Promising results for a new anti-malaria drug

Malaria It is one of the deadliest diseases in human history. Its cause is not a bacterium or a virus, but a single-celled parasite called Plasmodium (Plasmodium), which is transmitted to humans by the bite of the Anopheles mosquito. After infection, the parasite migrates to the liver, multiplies, then invades our red blood cells and explodes them. The result is fever attacks, chills, anemia and in many cases death.

dictation Originally published on the Davidson Institute for Science Education website

For over 25 years, the world’s main line of defense against malaria has consisted of one drug – artemisinin, or its daughter drugs, always in combination with other drugs. The reason for this is that when treating infectious diseases, the use of only one drug may lead to the development of resistant pathogens, against which the drug is ineffective.

This dangerous process occurs because when a cell divides into two, random errors (mutations) can occur in its genetic material. Here and there, such an error may give the creature causing the disease a new feature that allows it to survive in the presence of the drug. Then, when the medicine is given to the patient, almost all the causative agents of the disease will be destroyed, but not the resistant individuals. This way the trait that gives resistance to the drug will spread, as only the survivors will be able to spread their traits to future generations. That is why it is very important to always attack the parasite on two fronts at the same time, since it is very unlikely that the pathogen will simultaneously develop two separate mutations that will give it resistance against two different drugs that work by other mechanisms.

Artemisinin itself works in a way that resembles a bomb: it enters the blood cells and creates an explosion of free radicals that kill the parasite residing inside the cell. Combined treatment, therefore, must include an additional drug that will attack the plasmodium in a different way. But since medical treatments are not always done “by the book”, mistakes are sometimes made, and some may allow resistant strains to develop. Indeed, in recent years, alarming reports have been received from Southeast Asia and Equatorial Africa, where malaria is particularly common, about parasite strains that have developed partial resistance to artemisinin. Their durability prolongs the recovery time and affects the effectiveness of the treatment.

The solution could come in the form of a new drug, which would provide an effective alternative treatment to artemisinin. recently reported The pharmaceutical company Novartis for significant progress in development a new drug Named GanLum, after the two active substances contained in it: ganaplacide (ganaplacide) and lumefantrine (lumefantrine). The drug successfully faced malaria in a large trial, and it represents the first in about 25 years of a new drug family developed against the disease that is not based on artemisinin. The treatment is given by swallowing (tablets), usually once a day for three days only. This is a very simple treatment method, which will facilitate the use of the drug in remote and poor areas where malaria is particularly common.

GanLum’s main innovation is its first component: Gnaplacid, A substance that belongs to a new chemical family and works in a unique mechanism. Studies show that compounds from this family disrupt the parasite’s protein secretion and transport pathways, meaning the system responsible for the production, sorting and transfer of proteins to organelles and other targets within the cell. The parasite depends on this transport system to function inside the patient’s red blood cells. When this system is blocked, the parasite stops multiplying, withers and dies.

Of course, Gnaplacid may also develop resistance: a study found that mutations do occur In a garden related to the transportation system of the parasite reduce its sensitivity to compounds from the family, but this is only a partial resistance, which does not completely eliminate the effect of the drug. Despite this drawback, the mechanism of action of gnaplacid is very important, as it is completely different from that of artemisinin and its derivatives. Therefore, he offers a treatment that can also help those who have been infected with strains of Plasmodium that have developed resistance to artemisinin.

Lumifantrine, the second component in GanLum is an old and well-known drug that has been used until now as an addition to artemisinin. Its combination with gnaplacid should be effective because their mechanism of action is different: lumifantrine probably poisons the parasite by not allowing it to break down a blood component called heme, which is toxic to it. Also, the timing of the activity of the two components is different: Ganaplacid acts quickly and eliminates most of the parasites, while lumifantrine stays in the blood longer, thus eliminating the stubborn parasites that still remain.

The new drug is not yet approved for use, but according to the company’s reports, the findings of its clinical trials are very encouraging. in a large clinical trialwhich took place in 12 countries in Africa, with the participation of approximately 1,700 adults and children, it showed cure rates similar to and even slightly higher than the standard treatment with artemisinin. In some measures, its effectiveness reached 97.4 percent, compared to 94 percent in the existing treatment. In patients with Plasmodium strains that developed initial resistance to artemisinin, GanLum cleared the parasite from the blood in an average of 47 hours, compared to 71 hours with the existing treatment.

Another advantage of GanLum is its potential to interrupt the chain of infection with the parasite. The drug can also damage the parasite during the sexual reproduction stage, where it does not yet cause the disease but can pass from the infected person to the mosquito that will bite him, and through it spread the disease further. By eliminating the parasite at this stage of life, the drug not only cures the patient, but also helps stop the spread of the epidemic in the community.

Currently, Novartis, which is developing the drug with the assistance of the Medicines for Malaria Venture organization, Progressing in the registration and approval processes of the new treatment. If all goes well, within a year to a year and a half we will see GanLum join the anti-malaria medicine cabinet. The existence of an alternative with a new mechanism of action will allow doctors to switch between drugs, make it difficult for the parasite to develop resistance and stay one step ahead of the deadly parasite in the race to save lives.