Multi-user equipament approved in the grant 2024/09684-4: gas chromatography and mass spectrometry system

• Grant number: 25/15867-7
• Support Opportunities: Multi-user Equipment Program
• Start date: October 01, 2025
• End date: September 30, 2032
• Field of knowledge: Biological Sciences - Pharmacology - General Pharmacology
• Principal Investigator: Luiz Claudio Di Stasi
• Grantee: Luiz Claudio Di Stasi
• Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil
• Associated research grant: 24/09684-4 - Preclinical and clinical trial of Musa spp AAA and prediction of treatment response and outcome of Inflammatory Bowel Disease by artificial inteligence: a potential model for other chronic non-communicable diseases, AP.TEM

Abstract

Inflammatory Bowel Disease (IBD) and other non-communicable diseases (NCDs) are responsible for 73.4% (4.1 million people) of annual deaths on the planet. NCDs involving a global burden of economic looses (2011 to 2030) estimated at 47 trillion dollars (5% of gross global product) and so recognized as one of the current biggest global problems. These diseases share, in their etiology and pathophysiology, the processes of oxidative stress, dysbiosis of the intestinal microbiota, and failures in the autophagy machinery. This way, a product with ability to modulate these three processes can represent a complementary therapy for the treatment of IBD with potential application for other NCDs. Pre-clinical and clinical studies carried out by the proponent group (thematic project) with Musa spp AAA, demonstrated that this product has important intestinal anti-inflammatory activity in experimental models and in patients with ulcerative colitis (UC), one of the manifestations of IBD in humans. Musa spp AAA acted as intestinal anti-inflammatory products, mainly increasing the short-chain fatty acids production and improving the intestinal microbiota composition and diversity. Moreover, Musa spp AAA positively modulated several autophagy biomarkers due to presence of trehalose in its composition, one of the most important molecules able to modulate autophagy processes. Based on this, the research project proposes to select (from 8 products) and chemically and pharmacologically standardize a pharmaceutical formulation containing Musa spp AAA, by carrying out studies of i. proof-of-concept studies, including analyzes of gut microbiota modulation, oxidative stress (in vitro analyses), and markers of inflammation (cellular culture models); ii. Preclinical evaluation of efficacy (intestinal anti-inflammatory activity), safety (Brazilian Health Surveillance Agency rules and procedures), pharmacokinetic evaluation (gastric retention, orocecal and ororetal transit time, and others) and the effects of selected pharmaceutical formulations on the organoids of intestinal biopsies from ulcerative colitis patients, and iii. Clinical trial with the best pharmaceutical formulation on the active ulcerative colitis patients. In addition, considering severity of the disease, lack of definitive pharmacological cure, and guidelines of the World Health Organization that points to the urgent need to establish strategies for early detection and prediction of several factors associated with NCDs, the project proposes to develop models based on artificial intelligence that assist the differential diagnosis of UC and CD and allow prediction of response to different treatments and outcome of IBD. Therefore, the expectation of the project is to standardize a complementary therapy for IBD and create prediction tools that help to control this disease. Both actions would unequivocally reduce the impact of this disease on patients' life quality and public health services. Furthermore, this project can be an applicable model for other NCDs, which share the same etiological and pathophysiological factors, such as obesity, diabetes, neurodegenerative diseases and others. Combined with the low production cost and pharmacological efficacy, an only product with several mechanisms of action could represent a major advance in the control of IBD and other NCDs. (AU)