An international research collaborative has determined that a promising anti-malarial compound tricks the immune system to rapidly destroy red blood cells infected with the malaria parasite but leave healthy cells unharmed.
St. Jude Children’s Research Hospital scientists led the study, which appears in the current online early edition of the Proceedings of the National Academy of Sciences (PNAS).
The compound, (+)-SJ733, was developed from a molecule identified in a previous St. Jude-led study that helped to jumpstart worldwide anti-malarial drug development efforts. Malaria is caused by a parasite spread through the bite of an infected mosquito. The disease remains a major health threat to more than half the world’s population, particularly children. The World Health Organization estimates that in Africa a child dies of malaria every minute.
In this study, researchers determined that (+)-SJ733 uses a novel mechanism to kill the parasite by recruiting the immune system to eliminate malaria-infected red blood cells. In a mouse model of malaria, a single dose of (+)-SJ733 killed 80 percent of malaria parasites within 24 hours. After 48 hours the parasite was undetectable.
Planning has begun for safety trials of the compound in healthy adults.
Laboratory evidence suggests that the compound’s speed and mode of action work together to slow and suppress development of drug-resistant parasites. Drug resistance has long undermined efforts to treat and block malaria transmission.
“Our goal is to develop an affordable, fast-acting combination therapy that cures malaria with a single dose,” said corresponding author R. Kiplin Guy, Ph.D., chair of the St. Jude Department of Chemical Biology and Therapeutics. “These results indicate that SJ733 and other compounds that act in a similar fashion are highly attractive additions to the global malaria eradication campaign, which would mean so much for the world’s children, who are central to the mission of St. Jude.”
Whole genome sequencing of the Plasmodium falciparum, the deadliest of the malaria parasites, revealed that (+)-SJ733 disrupted activity of the ATP4 protein in the parasites. The protein functions as a pump that the parasites depend on to maintain the proper sodium balance by removing excess sodium.
The sequencing effort was led by co-author Joseph DeRisi, Ph.D., a Howard Hughes Medical Institute investigator and chair of the University of California, San Francisco Department of Biochemistry and Biophysics. Investigators used the laboratory technique to determine the makeup of the DNA molecule in different strains of the malaria parasite.
Researchers showed that inhibiting ATP4 triggered a series of changes in malaria-infected red blood cells that marked them for destruction by the immune system. The infected cells changed shape and shrank in size. They also became more rigid and exhibited other alterations typical of aging red blood cells. The immune system responded using the same mechanism the body relies on to rid itself of aging red blood cells.
Another promising class of antimalarial compounds triggered the same changes in red blood cells infected with the malaria parasite, researchers reported. The drugs, called spiroindolones, also target the ATP4 protein. The drugs include NITD246, which is already in clinical trials for treatment of malaria. Those trials involve investigators at other institutions.
“The data suggest that compounds targeting ATP4 induce physical changes in the infected red blood cells that allow the immune system or erythrocyte quality control mechanisms to recognize and rapidly eliminate infected cells,” DeRisi said. “This rapid clearance response depends on the presence of both the parasite and the investigational drug. That is important because it leaves uninfected red blood cells, also known as erythrocytes, unharmed.”
Laboratory evidence also suggests that the mechanism will slow and suppress development of drug-resistant strains of the parasite, researchers said.
The Latest on: Malaria
via Google News
The Latest on: Malaria
- ‘Delayed diagnosis of malaria, dengue as Covid-19 co-infection may lead to miscarriage’on October 11, 2020 at 11:48 am
Late diagnosis of Covid-19 infection with dengue and malaria in pregnant women can lead to health complications including miscarriage, revealed a study conducted by the Indian Council of Medical ...
- ‘More affordable anti-malaria drugs needed’on October 10, 2020 at 5:00 pm
A pharmaceutical manufacturer, May & Baker Nigeria Plc, has underscored the need for more inexpensive medicines for the treatment of malaria. The Managing Director, May & Baker, Mr Nnamdi Okafor, at a ...
- Chloroquine Market | Increasing Prevalence of Malaria to Boost the Market Growth | Technavioon October 9, 2020 at 7:41 pm
The global chloroquine market size is poised to grow by USD 86.12 million during 2020-2024, progressing at a CAGR of almost 3% throughout the forecast period, according to the latest report by ...
- Findings could bring hope for novel therapeutic strategies against malariaon October 9, 2020 at 6:56 am
The Plasmodium parasite, which transmits malaria to humans through infected mosquitos, triggers changes in human genes that alter the body's adaptive immune response to malarial infections, according ...
- Researchers discover immune evasion strategy used by Malaria-causing parasiteon October 9, 2020 at 6:07 am
The plasmodium parasite, which transmits malaria to humans through infected mosquitos, triggers changes in human genes that alter the body's adaptive immune response to malarial infections ...
- NYUAD researchers discover immune evasion strategy used by Malaria-causing parasiteon October 9, 2020 at 2:08 am
A team of researchers at NYU Abu Dhabi (NYUAD) has found that the Plasmodium parasite, which transmits malaria to humans through infected mosquitos, triggers changes in human genes that alter the body ...
- Life-saving malaria campaigns on track in the majority of malaria-affected countries despite COVID-19on October 8, 2020 at 5:00 pm
New data confirms that over 90% of life-saving malaria intervention campaigns scheduled for this year are on track across Africa, Asia and the Americas, helping to protect millions from the disease ...
- New model may explain rarity of certain malaria-blocking mutationson October 8, 2020 at 11:02 am
A new computational model suggests that certain mutations that block infection by the most dangerous species of malaria have not become widespread in people because of the parasite's effects on the ...
- Atomwise Receives a $2.3M Grant to Develop New Therapies for Drug Resistant Malaria and Tuberculosison October 6, 2020 at 6:14 am
The $2.3M in grant funding from the Bill & Melinda Gates Foundation will support the development of multiple global health programs to advance novel antimalarial and anti-tuberculosis small molecule ...
- Understanding how the malaria parasite can withstand fever's heaton October 5, 2020 at 3:30 pm
Even when a person suffering from malaria is burning up with fever and too sick to function, the tiny blood-eating parasites lurking inside them continue to flourish, relentlessly growing and ...
via Bing News