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
- Akufo-Addo received malaria vaccine, not coronavirus jab – Hassan Ayariga allegeson June 12, 2021 at 8:40 am
President Nana Addo Dankwa Akufo-Addo has yet to receive the real COVID-19 vaccine • According to Hassan Ayariga, Akufo-Addo received a malaria vaccine • Ghana started vac ...
- Covid jab tech helps fight malariaon June 12, 2021 at 6:11 am
A malaria vaccine with 77% efficacy in children from birth to five years old — the age group with the highest fatality rate worldwide — is in the early stages of human trials at Oxford University. The ...
- Fresh Hope for Malaria Vaccine from Newly Discovered Parasitic Antigenson June 11, 2021 at 5:00 am
Scientists have discovered two new antigens in a species of malaria-causing parasite P. falciparum that elicit antibodies that appear in humans and are linked with lower malaria transmission in mice.
- Unaffordable treatment for severe malaria highlights U.S. drug market pitfallson June 11, 2021 at 1:40 am
In the U.S., the drug to treat severe malaria used to cost $200. The new one costs $30,000. Clarity is needed on drugs for rare diseases.
- Study offers new insight into one of the mysteries of natural immunity to malariaon June 10, 2021 at 8:00 am
In the first and largest global metabolomic study of African children before and after malaria infection, NYU Abu Dhabi Assistant Professor of Biology Youssef Idaghdour and his colleagues at the ...
- New Insight Into One of the Mysteries of Natural Immunity to Malariaon June 10, 2021 at 8:00 am
Researchers compared metabolic responses to human malaria in children of different populations. In 2019, 409,000 people died of malaria--most were young children in sub-Saharan Africa. The annual ...
- Malaria Diagnostics Market to Record 5.10% CAGR Through 2030on June 10, 2021 at 6:48 am
The Malaria Diagnostics market is estimated to reach USD 661.30 Mn in 2021, at a CAGR of 5.10% during the forecast period. Hence, the need for different types of diagnostic tests plays a vital role in ...
- NYUAD study offers new insight into one of the mysteries of natural immunity to malariaon June 9, 2021 at 9:00 pm
The team studied blood samples from children from two ethnic groups in remote rural areas of Burkina Faso, Gouin and Fulani, to see how they responded to the malaria parasite Plasmodium falciparum.
- She Dances With The Stars, But How Is Choreographer Sherrie Silver Helping End Malaria?on June 8, 2021 at 10:27 am
Sherrie Silver is calling on young Africans and people around the world to take a stand against malaria once and for all.
- Malaria is far deadlier in Africa than the coronavirus. Why is the vaccine taking so long?on June 7, 2021 at 3:52 am
We are all frustrated in Africa to see how covid gets so much attention compared to malaria,” said epidemiologist Halidou Tinto, regional director of Burkina Faso’s Institute of Research in Health ...
via Bing News