Advances in biology and medicinal chemistry, together with increased investment in research, have made some important neglected tropical diseases promising candidates for new treatments in recent years. However, worms, which affect the most people in the world in absolute terms, have not been well studied. Inside the slaughterhouse For preclinical and clinical trials
This is one of the results of a study published in the journal Drug Discovery Today by researchers from the University of São Paulo (USP) and the University of Guarulhos.
He added: More than one billion people in the world are infected with worms, but these diseases have the lowest prevalence, even among the so-called neglected diseases. “Look for treatment options.” Josué de Moraes, a researcher supported by FAPESP and coordinator of the Research Core in Neglected Diseases (NPDN) at the University of Guarulhos, co-author of the paper.
In 2021, the World Health Organization (WHO) plans to eradicate or control by 2030 20 diseases that affect one in five people in the world and kill about 500,000 people annually, the vast majority of whom are poor. performed
Among the goals is the development of new drugs, because these diseases are characterized by the lack of effective treatments and vaccines.
In this study, the researchers report that despite a historical lack of drug innovation for these diseases, partnerships between public, private and nonprofit initiatives have funded and accelerated the discovery of potential new drugs using modern medicinal chemistry strategies.
Drug production strategies have undergone profound changes in recent years, in the past, random screening was done and compounds were tested on infectious agents by trial and error, and with the advancement of medicinal chemistry and experimental and computational tools, today it is possible to perform a rational screening. Another study author, Adriano Andrecopoulo, professor at the São Carlos Institute of Physics (IFSC-USP) and researcher at the Center for Innovation in Biodiversity and Medicine (CIBFar) explains, before performing bench tests.
CIBFar is one of the Centers for Research, Innovation and Dissemination (CEPID) supported by FAPESP.
Silent diseases
Major advances have been made in potential new treatments for leishmaniasis, Chagas disease and human African trypanosomiasis (HAT), also known as sleeping sickness, the researchers note. However, this is not the case with invasive parasites such as schistosomiasis.
Several compounds are currently in clinical trials for leishmaniasis. In contrast, studies on Chagas disease face difficulties in progressing from the discovery of potential drugs to the preclinical stage.
The complex biology of the disease-causing parasite, Trypanosoma cruzi And its interaction with different human tissues is the main challenge of scientists.
“Most parasitic diseases are chronic and silent. In the case of Chagas, the time a person is diagnosed is because they usually already have heart failure and the parasite has established itself in the heart tissue. The challenge is to make medicine available. Moraes explains that T. cruzi without harming the patient.
However, the authors add that recent studies have revealed new molecular targets and signaling pathways in the parasite that may help discover new treatments.
In the case of HAT, caused by Trypanosoma brusi the 2021 approval for the drug fexinidazole represents a major advance, as it is the first oral treatment for the disease.
On the other hand, diseases caused by worms, such as those worms Schistosoma are still a step behind and do not even have compounds in the advanced stages of discovery.
Drug transfer is considered promising for worms, as in the case of miltefosine, which has been known to treat cancer since the 1980s and is currently used to treat leishmaniasis.
Recently, a group led by Moraes described how an anti-inflammatory drug reduced the parasite load by more than 80% in parasite-infected mice. Schistosoma mansoni.
In addition, research on fundamental aspects of the worm’s biology has advanced and revealed new molecular targets. There are still promising studies on a combination that works against both adult and juvenile parasites.
However, the authors consider these efforts to be insufficient due to the high prevalence of pests in the world. Therefore, multidisciplinary and collaborative drug discovery programs for these diseases should be strengthened.
“One of the difficulties in studying worms is the cultivation of parasites in the laboratory. While trypanosomes and plasmodia [como o causador da malária] can be kept more easily, for worms it is necessary to have rodents and snails that represent definitive and intermediate hosts. As a result, studies for other parasites go much further.”
Considering such problems, the researcher emphasizes that the eradication of these diseases, in addition to drug development, requires other public health measures such as diagnosis, control of transmission vectors, and general public health. He says: The measures must be multiple, these diseases cannot be ended by using medicine alone.