Nitisinone, a drug for uncommon ailments, kills mosquitoes when current in human blood and should develop into a brand new device to struggle malaria, providing longer-lasting, environmentally safer results than ivermectin.
Controlling mosquito populations is a key technique within the struggle towards malaria.
Presently, a number of approaches are used to cut back mosquito numbers and restrict malaria transmission. One technique includes the usage of the antiparasitic drug ivermectin. When mosquitoes feed on blood containing ivermectin, their lifespan is shortened, which might cut back the unfold of the malaria parasite.
Nonetheless, ivermectin presents challenges. It’s poisonous to the setting, and its widespread use in each people and animals to deal with parasitic infections raises the danger of drug resistance.
Now, a examine printed in Science Translational Drugs has recognized a promising different. Researchers found that when folks take the remedy nitisinone, their blood turns into deadly to mosquitoes, providing a possible new device for mosquito management and malaria prevention.
How Nitisinone Works
“One strategy to cease the unfold of ailments transmitted by bugs is to make the blood of animals and people poisonous to those blood-feeding bugs,” stated Lee R. Haines, affiliate analysis professor of organic sciences on the College of Notre Dame, honorary fellow on the Liverpool Faculty of Tropical Drugs and co-lead creator of the examine. “Our findings counsel that utilizing nitisinone may very well be a promising new complementary device for controlling insect-borne ailments like malaria.”
Usually, nitisinone is a medicine for people with uncommon inherited ailments — resembling alkaptonuria and tyrosinemia sort 1 — whose our bodies wrestle to metabolize the amino acid tyrosine. The remedy works by blocking the enzyme 4-hydroxyphenylpyruvate dioxygenase (HPPD), stopping the build-up of dangerous illness byproducts within the human physique. When mosquitoes drink blood that comprises nitisinone, the drug additionally blocks this significant HPPD enzyme of their our bodies. This prevents the mosquitoes from correctly digesting the blood, inflicting them to shortly die.
The researchers analyzed the nitisinone dosing concentrations wanted for killing mosquitoes, and the way these outcomes would stack up towards ivermectin, the gold customary ectoparasitic drug (remedy that particularly targets ectoparasites resembling mosquitoes).
“We thought that if we wished to go down this route, nitisinone needed to carry out higher than ivermectin,” stated Álvaro Acosta Serrano, professor of organic sciences at Notre Dame and co-corresponding creator of the examine. “Certainly, nitisinone efficiency was incredible; it has a for much longer half-life in human blood than ivermectin, which suggests its mosquitocidal exercise stays circulating within the human physique for for much longer. That is crucial when utilized within the subject for security and economical causes.”
Testing Nitisinone in People
The analysis staff examined the mosquitocidal impact of nitisinone on feminine Anopheles gambiae mosquitoes, the first mosquito species liable for spreading malaria in lots of African nations. If these mosquitoes develop into contaminated with malaria parasites, they unfold the illness after they feast on a human.
To guage how the drug affected the mosquitoes when fed recent human blood containing nitisinone, researchers collaborated with the Robert Gregory Nationwide Alkaptonuria Centre on the Royal Liverpool College Hospital. The middle was performing nitisinone trials with folks recognized with alkaptonuria, who then donated their blood for the examine. These taking nitisinone have been discovered to have blood that was lethal to mosquitoes, which Haines describes as having a “hidden superpower.”
The analysis staff collected knowledge on how the drug was metabolized in peoples’ blood, permitting the staff to fine-tune their modeling and supply pharmacological validation of nitisinone as a possible mosquito inhabitants management technique.
Nitisinone was proven to last more than ivermectin within the human bloodstream, and was capable of kill not solely mosquitoes of all ages — together with the older ones which can be almost certainly to transmit malaria — but in addition the hardy mosquitoes immune to conventional pesticides.
“Sooner or later, it may very well be advantageous to alternate each nitisinone and ivermectin for mosquito management,” Haines stated. “For instance, nitisinone may very well be employed in areas the place ivermectin resistance persists or the place ivermectin is already closely used for livestock and people.”
Subsequent Steps and Broader Impacts
Subsequent, the analysis staff goals to discover a semi-field trial to find out what nitisinone dosages are greatest linked to mosquitocidal efficacy within the subject.
“Nitisinone is a flexible compound that may also be used as an insecticide. What’s significantly attention-grabbing is that it particularly targets blood-sucking bugs, making it an environmentally pleasant possibility,” Acosta Serrano stated.
As an unintended profit, extending the usage of nitisinone as a vector management device may consequently enhance drug manufacturing and reduce the worth of the remedy for sufferers affected by uncommon genetic ailments within the tyrosine metabolism pathway.
Reference: “Anopheles mosquito survival and pharmacokinetic modeling present the mosquitocidal exercise of nitisinone” by Lee R. Haines, Anna Trett, Clair Rose, Natalia García, Marcos Sterkel, Dagmara McGuinness, Clément Regnault, Michael P. Barrett, Didier Leroy, Jeremy N. Burrows, Giancarlo Biagini, Lakshminarayan R. Ranganath, Ghaith Aljayyoussi and Álvaro Acosta-Serrano, 26 March 2025, Science Translational Drugs.
DOI: 10.1126/scitranslmed.adr4827
The examine was funded by the UK Medical Analysis Council, Biotechnology and Organic Sciences Analysis Council, Wellcome Belief Institutional Strategic Assist Fund, the Medical Analysis Council Doctoral Coaching Partnership and the College of Glasgow Wellcome Centre for Integrative Parasitology.
