A main focus of the working group is the bidirectional translation between basic research and clinical patient work, including patient-derived iPS cultures, in particular hypothesis-driven work to understand the underlying molecular pathophysiology. The overall aim is to pursue pathophysiology-based drug development and biomarker development (wet markers, MRI markers, PET markers and behavioural endophenotypes), characterisation of prodromal states of neurodegeneration and clinical correlation of the spread of disease pathology including non-motor symptoms in neurodegenerative diseases. These also include the characterisation of brain reserve, the interaction of cognitive reserve in motor neurodegenerative diseases and motor reserve in cognitive neurodegenerative diseases. Future directions will increasingly include work on healthy and pathological ageing, including modes and mechanisms of disease transformation from prodromal stages or interventions to prevent secondary ageing.

Clinical research

The group is an active partner in several prospective registry studies of the DZNE and head of the DESCIBE-ALS cohort. The group continuously participates in clinical phase 1-3 trials of new therapies for neurodegenerative diseases, including studies with antisense oligonucleotides (ASOs).

Palliative and patient-centered care in advanced neurodegeneration

Patient-centered care is another focus of our group also involving joint activities within DZNE (e.g. Interside project of next-of-kins studies of FTD patients, PROSA Study: ‘Diagnostic and Prognostic Digital Speech Biomarker with Low Patient Burden to Improve Future Clinical Studies in ALS and FTD Patients). Using computer-based communication techniques including eye-tracking systems we investigate the Quality of Life (QoL) of such advanced patients and the influence of health care and public mains on the QoL of patients and their next of kins as well as the influence on decision making towards live prolonging procedures.

Human cell models of neurodegeneration

The basic science DZNE group focus on the establishment of a resource of hypothesis-matched cell models: a panel of primary cells (fibroblasts) and patient-specific iPS cells together with improved protocols for the derivation of disease-relevant cell types, ideally from patients from whom clinical data, biomaterials (cerebrospinal fluid, blood, urine, imaging) and post-mortem tissue are available as well. Molecularly, we are particularly concerned with the interaction of different cellular organelles, mitochondrial/energy (dys)metabolism and axonopathy, DNA damage/retrotransposon activation and cell-intrinsic immune response to the latter. The focus is on ALS/FTD (in particular FUS-ALS), but further neurodegenerative diseases (HD, PD, VPS13inopathies) have become further important areas of basic research of our group. Beside the “reverse translation” (from clinic to basic research), we pursue the aim of “forward translation” with regard to drug screening/development and improved diagnostic procedures with the main focus on unraveling the pathophysiology of the underlying neurodegenerative disease.