Section Days abstract book 2010.indd - RUB Research School ...

LS_12
Neuroprotective autoimmunity: Efficacy of glatiramer
acetate in neurodegeneration
Christiane Reick ,1,2 , Gisa Ellrichmann 1 , Carsten Saft 1 , Ralf Gold 1 , Ralf Linker 1
1 Department of Neurology, St. Josefs Hospital, Ruhr-University Bochum, Germany
2 International Graduate School of Neuroscience, Ruhr-University Bochum, Germany
e-mail: Reick.Christiane@rub.de
Background: Glatiramer acetate (GA) is an immunmodulator licensed for the treatment of
relapsing remitting multiple sclerosis and possibly exerts neuroprotective actions via the
induction of neurotrophins like brain derived neurotrophic factor (BDNF). As a model disease
for primary neurodegeneration, R6/2 mice mimick many aspects of Huntington´s disease
(HD) where the formation of huntingtin aggregates may lead to subsequent neuronal loss.
Methods: 3-4 week old female R6/2 mice were immunized subcutaneously GA in complete
Freud´s adjuvant (CFA), or as controls with ovalbumin or with myelin oligodendrocyte
glycoprotein peptide 35-55 (MOG) in CFA. Mice were weighed daily and clinically
monitored to obtain survival curves. Motor impairment was evaluated by accelerating rotarod
and by assessing the clasping score. Histological analyses as well as quantitative RT-PCR
were performed.
Results: In the R6/2 mouse model GA prevents weight loss over the clinical course.
Moreover, both regimens led to a prolonged survival. At the same time, immunization with
GA and MOG led to an attenuated motor impairment as measured by the clasping score and
also in a rotarod analysis. Blinded quantification of neuronal densities in the motor cortex and
the basal ganglia will elucidate underlying mechanisms of protection.
Conclusion: Treatment with GA and immunization with MOG ameliorate the disease course
in a model of HD. Our data speak for the functional relevance of the concept of
neuroprotective autoimmunity and underline the neuroprotective capacity of GA therapy.