Spinocerebellar Ataxias (SCAs) are a group of genetically diverse, rare neurodegenerative diseases primarily affecting the cerebellum. They lead to progressive loss of motor coordination, speech difficulties, and other neurological impairments. Despite being monogenic in origin, SCAs display substantial clinical heterogeneity—including variability in age of onset, disease progression, and symptoms—even among individuals with the same mutation. In Portugal, Spinocerebellar Ataxia type 3—also known as Machado-Joseph Disease (MJD)—is particularly prevalent in the Azores, representing the highest prevalence recorded worldwide. As no curative treatment is currently available, this genetic disorder has devastating consequences not only for patients, but also for their families and communities.
In a wider perspective, SCAs are part of the broader category of rare diseases, which collectively affect over 30 million individuals in Europe alone. Yet, due to their low prevalence and high biological diversity, research into rare diseases faces challenges such as lack of funding, data scarcity, and fragmented research communities. Along with these challenges, the limited availability of dedicated computational resources and tools severely hampers the identification of robust biomarkers and the development of targeted treatments across the rare disease landscape.
The SYSSCA project responds directly to these challenges by establishing a translational, systems-level framework for rare disease research, with a focus on SCAs. It will be based on the comprehensive collection and curation of existing disease-associated molecular and clinical data, such as transcriptomics profiles and relevant molecular interaction. Through the application of computational systems biology, artificial intelligence, and experimental validation , SYSSCA strives to achieve the three following aims:
Importantly, the application of advanced systems biology tools will tackle the underlying molecular heterogeneity with different cell types affected to varying degrees in individual patients, so that our approach can open new avenues towards precision medicine for rare diseases.
In addition to its scientific innovation, SYSSCA is deeply committed to open science and community engagement. It will establish AtaxiaConnect, a public web platform for data sharing and visualisation, enabling researchers worldwide to explore and build on the project’s results. SYSSCA aims also to connect with patient advocacy groups, promoting science literacy and ensuring the voices of those affected by SCAs are heard throughout the research process.
By combining methodological innovation, translational research, and stakeholder involvement, our ambition is that SYSSCA not only advances our understanding of SCAs but also establishes a new paradigm for boosting the research in rare diseases.
To this end, the SYSSCA project at the Centre for Innovative Biomedicine and Biotechnology is based on a close collaboration between the Bioinformatics and Data Analytics Unit, and Vectors, Gene and Cell Therapy group, an internationally leading hub of Spinocerebellar Ataxia research.