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infecting an RBC
Image courtesy of St. Jude
Children’s Research Hospital
Luminol, the compound detectives spray at crime scenes to find trace amounts of blood, can help kill malaria parasites, according to preclinical research published in eLife.
Luminol glows blue when it encounters the hemoglobin in red blood cells (RBCs), and researchers have found they can trick malaria-infected RBCs into
building up a volatile chemical stockpile that can be set off by luminol’s glow.
To achieve this, the researchers exposed infected RBCs to an amino acid known as 5-aminolevulinic acid (ALA), luminol, and 4-iodophenol (a small-molecule that enhances the intensity and duration of luminol chemiluminescence).
This triggered buildup of the chemical, protoporphyrin IX (PPIX), which effectively killed the parasites. When the team substituted artemisinin for 4-iodophenol, they observed similar results.
“The light that luminol emits is enhanced by the antimalarial drug artemisinin,” said study author Daniel Goldberg, MD, PhD, of the Washington University School of Medicine in St Louis, Missouri.
“We think these agents could be combined to form an innovative treatment for malaria.”
The researchers believe this type of therapy would have an advantage over current malaria treatments, which have become less effective as the parasite mutates. That is because the new approach targets proteins made by human RBCs, which the parasite can’t mutate.
To uncover this approach, Dr Goldberg and his colleagues worked with human RBCs infected with Plasmodium falciparum. The team wanted to better understand how the parasite gets hold of heme, which is essential to the parasite’s survival.
They found that P falciparum opens an unnatural channel on the surface of RBCs. When the researchers put ALA (an ingredient of heme) into a solution containing infected RBCs, ALA entered the cells through the channel and started the heme-making process.
This led to a buildup of PPIX. When exposed to luminol and 4-iodophenol, PPIX emitted free radicals. This potently inhibited parasite growth, according to the researchers. And microscopic examination revealed widespread parasite death.
The ALA/luminol/4-iodophenol combination also worked in a parasite line that was resistant to antifolate and quinolone antibiotics, as well as one with a kelch-13 protein mutation, which confers artemisinin tolerance.
The researchers then wanted to determine if artemisinin would enhance their strategy. So they incubated malaria-infected RBCs with ALA, luminol, and/or sub-therapeutic doses of dihydroartemisinin.
Each of the components alone or 2 of them together had little effect, but all 3 in combination successfully ablated parasite growth.
The researchers are now planning to test this treatment approach in vivo.
“All of these agents—the amino acid, the luminol, and artemisinin—have been cleared for use in humans individually, so we are optimistic that they won’t present any safety problems together,” Dr Goldberg said. “This could be a promising new treatment for a devastating disease.” 
infecting an RBC
Image courtesy of St. Jude
Children’s Research Hospital
Luminol, the compound detectives spray at crime scenes to find trace amounts of blood, can help kill malaria parasites, according to preclinical research published in eLife.
Luminol glows blue when it encounters the hemoglobin in red blood cells (RBCs), and researchers have found they can trick malaria-infected RBCs into
building up a volatile chemical stockpile that can be set off by luminol’s glow.
To achieve this, the researchers exposed infected RBCs to an amino acid known as 5-aminolevulinic acid (ALA), luminol, and 4-iodophenol (a small-molecule that enhances the intensity and duration of luminol chemiluminescence).
This triggered buildup of the chemical, protoporphyrin IX (PPIX), which effectively killed the parasites. When the team substituted artemisinin for 4-iodophenol, they observed similar results.
“The light that luminol emits is enhanced by the antimalarial drug artemisinin,” said study author Daniel Goldberg, MD, PhD, of the Washington University School of Medicine in St Louis, Missouri.
“We think these agents could be combined to form an innovative treatment for malaria.”
The researchers believe this type of therapy would have an advantage over current malaria treatments, which have become less effective as the parasite mutates. That is because the new approach targets proteins made by human RBCs, which the parasite can’t mutate.
To uncover this approach, Dr Goldberg and his colleagues worked with human RBCs infected with Plasmodium falciparum. The team wanted to better understand how the parasite gets hold of heme, which is essential to the parasite’s survival.
They found that P falciparum opens an unnatural channel on the surface of RBCs. When the researchers put ALA (an ingredient of heme) into a solution containing infected RBCs, ALA entered the cells through the channel and started the heme-making process.
This led to a buildup of PPIX. When exposed to luminol and 4-iodophenol, PPIX emitted free radicals. This potently inhibited parasite growth, according to the researchers. And microscopic examination revealed widespread parasite death.
The ALA/luminol/4-iodophenol combination also worked in a parasite line that was resistant to antifolate and quinolone antibiotics, as well as one with a kelch-13 protein mutation, which confers artemisinin tolerance.
The researchers then wanted to determine if artemisinin would enhance their strategy. So they incubated malaria-infected RBCs with ALA, luminol, and/or sub-therapeutic doses of dihydroartemisinin.
Each of the components alone or 2 of them together had little effect, but all 3 in combination successfully ablated parasite growth.
The researchers are now planning to test this treatment approach in vivo.
“All of these agents—the amino acid, the luminol, and artemisinin—have been cleared for use in humans individually, so we are optimistic that they won’t present any safety problems together,” Dr Goldberg said. “This could be a promising new treatment for a devastating disease.”
infecting an RBC
Image courtesy of St. Jude
Children’s Research Hospital
Luminol, the compound detectives spray at crime scenes to find trace amounts of blood, can help kill malaria parasites, according to preclinical research published in eLife.
Luminol glows blue when it encounters the hemoglobin in red blood cells (RBCs), and researchers have found they can trick malaria-infected RBCs into
building up a volatile chemical stockpile that can be set off by luminol’s glow.
To achieve this, the researchers exposed infected RBCs to an amino acid known as 5-aminolevulinic acid (ALA), luminol, and 4-iodophenol (a small-molecule that enhances the intensity and duration of luminol chemiluminescence).
This triggered buildup of the chemical, protoporphyrin IX (PPIX), which effectively killed the parasites. When the team substituted artemisinin for 4-iodophenol, they observed similar results.
“The light that luminol emits is enhanced by the antimalarial drug artemisinin,” said study author Daniel Goldberg, MD, PhD, of the Washington University School of Medicine in St Louis, Missouri.
“We think these agents could be combined to form an innovative treatment for malaria.”
The researchers believe this type of therapy would have an advantage over current malaria treatments, which have become less effective as the parasite mutates. That is because the new approach targets proteins made by human RBCs, which the parasite can’t mutate.
To uncover this approach, Dr Goldberg and his colleagues worked with human RBCs infected with Plasmodium falciparum. The team wanted to better understand how the parasite gets hold of heme, which is essential to the parasite’s survival.
They found that P falciparum opens an unnatural channel on the surface of RBCs. When the researchers put ALA (an ingredient of heme) into a solution containing infected RBCs, ALA entered the cells through the channel and started the heme-making process.
This led to a buildup of PPIX. When exposed to luminol and 4-iodophenol, PPIX emitted free radicals. This potently inhibited parasite growth, according to the researchers. And microscopic examination revealed widespread parasite death.
The ALA/luminol/4-iodophenol combination also worked in a parasite line that was resistant to antifolate and quinolone antibiotics, as well as one with a kelch-13 protein mutation, which confers artemisinin tolerance.
The researchers then wanted to determine if artemisinin would enhance their strategy. So they incubated malaria-infected RBCs with ALA, luminol, and/or sub-therapeutic doses of dihydroartemisinin.
Each of the components alone or 2 of them together had little effect, but all 3 in combination successfully ablated parasite growth.
The researchers are now planning to test this treatment approach in vivo.
“All of these agents—the amino acid, the luminol, and artemisinin—have been cleared for use in humans individually, so we are optimistic that they won’t present any safety problems together,” Dr Goldberg said. “This could be a promising new treatment for a devastating disease.”