Focused-ultrasound mediated anti-alpha-synuclein antibody delivery for the treatment of Parkinson’s disease
2017
Parkinson’s disease (PD) is associated with the selective death of dopaminergic (DA) neurons in the
substantia nigra
pars compacta(SNpc). While the specific cause of the neuronal loss remains elusive, the abnormal accumulation of
alpha synuclein(α-syn), a major constituent of
Lewy bodies, is considered to play a central role in the pathology of PD. Previous studies have shown the potential of immunotherapy with antibodies against α-syn, but such treatments remain ineffective due to the presence of the blood-brain barrier (BBB), which hinders most therapeutic agents to diffuse to the brain parenchyma. Therefore, in this study, we used focused ultrasound (FUS) in conjunction with
microbubblesto transiently and noninvasively open the BBB and deliver anti-α-syn monoclonal antibodies (mAb) to the brains of transgenic PD mouse models. Preliminary histological findings demonstrate that the FUS promotes the delivery of anti-α-syn mAb to the transgenic mice overexpressing the human A53T or A30P α-
synuclein. We ...
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