MSA and neurotransplantation

Multiple system atrophy (MSA) is a neurodegenerative disorder that occurs sporadically and causes parkinsonism, cerebellar, autonomic, urinary and pyramidal dysfunction in many combinations. Progressive L-Dopa-unresponsive parkinsonism due to underlying striatonigral degeneration dominates the clinical syndrome in the majority of cases (MSA-P subtype). MSA-P is characterized pathologically by striatonigral degeneration (SND), i.e. degenerative changes in somatotopically related areas of the substantia nigra pars compacta and of the putamen and caudate nucleus. Furthermore, oligodendroglial cytoplasmic inclusions (GCIs) are observed throughout the cortico-striato- pallido-cortical loops and may contribute to the basal ganglia dysfunction. Since pharmacological treatment provides poor symptomatic relief the search for alternative therapeutic approaches such as neurotransplantation is highly justified. Restoration of damaged striatal neuronal circuits by embryonic striatal grafts has been shown in previous preliminary studies to regenerate apomorphine-induced circling behaviour in a double lesion rat model of MSA-P. In the present proposal we will extend this work by systematically evaluating the pattern of behavioural recovery induced by embryonic striatal grafts in both the double lesion rat model as well as a novel transgenic mouse model of MSA. These experiments are expected to pave the way towards neurorestorative therapies for the human disease MSA.

Multiple system atrophy (MSA) is a neurodegenerative disorder that occurs sporadically and causes parkinsonism, cerebellar, autonomic, urinary and pyramidal dysfunction in many combinations. Progressive L-Dopa-unresponsive parkinsonism due to underlying striatonigral degeneration dominates the clinical syndrome in the majority of cases (MSA-P subtype). MSA-P is characterized pathologically by striatonigral degeneration (SND), i.e. degenerative changes in somatotopically related areas of the substantia nigra pars compacta and of the putamen and caudate nucleus. Furthermore, oligodendroglial cytoplasmic inclusions (GCIs) are observed throughout the cortico-striato- pallido-cortical loops and may contribute to the basal ganglia dysfunction. Since pharmacological treatment provides poor symptomatic relief the search for alternative therapeutic approaches such as neurotransplantation is highly justified. Restoration of damaged striatal neuronal circuits by embryonic striatal grafts has been shown in previous preliminary studies to regenerate apomorphine-induced circling behaviour in a double lesion rat model of MSA-P. In the present proposal we will extend this work by systematically evaluating the pattern of behavioural recovery induced by embryonic striatal grafts in both the double lesion rat model as well as a novel transgenic mouse model of MSA. These experiments are expected to pave the way towards neurorestorative therapies for the human disease MSA.