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vessel with nuclei in blue,
protein skeletons in red,
and beta-catenin in green.
Image courtesy of
NYU Langone Medical Center
Drugs intended to treat high blood pressure might also be effective for treating cerebral malaria, according to preclinical research published in the Journal of Clinical Investigation.
Researchers tested these drugs—angiotensin II (Ang II) receptor modulators—in mice.
In an initial experiment, 2 of the drugs—losartan and CGP-42112A—reduced the incidence of cerebral malaria.
In another experiment, 2 other Ang II receptor modulators—irbesartan and compound 21 (C21)—were each combined with the antimalarial chloroquine.
Both combinations improved survival in mice with cerebral malaria when compared to chloroquine alone.
“About 1 in 5 patients with cerebral malaria die within 48 hours of being admitted to the hospital—the time it takes for the parasite-killing drug to take effect,” said study author Ana Rodriguez, PhD, of NYU Langone Medical Center in New York.
“If we could add a drug that stopped hemorrhages during that window, it would buy time and save lives.”
With this research, Dr Rodriguez and her colleagues showed that Ang II receptor modulators inhibit the activation of beta-catenin, a protein that plays a key role in cerebral malaria.
The team found that when Plasmodium falciparum–infected red blood cells rupture over human brain microvascular endothelial cells, this activates beta-catenin, which mediates the disruption of interendothelial junctions.
But inhibiting the activation of beta-catenin with Ang II receptor modulators protects endothelial cells from this disruption.
The researchers demonstrated this by infecting mice with P berghei ANKA, treating them with losartan or CGP-42112A, and monitoring them for neurological symptoms.
Seventy-five percent of control mice developed cerebral malaria, compared to 13.3% of mice treated with losartan and 28.5% treated with CGP-42112A.
In another experiment, the researchers treated malaria-infected mice with chloroquine, alone or in combination with irbesartan or C21, only after neurological signs were evident.
The team observed an increase in survival for mice treated with irbesartan or C21. The survival rate was 18% for the mice treated only with chloroquine, 65% for mice given irbesartan, and 73% percent for mice treated with C21.
The researchers also found that mice treated with irbesartan or C21 experienced fewer, smaller hemorrhages. And, in most cases, these mice fully recovered.
Dr Rodriguez and her colleagues said the next steps for this research will be to investigate the exact molecules coming from ruptured P falciparum–infected red blood cells that signal to beta-catenin in vessel walls, and to conduct trials that test the effects of Ang II receptor modulators in patients with cerebral malaria. 
vessel with nuclei in blue,
protein skeletons in red,
and beta-catenin in green.
Image courtesy of
NYU Langone Medical Center
Drugs intended to treat high blood pressure might also be effective for treating cerebral malaria, according to preclinical research published in the Journal of Clinical Investigation.
Researchers tested these drugs—angiotensin II (Ang II) receptor modulators—in mice.
In an initial experiment, 2 of the drugs—losartan and CGP-42112A—reduced the incidence of cerebral malaria.
In another experiment, 2 other Ang II receptor modulators—irbesartan and compound 21 (C21)—were each combined with the antimalarial chloroquine.
Both combinations improved survival in mice with cerebral malaria when compared to chloroquine alone.
“About 1 in 5 patients with cerebral malaria die within 48 hours of being admitted to the hospital—the time it takes for the parasite-killing drug to take effect,” said study author Ana Rodriguez, PhD, of NYU Langone Medical Center in New York.
“If we could add a drug that stopped hemorrhages during that window, it would buy time and save lives.”
With this research, Dr Rodriguez and her colleagues showed that Ang II receptor modulators inhibit the activation of beta-catenin, a protein that plays a key role in cerebral malaria.
The team found that when Plasmodium falciparum–infected red blood cells rupture over human brain microvascular endothelial cells, this activates beta-catenin, which mediates the disruption of interendothelial junctions.
But inhibiting the activation of beta-catenin with Ang II receptor modulators protects endothelial cells from this disruption.
The researchers demonstrated this by infecting mice with P berghei ANKA, treating them with losartan or CGP-42112A, and monitoring them for neurological symptoms.
Seventy-five percent of control mice developed cerebral malaria, compared to 13.3% of mice treated with losartan and 28.5% treated with CGP-42112A.
In another experiment, the researchers treated malaria-infected mice with chloroquine, alone or in combination with irbesartan or C21, only after neurological signs were evident.
The team observed an increase in survival for mice treated with irbesartan or C21. The survival rate was 18% for the mice treated only with chloroquine, 65% for mice given irbesartan, and 73% percent for mice treated with C21.
The researchers also found that mice treated with irbesartan or C21 experienced fewer, smaller hemorrhages. And, in most cases, these mice fully recovered.
Dr Rodriguez and her colleagues said the next steps for this research will be to investigate the exact molecules coming from ruptured P falciparum–infected red blood cells that signal to beta-catenin in vessel walls, and to conduct trials that test the effects of Ang II receptor modulators in patients with cerebral malaria.
vessel with nuclei in blue,
protein skeletons in red,
and beta-catenin in green.
Image courtesy of
NYU Langone Medical Center
Drugs intended to treat high blood pressure might also be effective for treating cerebral malaria, according to preclinical research published in the Journal of Clinical Investigation.
Researchers tested these drugs—angiotensin II (Ang II) receptor modulators—in mice.
In an initial experiment, 2 of the drugs—losartan and CGP-42112A—reduced the incidence of cerebral malaria.
In another experiment, 2 other Ang II receptor modulators—irbesartan and compound 21 (C21)—were each combined with the antimalarial chloroquine.
Both combinations improved survival in mice with cerebral malaria when compared to chloroquine alone.
“About 1 in 5 patients with cerebral malaria die within 48 hours of being admitted to the hospital—the time it takes for the parasite-killing drug to take effect,” said study author Ana Rodriguez, PhD, of NYU Langone Medical Center in New York.
“If we could add a drug that stopped hemorrhages during that window, it would buy time and save lives.”
With this research, Dr Rodriguez and her colleagues showed that Ang II receptor modulators inhibit the activation of beta-catenin, a protein that plays a key role in cerebral malaria.
The team found that when Plasmodium falciparum–infected red blood cells rupture over human brain microvascular endothelial cells, this activates beta-catenin, which mediates the disruption of interendothelial junctions.
But inhibiting the activation of beta-catenin with Ang II receptor modulators protects endothelial cells from this disruption.
The researchers demonstrated this by infecting mice with P berghei ANKA, treating them with losartan or CGP-42112A, and monitoring them for neurological symptoms.
Seventy-five percent of control mice developed cerebral malaria, compared to 13.3% of mice treated with losartan and 28.5% treated with CGP-42112A.
In another experiment, the researchers treated malaria-infected mice with chloroquine, alone or in combination with irbesartan or C21, only after neurological signs were evident.
The team observed an increase in survival for mice treated with irbesartan or C21. The survival rate was 18% for the mice treated only with chloroquine, 65% for mice given irbesartan, and 73% percent for mice treated with C21.
The researchers also found that mice treated with irbesartan or C21 experienced fewer, smaller hemorrhages. And, in most cases, these mice fully recovered.
Dr Rodriguez and her colleagues said the next steps for this research will be to investigate the exact molecules coming from ruptured P falciparum–infected red blood cells that signal to beta-catenin in vessel walls, and to conduct trials that test the effects of Ang II receptor modulators in patients with cerebral malaria.