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falciparum
in a mouse liverImage courtesy of Seattle
Biomedical Research Institute
A new compound can fight multidrug-resistant malaria, according to preclinical research published in Science Translational Medicine.
The compound, DSM265, targets DHODH, an enzyme involved in the malaria parasite’s production of nucleotides.
Experiments showed that DSM265 can target the parasite at both the blood and liver stages of infection. And the compound appeared to be safe.
Based on these results, DSM265 has advanced to clinical trials.
Investigators believe the drug could potentially be partnered with other antimalarials for a single-dose treatment or once-weekly prophylaxis.
“This is the first of a new class of molecules that’s going into humans,” said study author Pradipsinh Rathod, PhD, of the University of Washington in Seattle.
“Until now, everything else in humans has been variations of drugs that have been developed in the distant past.”
The investigators tested DSM265 in multiple models, including human cells, rodents, dogs, and monkeys.
DSM265 arrested growth of the Plasmodium falciparum parasite at both the blood and liver stages. And the drug was active against P falciparum strains that were resistant to chloroquine and pyrimethamine.
DSM265 also proved to be long-acting. Experiments suggested a dose of 200 mg to 400 mg would maintain therapeutic concentrations in humans for at least 8 days.
Repeated doses of DSM265, given to mice and dogs, did not cause major side effects. The researchers said DSM265 was well tolerated at all dose levels given to mice (25 to 200 mg/kg per day once daily for 7 days) and dogs (30 to 480 mg/kg every other day for 10 days).
None of the animals died, and there were no clinical effects observed in the mice. Dogs receiving the highest dose of DSM265 experienced vomiting, apparent loss of appetite, and a slight increase in bilirubin that was not accompanied by changes in any other liver function markers.
Dr Rathod said he hopes the development and discovery pipeline for DSM265 will pave the way for a faster and more collaborative drug development process in “the long war against malaria.”
In an attempt to accelerate the drug’s development, the investigators transferred their patent rights for DSM265 to the Medicines for Malaria Venture, a Bill & Melinda Gates Foundation-supported nonprofit that is leading some of the clinical and field trials. 
falciparum
in a mouse liverImage courtesy of Seattle
Biomedical Research Institute
A new compound can fight multidrug-resistant malaria, according to preclinical research published in Science Translational Medicine.
The compound, DSM265, targets DHODH, an enzyme involved in the malaria parasite’s production of nucleotides.
Experiments showed that DSM265 can target the parasite at both the blood and liver stages of infection. And the compound appeared to be safe.
Based on these results, DSM265 has advanced to clinical trials.
Investigators believe the drug could potentially be partnered with other antimalarials for a single-dose treatment or once-weekly prophylaxis.
“This is the first of a new class of molecules that’s going into humans,” said study author Pradipsinh Rathod, PhD, of the University of Washington in Seattle.
“Until now, everything else in humans has been variations of drugs that have been developed in the distant past.”
The investigators tested DSM265 in multiple models, including human cells, rodents, dogs, and monkeys.
DSM265 arrested growth of the Plasmodium falciparum parasite at both the blood and liver stages. And the drug was active against P falciparum strains that were resistant to chloroquine and pyrimethamine.
DSM265 also proved to be long-acting. Experiments suggested a dose of 200 mg to 400 mg would maintain therapeutic concentrations in humans for at least 8 days.
Repeated doses of DSM265, given to mice and dogs, did not cause major side effects. The researchers said DSM265 was well tolerated at all dose levels given to mice (25 to 200 mg/kg per day once daily for 7 days) and dogs (30 to 480 mg/kg every other day for 10 days).
None of the animals died, and there were no clinical effects observed in the mice. Dogs receiving the highest dose of DSM265 experienced vomiting, apparent loss of appetite, and a slight increase in bilirubin that was not accompanied by changes in any other liver function markers.
Dr Rathod said he hopes the development and discovery pipeline for DSM265 will pave the way for a faster and more collaborative drug development process in “the long war against malaria.”
In an attempt to accelerate the drug’s development, the investigators transferred their patent rights for DSM265 to the Medicines for Malaria Venture, a Bill & Melinda Gates Foundation-supported nonprofit that is leading some of the clinical and field trials.
falciparum
in a mouse liverImage courtesy of Seattle
Biomedical Research Institute
A new compound can fight multidrug-resistant malaria, according to preclinical research published in Science Translational Medicine.
The compound, DSM265, targets DHODH, an enzyme involved in the malaria parasite’s production of nucleotides.
Experiments showed that DSM265 can target the parasite at both the blood and liver stages of infection. And the compound appeared to be safe.
Based on these results, DSM265 has advanced to clinical trials.
Investigators believe the drug could potentially be partnered with other antimalarials for a single-dose treatment or once-weekly prophylaxis.
“This is the first of a new class of molecules that’s going into humans,” said study author Pradipsinh Rathod, PhD, of the University of Washington in Seattle.
“Until now, everything else in humans has been variations of drugs that have been developed in the distant past.”
The investigators tested DSM265 in multiple models, including human cells, rodents, dogs, and monkeys.
DSM265 arrested growth of the Plasmodium falciparum parasite at both the blood and liver stages. And the drug was active against P falciparum strains that were resistant to chloroquine and pyrimethamine.
DSM265 also proved to be long-acting. Experiments suggested a dose of 200 mg to 400 mg would maintain therapeutic concentrations in humans for at least 8 days.
Repeated doses of DSM265, given to mice and dogs, did not cause major side effects. The researchers said DSM265 was well tolerated at all dose levels given to mice (25 to 200 mg/kg per day once daily for 7 days) and dogs (30 to 480 mg/kg every other day for 10 days).
None of the animals died, and there were no clinical effects observed in the mice. Dogs receiving the highest dose of DSM265 experienced vomiting, apparent loss of appetite, and a slight increase in bilirubin that was not accompanied by changes in any other liver function markers.
Dr Rathod said he hopes the development and discovery pipeline for DSM265 will pave the way for a faster and more collaborative drug development process in “the long war against malaria.”
In an attempt to accelerate the drug’s development, the investigators transferred their patent rights for DSM265 to the Medicines for Malaria Venture, a Bill & Melinda Gates Foundation-supported nonprofit that is leading some of the clinical and field trials.