Fiocruz presents studies on neglected diseases and COVID-19 at Pasteur Network meeting

Fiocruz researchers presented work involving neglected diseases such as leprosy and malaria, as well as COVID-19, at the Annual Meeting of the Pasteur Network, which began 10/21 in Rio de Janeiro and is being held for the first time in the Americas, co-organized by the Foundation. Among the topics of the studies presented are the selection and formulation of more effective treatments and vaccines that do not yet exist in the country. These three are among the 14 studies selected from scientists from more than 30 institutions in 25 countries that make up the Pasteur Network. They were developed by researchers from the Oswaldo Cruz Institute (IOC/Fiocruz), Fiocruz Rondônia and Fiocruz Pernambuco, in partnership with other members of the network.

Leprosy The work of the IOC/Fiocruz's Cellular Microbiology Laboratory on leprosy, published in 2023, should be highlighted at the meeting. Faced with the lack of specific treatment for the neuropathy caused by leprosy, the researchers developed a platform for testing neuroprotective drugs capable of managing this issue. The model then allows for the screening and possible repositioning of drugs that can inhibit the metabolic remodeling of the Schwann cell.

In partnership with the Lauro de Souza Lima Institute, the researchers have developed a model of leprosy neuropathy in mice, which will be used to validate drugs and deepen our understanding of the molecular mechanisms responsible for the onset of neural damage in leprosy. The work also involved a partnership with the Pasteur Institute. The study is currently at the in vitro stage and the next step is the in vivo stage expected next year. By 2030, clinical trials are expected to begin on fatty acid synthesis inhibitors, which are currently used to treat diabetes and cancer.

Coordinator of the study, researcher Flavio Lara explains that leprosy is a socially determined disease with little investment from pharmaceutical companies - the last treatment was launched around 30 years ago. One of the big issues today is that the neuropathy associated with the disease has no specific treatment. The IOC/Fiocruz study seeks to understand the molecular basis of neuropathy to find drugs capable of curbing it.

"We are demonstrating that one of the problems of neuropathy is that bacterial antigens are able to persist in the tissues and continue to promote the remodeling of Schwann cell metabolism, leading to the loss of physical and metabolic support for the axon. We are managing to find the key points of this signaling and inhibit them with drugs already available on the market," says Lara. "Thus, as soon as we receive the diagnosis, it will be possible to introduce some of these accessory drugs to protect the patients' nerves."

COVID-19

Considered a pioneer in the country, another study to be presented at the meeting is a Fiocruz Pernambuco project coordinated by researcher Fabio Formiga on the formulation of monoclonal antibodies (mAbs) using nanotechnology for the treatment of COVID-19. Currently, the option recommended by the World Health Organization for moderate and severe cases of the disease is intravenous use, which limits the reach of the antibody in the lungs.

The project developed nanoparticles capable of incorporating the antibody and targeting it to lung tissue with greater potential for selectivity and efficacy. With gradual and controlled release, the main advantage of the nanoformulation is that it promotes local action of the mAb in the lung tissue, mitigating the inflammatory response caused by the COVID-19 infection. A patent feasibility study is also underway.

For Formiga, the project has shown promising results: "The nanoformulation demonstrated efficient association with the antibody, stability, compatibility with lung cells and lung deposition in tests with mice. Our research opens up prospects for new stages in the development of the formulation in the form of an aerosol for inhalation use," says the researcher. "The technology could even be adapted for other lung infections in the future - which further strengthens the potential of this project."

The project was designed in partnership with the Pasteur Institute in Montevideo, where pre-clinical tests were carried out on the safety and pulmonary deposition of the nanoformulation in mice. The Physics Institute of the University of São Paulo (USP) and the Niels Bohr Institute of the University of Copenhagen (Denmark) also took part in the project.

Malaria

The project developed by Fiocruz Rondônia, coordinated by researcher Maisa Araújo, aims to generate monoclonal antibodies against the infective phase of Plasmodium vivax, a species of malaria that is endemic in the Brazilian Amazon region, for the future generation of a transmission-blocking vaccine, which does not yet exist in Brazil. The scientists are currently at the stage of selecting specific peptides with a view to selecting antibodies produced naturally by individuals from endemic areas who have had more than three vivax malaria infections.

Malaria is the deadliest vector-borne disease in the world; infection begins when sporozoites are inoculated into the host's skin after a mosquito bite. In Brazil, most cases of the disease are caused by Plasmodium vivax, which can remain dormant for weeks to months. It can also be clinically silent. Recent advances have shown that passive immunization with a dose of human monoclonal antibody (hmAb) against a specific protein (circumsporozoite, CSP, of Plasmodium falciparum, the main surface protein of sporozoites) can completely block infection by Pf sporozoites.

Based on this, the project proposal aims to generate potent recombinant hmAbs that target Pv sporozoites, thus controlling the primary infection and subsequent relapses.

Starting in June, the team received approval from the ethics committee in October to recruit participants for the study. In partnership with the Pasteur Institute, the work was approved through a Fiocruz - Pasteur Institute - USP Call 2023. From Fiocruz Rondônia, in addition to Maisa Araújo, researcher Jansen Medeiros is taking part in the study.