Head of Clinical Research Bonn;
Director of the Department of Neurology, University Hospital Bonn; Group Leader
Ataxias denote degenerative disorders of the cerebellum and spinal cord. We are performing large clinical studies that have the goal to build the basis for performing clinical trials. In an ongoing study of 300 risk persons for dominantly inherited spinocerebellar ataxia we found earliest functional abnormalities in mutation carriers up to 20 years before ataxia onset. In a long-term natural history study of more than 500 patients we quantitatively defined disease progression and identified factors that determine progression. Our biomarker work involves MRI studies, movement recording and measurements of biochemical markers. We completed an investigator-initiated phase III trial with acetylleucine.
The locus coeruleus which is the source of forebrain noradrenergic innervation undergoes early degeneration in Alzheimer's disease (AD). We have established a number of behavioral and phyiological paradigms which are supposed to be correlates of the functionality of the locus coeruleus-norepinephrine system. Studies in AD patients showed consistently diminished physiological responses in these paradigms. In order to demonstrate that they depend on noradrenergic transmission we currently perform a study with the ß-receptor antagonist propranolol in healthy subjects. The final goal is to use these paradigms as outcome markers in early clinical trials of noradrenergic compounds.
To better understand the functional interaction beween neocortex and hippocampus during memory formation, we are using electrical stimulation to modulate memory functions and ameliorate declining memory functions in patients with memory deficits. Current work is characterizing the phase synchronization of prefrontal and parietal regions during successful associative memory formation. This will provide a basis for further investigation of manipulating the phase synchronization of prefrontal and parietal regions using electrical stimulation and its impact on associative memory formation and subsequent memory performance.