Manuela Lima

I developed the research for my Doctorate in the area of Human Genetics, with the study of a neurodegenerative disorder, Machado-Joseph disease(MJD)/Spinocerebellar ataxia type 3 (SCA3). This effort (undertaken as part of a multidisciplinary group of researchers/clinicians that has been working in the Azores for over 20 years) has provided the availability of data concerning the Azorean MJD families, from which molecular-oriented research on MJD has emerged. The extensively studied Azorean pedigrees have allowed the development of studies on several aspects of this disease, which have been developed under my coordination. Previous research has studied aspects of the historical genetics and epidemiology of SCA3, molecular mechanisms (such as alternative splicing), patterns of transmission, particular clinical presentations, genetic modifiers and, more recently, molecular biomarkers. In SCA3 the incomplete explanation of age at onset provided by the CAG repeat size shows that other factors, namely genetic, are involved in the disease. The knowledge of such factors should allow a better prediction of onset and the improvement of prognosis. Although no therapeutic strategies to delay or reverse SCA3 morbidity are currently available, disease-modifying compounds have started to be identified and there is an urgent need to find molecular biomarkers which can be able to monitor disease progression and detect subtle therapeutic benefits. The identification of novel transcriptional biomarkers of the disease is a nuclear core of our research. The particular epidemiological situation of the Azores with respect to MJD justifies the close collaboration between researchers and patients, namely thru the “Associação Atlântica de Apoio ao doente de Machado-Joseph” a non-profit patients organization that has been playing a fundamental role in the Azores, aiding also patients in many places of the world. We are currently taking part in the European Network ESMI, a project that aims to establish the largest trial-ready cohort of MJD patients.