A research carried out at the Carlos Chagas Institute (ICC/Fiocruz Paraná) opens up new perspectives for the treatment of acute lymphoid leukemia (ALL), the most common type of cancer in childhood. The work resulted in patents being granted in China in July 2024 and in the United States in December. The technology is still being analyzed for a patent in Canada, India, and the European Community. The discovery, made by researchers Tatiana Brasil and Nilson Zanchin and PhD student Stephanie Bath de Morais, proposes an innovative version of the human enzyme asparaginase, making the treatment more efficient and less toxic.
Asparaginase has been one of the main drugs used to treat ALL since the 1970s. Currently, the enzyme used in the treatment is extracted from bacteria and, although effective, it causes a strong immune reaction in the body, thus causing side effects. The solution developed by the group from Fiocruz Paraná proposes an alternative with a lower risk of rejection, as it uses a modified version of human asparaginase. "The human version of the enzyme, on its own, does not have enough biochemical activity to be used as a drug. Our study identified structural alterations capable of activating it, thus making it functional for therapeutic purposes," explains Tatiana Brasil.
The project began development in 2013, when Brazil faced the risk of running out of the imported drug. The challenge led the team to investigate possibilities for national production, going beyond simply reproducing the existing drug. "The asparaginase currently used in treatment has been the same since the 1970s, with few advances. Our approach was to modify the human version of the enzyme so that it had a therapeutic effect, minimizing adverse reactions," says Tatiana.
The research revealed that human asparaginase, when produced in the laboratory, initially lacked sufficient activity to degrade asparagine, an amino acid essential for the proliferation of cancer cells. "Our job was to identify and modify specific regions of the enzyme's structure so that it acquired the same therapeutic capacity as its bacterial version, but less likely to cause rejection by the immune system," explains Stephanie Morais.
The impact of the research also extends to the national production of biopharmaceuticals. Today, Brazil imports all the asparaginase used in the Unified Health System (SUS). The new enzyme could enable local production and reduce costs. "With national production, we would be less dependent on imports and could expand access to treatment, particularly benefiting the SUS," says Tatiana.
The path to patent protection was monitored by Fiocruz's Technological Innovation Center (NIT). "From the first positive results, we were already working on a patent application to ensure the intellectual protection of the discovery," Tatiana recalls. Obtaining patents in China and the United States reinforces the innovative nature of the project and could speed up future partnerships for industrial development.
The team is currently working on optimizing the production of the enzyme for pre-clinical tests, conducted in collaboration with the National Cancer Institute (INCA). Moreover, Biomanguinhos, a Fiocruz unit specializing in the production of biopharmaceuticals, is also taking part in the process. "Our goal is to carry out pre-clinical tests to validate the effectiveness of the enzyme and move on to the clinical testing phase," says Stephanie.
The director of Fiocruz Paraná, Stenio Fragoso, highlights the strategic importance of the research for the institution and for public health. "This achievement shows the capacity of the Carlos Chagas Institute to produce scientific innovations with a direct impact on the population. Having an innovative solution to treat childhood leukemia shows the potential of Brazilian science to generate concrete answers to health challenges," he says.
The team's expectation is that the progress made will allow them to speed up testing and, in the future, bring the new asparaginase to the market. "Our enzyme could be a first-line therapeutic alternative for adults, who have a stronger immune response to bacterial asparaginase. The impact could be even greater than we anticipated," concludes Tatiana.
The coordinator of ICC/Fiocruz Paraná's New Business and Innovation Office (ANNI), Fabrícia Pimenta, highlights the institution's ongoing work to value and protect the research carried out. "The granting of these patents reinforces the relevance of national scientific innovation and expands the possibilities for future partnerships to make the new drug viable," she said.