Aproveitar a biologia dos sistemas para compreender melhor as ataxias espinocerebelares e identificar novos tratamentos: um paradigma para as doenças raras

The SYSSCA project is structured around five core scientific objectives (O1-O5) dedicated to advancing research on Spinocerebellar Ataxias (SCA), along with an aim to broaden the impact within the rare diseases research field: O1: Uncover both common and unique molecular signatures that mark the onset and progression of SCA1, SCA2, and SCA3. O2: Detect new biological modifiers for SCA and confirm their effects using in vitro models. O3: Discover prospective drugs addressing SCA-specific disease mechanisms and substantiate their effectiveness through in vitro validation. O4: Develop an accessible repository for omics data related to SCA: AtaxiaConnect O5: Create and deploy data integration and analysis pipelines adaptable for researching rare diseases, evaluating their effectiveness in practical applications. Moreover, SYSSCA endeavours to engage patient communities and the general public with the following objective: O6: Educate patients and the public about the complexities and diversity of the biology underpinning SCAs, aiming to enhance understanding and support for affected individuals. CHALLENGES ADDRESSED BY SYSSCA The SYSSCA project directly tackles several critical challenges in the field of SCAs. Firstly, it addresses the urgent need for a comprehensive understanding of the molecular mechanisms underlying SCAs, characterized by significant heterogeneity and complex pathophysiology. Secondly, SYSSCA seeks to overcome the current void in effective treatments by employing drug repurposing strategies to discover existing drugs that could offer new therapeutic avenues for SCA patients. Thirdly, it addresses the lack of personalised treatment options by identifying unique and common molecular signatures, biological modifiers, and biomarkers that could enable tailored treatment approaches. Additionally, the creation of AtaxiaConnect for SCA represents a significant step towards fostering open scientific collaboration and data sharing, addressing the challenge of data sharing and integration in rare disease research. Therefore, the proposed research is highly relevant, targeting fundamental obstacles in understanding and treating SCAs. SYSSCA GOES BEYOND THE STATE OF THE ART The objectives set by SYSSCA push the boundaries beyond the current state of the art. The multidisciplinary approach, blending bioinformatics, systems biology tools, machine learning, artificial intelligence and experimental validation, represents a leap forward in rare disease research, a field that has often been neglected in biomedical investigation. Furthermore, the ambition to create AtaxiaConnect as a dynamic tool for data visualization and analysis, alongside the development of analysis pipelines for broader rare disease research applications is aiming at bridging current gaps in the research field. Hence, SYSSCA's objectives propose a novel blueprint for rare disease research, emphasizing integration, innovation, and interdisciplinary collaboration.