Research focus
Research focus is to develop, refine and apply data-driven approaches to better understand the disease course of spinocerebellar ataxias. The work is based on longitudinal studies of large cohorts of patients and risk persons, and the development of new biomarkers and digital outcome measures. The ultimate goal is to lay the foundations for meaningful therapeutic and preventive trials in spinocerebellar ataxias.
Digital assessment of movement disorders
Clinical scales are currently the mainstay of clinical assessment in movement disorders. However, they lack objectivity and require a hospital visit. To address these problems, we developed a video-based instrument for assessment of ataxia, SARAhome, that is applied by patients at home and allows to assess ataxia severity in a more representative manner than by conventional scoring during hospital visits. This work is currently extended by development of AI-based automatic scoring methods for gait and speech.
MRI markers of ataxias
MRI is extensively used to study brain morphology in ataxia. With the goal to establish and validate MRI markers as outcomes in clinical trials, we are developing new acquisition and evaluation methods, and are performing large-scale studies in ataxia patients and risk persons. In the JPND-funded SCAIFIELD project, we are establishing ultra-high field MRI biomarkers for ataxias for detecting early disease manifestation and monitoring progression. To facilitate data analysis, we developed and validated CerebNet, a fully automated, AI-based method for the lobular segmentation of the cerebellum, including the separation of gray and white matter. In a JPND-funded MRI study of >250 spinocerebellar ataxia type 3 (SCA3) mutation carriers, we provided evidence that brain and spinal cord tissue loss started >10 years before ataxia onset. Pontine volume appeared to be the most promising imaging biomarker candidate for interventional trials. In parallel NIH-funded studies, we are exploring the potential of MRI diffusion and spectroscopy markers.
Patient-reported, health economic and psychosocial outcomes in ataxias:
Goal of the EJP RD-funded PROFA project is to gain in-depth insights into the everyday life of ataxia patients. To this end, we are acquiring patient-reported, health economic, and psychosocial data in real time using an e-health app. This study provides a comprehensive understanding of the economic, humanistic and societal burden of ataxia and identifies determinants of health and social life and efficient use of healthcare resources, which is crucial to improve treatment, care, and everyday life of ataxia patients and their families.
Staging models of spinocerebellar ataxias (SCAs)
Although neurodegenerative diseases, such as SCAs, evolve in a single continuous disease process, staging models are assumed essential for stratification and enrolment in clinical trials. In the framework of the JPND-funded ESMI project, we developed the first data-driven staging model of SCA3 that includes an initial asymptomatic carrier stage followed by the biomarker stage characterized by absence of ataxia, but changes of NfL, as well as pons and cerebellar white matter volumes, finally leading into the ataxia stage, defined by manifest ataxia. These data open up the intriguing view on future preventive trials in non-ataxic patients.
Natural history and biomarker evolution of sporadic ataxias
Sporadic adult-onset ataxias without known genetic or acquired cause are subdivided into multiple system atrophy (MSA) and sporadic adult-onset ataxia of unknown etiology (SAOA). To fill knowledge gaps about clinical evolution and biomarker characteristics of sporadic ataxias, we established the SPORTAX registry that includes >500 participants. SPORTAX data provided detailed information on differential evolution and prognostic relevance of biomarkers in MSA and SAOAi.