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Start of funding 01.01.2010
Transcranial high focused ultrasound (HiFU) as a neuroprotective treatment in Parkinson's disease
Prof. Dr. Jochen Klucken
Friedrich-Alexander-University of Erlangen-Nuremberg
Division of Molecular Neurology
Dr. med. Thilo Hölscher
University of California, San Diego
Department of Radiology and Neurosciences
Parkinson disease (PD) is the second most common neurodegenerative disorder and characterized by resting tremor, muscular rigidity, hypokinesia and postural instability. Histopathological analysis reveals depletion of dopaminergic neurons as well as alpha-synuclein containing eosinophilic intracytoplasmic inclusions (Lewy bodies) in neurons of the substantia nigra and other brain regions. Alpha-Synuclein aggregation can be reduced by overexpressing heat shock proteins (HSP) like Hsp70 in vivo and in vitro models of PD. Recently, it was demonstrated that local Hsp70 expression can be induced using high-focused ultrasound (HiFU) by causing thermal cell stress in vivo. The rationale of the proposed project is to locally induce the expression of chaperone protein Hsp70 in the brain of human alpha-synuclein transgenic mice using transcranial high-focused ultrasound in a non-invasive and non-drug related approach. We will test the hypothesis if the expression of Hsp70 in the brain can be induced using HiFU. In a second step alpha-synuclein transgenic animals will be insonated to study the neuroprotective effect and functional improvement by HiFU. This project, translating basic research into preclinical application will be the initiation of a cooperation between the Divison of Molecular Neurology, University of Erlangen, Bavaria and the Brain Ultrasound Research Lab, the Experimental Neuropathology Laboratory at the University of California, USA.