Pre-clinical evaluation of the safety and effectiveness of the 5-aminolevulnic acid (5-ala) molecule as a facilitator of surgical glioma resection

• Grant number: 21/09774-5
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): December 01, 2021
• Effective date (End): May 31, 2023
• Field of knowledge: Biological Sciences - Pharmacology - General Pharmacology
• Principal Investigator: Catarina Raposo Dias Carneiro
• Grantee: Thayná Fernanda Fonseca
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

Gliomas account for approximately 80% of primary malignant brain tumors in adults. The highly infiltrating and aggressive glioblastoma subtype (grade IV) corresponds to an average patient survival around 15 months after diagnosis. Advances in knowledge of new therapeutic options have not yet significantly improved the survival of these patients, who are currently treated using surgical resection, adjuvant radiotherapy and chemotherapy. Currently, the degree of surgical resection corresponds to the main prognostic factor, providing greater overall survival for patients who underwent surgical resection greater than 78% of the tumor area. Despite advances, the difficulty of the neurosurgeon in distinguishing the borderline margins corresponding to the tumor portion from healthy brain tissue is still a major challenge. In this sense, fluorescence-guided surgery for malignant gliomas, using 5-aminolevulinic acid (5-ALA), has become the gold standard in several countries. 5-ALA, administered to the patient prior to surgery, produces fluorescence in the tumor portion, detectable using an appropriate device, allowing assistance during the resection of malignant gliomas by facilitating the visualization of the tumor area in relation to the healthy tissue margin. Despite the benefits, the cost of using the method, both in relation to the production value of the 5-ALA substance, as well as the purchase of specific equipment for its visualization, are inaccessible for a large part of the population, especially in public health systems in developing countries, such as Brazil. In this sense, this project is part of an investigative line that comes from a partnership between researchers from the Faculty of Pharmaceutical Sciences (FCF/UNICAMP) and the neurosurgery team of the Hospital da Irmandade da Santa Casa de Misericórdia of São Paulo, which aims to produce and synthesize 5-ALA by a low-cost route and with national technology, to be administered to patients in the Unified Health System (SUS). Within this greater objective, the analyzes of this project will constitute the pre-clinical stages of the study, evaluating the safety and efficacy of 5-ALA synthesized in FCF in a murine model. The project aims to assist in the development of a low-cost compound that is viable for use in SUS patients, contributing to a good prognosis and an increase in the quality of life of these patients. (AU)