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Pharmacologically controlled neurotrophic factor gene therapy for Parkinson's disease

dc.contributor.advisorKügler, Sebastian Dr.
dc.contributor.authorCheng, Shi
dc.date.accessioned2019-07-24T09:27:39Z
dc.date.available2019-07-24T09:27:39Z
dc.date.issued2019-07-24
dc.identifier.urihttp://hdl.handle.net/21.11130/00-1735-0000-0003-C174-0
dc.identifier.urihttp://dx.doi.org/10.53846/goediss-7576
dc.language.isoengde
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subject.ddc570de
dc.titlePharmacologically controlled neurotrophic factor gene therapy for Parkinson's diseasede
dc.typedoctoralThesisde
dc.contributor.refereeKügler, Sebastian Dr.
dc.date.examination2019-06-25
dc.description.abstractengDuring the PhD thesis, two projects were carried out. In the first project, an inducible AAV-5 vector for expression of GDNF, under control of the approved small molecule drug mifepristone, was evaluated in rats. GDNF expression could be induced over a wide range up to four hundred-fold over endogenous background, and completely returns to baseline within 3 – 4 weeks, without showing any non-induced background expression. Treatment efficacy was evaluated in the 6-OHDA model of PD, where repeated short-term expression of GDNF restored motor capabilities. Pharmacokinetics of Mfp showed unexpected gender-related differences, which were overcome by CYP3A inhibition. In the second project, a “humanized” alpha-1 acid glycoprotein (hAAG) rat model was generated by AAV-1/2-LP1-hAAG intravenous injection. The gene therapy method was tested in the hAAG rat model, and a similar level of expression of GDNF was observed in the model rats and native rats.de
dc.contributor.coRefereeZweckstetter, Markus Prof. Dr.
dc.subject.engParkinson's diseasede
dc.subject.enggene therapyde
dc.identifier.urnurn:nbn:de:gbv:7-21.11130/00-1735-0000-0003-C174-0-7
dc.affiliation.instituteGöttinger Graduiertenschule für Neurowissenschaften, Biophysik und molekulare Biowissenschaften (GGNB)de
dc.subject.gokfullBiologie (PPN619462639)de
dc.identifier.ppn1672306841


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