INTR10

Authors:

Wenning GK, Koellensperger M, Stefanova N

Institutions:

Department of Neurology
University Hospital
Anichstrasse 35
6020 Innsbruck
AUSTRIA

Title of abstract : Towards neurotransplantation in MSA: preclinical evidence

Abstract text:

Multiple system atrophy (MSA) is a fatal degenerative disorder characterized by a unique oligodendrogliopathy with cytoplasmic alpha-synuclein inclusions and secondary neuronal loss affecting striatonigral and olivopontocerebellar projections as well as central autonomic nuclei. MSA patients typically develop autonomic failure combined with L-dopa unresponsive parkinsonism (MSA-P) reflecting striatonigral degeneration or less commonly cerebellar ataxia (MSA-C). Median survival is 8-9 years regardless of presentation. Due to the lack of effective drugs targeted cell therapy involving striatal repair has been attempted to improve the response to dopaminergic stimulation. Embryonic grafts implanted into the striatum survive in the presence of oligodendroglial synuclein inclusions in a transgenic MSA model. However, more recent data show the formation of synuclein inclusions within grafted tissue. Whether this represents host-to-graft propagation as discussed in recent reports on Lewy body formation within human dopamine grafts remains to be elucidated. Functional grafts effects have sofar only been studied in a unilateral double lesion MSA-P rat model based on sequential administration of 6-OHDA and quinolinic acid into the MFB and lateral striatum. Earlier work from our group suggests that rotational responsivity to apomorphine can be restored using embryonic striatal grafts in the rat model. In contrast, more recently, striatal grafts were only partially superior to sham grafts in restoring L-Dopa responsivity of parkinson-like motor behaviour. Further work is required to define the scope of striatal cell therapy in MSA. At best it may be regarded a palliative approach improving motor function for a number of years. Complementary neuroprotective therapies will be required at the same time.

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