Researchers from Brazil and Italy search industrial waste for new Alzheimer’s drugs

One of the raw materials studied by the group is cashew nut shell liquid, a by-product of oilseed processing; work was presented during FAPESP Week Italy.

By Karina Toledo, from Bologna  |  Agência FAPESP – A self-proclaimed Brazil-Italy collaboration enthusiast, researcher Laura Bolognesi created the B2AlzD2 Joint Lab at the Department of Pharmacy and Biotechnology of the Università di Bologna (UNIBO), the first Brazil-Bologna joint laboratory dedicated to the development of new drugs for the treatment of Alzheimer’s disease. The partners include scientists from four Brazilian universities: the Federal University of Rio de Janeiro (UFRJ), the University of Brasília (UnB), the University of São Paulo (USP Ribeirão Preto) and the Federal University of Minas Gerais (UFMG).

One of the laboratory’s ongoing projects is to identify compounds with the potential for drug development in industrial waste, particularly in cashew nut shell liquid (CNL), a natural oil considered to be a by-product of the industrial processing of cashew nuts, with a high content of phenolic compounds.

The line of research and the principles that guide the group’s work were presented by Bolognesi on Tuesday (Oct 15th) in a panel discussion on health and the environment that was part of the program of FAPESP Week Italy.

“We need to integrate the concept of sustainability into the search for bioactive molecules. This must be the keyword,” said Bolognesi in her presentation. “If we adopt waste as a raw material for drug development, the products resulting from the research will be inherently sustainable.”

The group’s work also takes a One Health approach, Bolognesi said. Conceived at the turn of the century, this concept refers to an integrated approach that recognizes the link between human, animal, plant and environmental health. “It’s a holistic vision in which everyone involved must be included. We believe that it’s not enough just to find a new drug that’s potent and bioavailable. It must also be accessible to the people who need it. In the case of Chagas disease, for example, more than 90% of affected patients don’t have access to treatment, even though they live in three major economies [Brazil, Argentina and Mexico],” she noted.

Another concern of the B2AlzD2 Joint Lab, said Bolognesi, is to integrate green chemistry principles into its drug development pipeline.

Neglected diseases

Luiz Carlos Dias, a professor at the State University of Campinas (UNICAMP), was another member of the panel. He presented the work of an international consortium created to support the search for new drugs against Chagas disease and malaria. The initiative brings together UNICAMP, USP and two non-profit organizations: the Drugs for Neglected Diseases Initiative (DNDi) and the Medicines for Malaria Venture (MMV). The group is supported by FAPESP through the Research Partnership for Technological Innovation Program (PITE) (read more at: agencia.fapesp.br/32265).

“Our work touches on several SDGs [Sustainable Development Goals of the 2030 Agenda], and its central goal is to reduce the time it takes to discover drugs,” he said.

Dias explained to Agência FAPESP that the consortium receives information from the DNDi and the MMV about the structure of the molecules to be studied, all of which are off-patent. “We synthesize the substances at UNICAMP, purify them and send them to various Brazilian laboratories in the network to be tested against the parasite. For those that show anti-parasitic activity, we develop analogous molecules with minor modifications to try to increase potency, stability and safety. Only after many in vitro tests have we moved on to animal testing. Our challenge now is to develop a viable compound for a clinical trial.”

At the beginning of the project, he said, this entire pre-clinical testing phase was done outside Brazil because there was no installed capacity in the country. “Today, we do the whole cascade of tests, the primary and secondary parasitology part. We’ve acquired a competence that we didn’t have because the country never invested in drug discovery and development. We’ve built a network with various partners with experience in different areas,” he commented.

Dias reflects that the group’s challenges are great and the goals are ambitious: to develop low-cost drugs that are safe enough to be used by children and pregnant women, who are among the main populations affected by these neglected diseases.

In the case of malaria, there is an additional challenge: treatment must be a single dose, taken orally. “Plasmodium acquires resistance very quickly. We need a drug that can eliminate it in ten days, with a single dose, to get around that problem,” he said.

The panel also featured Monica Cricca, a researcher at UNIBO’s Department of Medical and Surgical Sciences who develops equipment for diagnosing infections. One of her group’s goals is to develop a surveillance system for detecting Candida auris, a superfungus that is resistant to several classes of drugs and capable of causing serious infections.

She said that the pathogen spread throughout Italy during the COVID-19 pandemic, a phenomenon that was also observed in Brazil (read more at: agencia.fapesp.br/36111). “We’re trying to implement a surveillance system to limit its spread,” she said.

The topic of antimicrobial resistance was also addressed by Ana Cristina Gales, professor at the Federal University of São Paulo (UNIFESP) and vice-coordinator of the Antimicrobial Resistance Institute of São Paulo (ARIES Project), supported by FAPESP through the Research, Innovation and Dissemination Centers program (RIDCs).

The panel also included Carmino Antonio de Souza, professor at UNICAMP, vice-president of FAPESP and one of the founders of the Italian-Brazilian Association of Hematology (AIBE), which aims to promote the integration of hematology services in both countries through the exchange of health professionals and the development of clinical and laboratory protocols of common interest.

The discussions were moderated by Bolognesi and Niels Olsen Saraiva Câmara, professor at USP and advisor to FAPESP’s scientific director.