9, n = 4). The other 15 animals survived this critical period and were killed on day 11 post-infection. 15 animals (57.7%) in the treatment group developed CM compared to 22 animals (84.6%) in the control group. Kaplan Meier curves are shown in Figure 1. Log-rank test yielded a statistically significant lower risk for developing CM in the treatment group compared to the control group (p < 0.05).

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