Advances in biology and medical chemistry, coupled with increased investment in research, have led to some of the major neglected tropical diseases accumulating promising candidates for new treatments in recent years. However, worms, which among these diseases affect more people in the world in absolute numbers, have made little progress in terms of transmitting research in vitro For preclinical and clinical trials.
This is one of the conclusions of a study published in Drug Discovery Today magazine by researchers from the University of Sao Paulo (USP) and the University of Guarulhus.
“More than a billion people worldwide are affected by worms, but these are the least treated diseases, even among the so-called neglected diseases. Schistosomiasis alone has 250 million people infected and there is only one cure, while the others get more resources to seek treatment options,” says Joshua. De Moras, a researcher supported by FAPESP who coordinates the Nuclear Disease Research Foundation (NPDN) at the Universidade Guarulhos, one of the authors of the article.
In 2021, the World Health Organization (WHO) launched an action plan to eradicate or control, by 2030, 20 diseases that affect one in five people in the world and kill about 500,000 a year, the vast majority of them poor.
Among the goals is the development of new drugs, as these diseases are characterized by a lack of effective treatments and vaccines.
In the study, the researchers report that despite the historical lack of innovation in drugs for these diseases, public-private, non-profit partnerships have funded and accelerated the discovery of potential new drugs, using modern medical chemistry strategies.
“Drug development strategies have undergone profound changes in recent years. In the past a random survey was conducted, testing compounds for infectious agents trial and error. With the advancement of medical chemistry and experimental and computational tools, this can now be done. More rational screening before testing on the bench,” explains another The research, Adriano Andricopolo, is a professor at the Sao Carlos Institute of Physics (IFSC-USP) and a researcher at the Center for Innovation in Biodiversity and Medicine (CIBFar).
CIBFar is one of the research, innovation and distribution (CEPIDs) supported by FAPESP.
Silent diseases
The researchers note that great strides have been made in potential new treatments for leishmaniasis, Chags’ disease and African human trypanosomiasis (HAT), also known as sleeping sickness. However, the same does not happen with vermin such as schistosomiasis.
Currently, a number of compounds are in clinical trials for leishmaniasis. In contrast, studies on Chugs’ disease face difficulties in advancing from the discovery of potential drugs to the preclinical phase.
The complex biology of the parasite causing the disease, e Crucial trypanosome And its interaction with various human tissues remains major challenges for scientists.
“Most parasitic diseases are chronic, silent. In the case of Chagas, when the person receives the diagnosis it is because he usually already has heart failure, when the parasite is installed in the heart tissue. The challenge is to get the drug to reach T. cruzi without harming the patient,” Explains Moras.
The authors add, however, that recent studies have revealed new molecular targets and signaling pathways in the parasite that may contribute to the discovery of new therapies.
In the case of HAT, caused by Trypanosoma brucei Approval in 2021 for the use of the drug fexinidazole represents a major step forward, as it is the first oral treatment for the disease.
On the other hand, diseases caused by worms, such as those of the genus Schistosome Still a step behind and they don’t even have compounds in advanced detection stages.
Repositioning of the drug is considered promising for worms, as in the case of Miltphosin, which has been known since the 1980s to treat cancer and is currently used against leishmaniasis.
Recently, the group led by Moras described how an anti-inflammatory drug reduced the parasite load in mice infected with mice by more than 80% schistosoma mansoni.
In addition, research on basic aspects of worm biology has progressed and revealed new molecular targets. There are still promising studies with a compound that works against both adult and small parasites.
Despite this, the authors consider these efforts insufficient, given the high prevalence of vermin in the world. Therefore, multidisciplinary and collaborative drug discovery programs for these diseases should be strengthened.
“One of the difficulties in studying worms is to cultivate the parasites in the laboratory. While trypanosomes and plasmodia [como o causador da malária] Can be maintained more easily, for the worms need rodents and snails, which represent the final and medium hosts. As a result, studies go much further for other parasites, “says Moras.
Due to such difficulties, the researcher emphasizes that the eradication of these diseases requires, in addition to drug development, additional measures for public health, such as diagnosis, control of transfer vectors and universal basic sanitation. “The means must be multiple, these diseases cannot be terminated only with the use of drugs,” he says.