| dc.contributor.advisor | Kügler, Sebastian Dr. | |
| dc.contributor.author | Cheng, Shi | |
| dc.date.accessioned | 2019-07-24T09:27:39Z | |
| dc.date.available | 2019-07-24T09:27:39Z | |
| dc.date.issued | 2019-07-24 | |
| dc.identifier.uri | http://hdl.handle.net/21.11130/00-1735-0000-0003-C174-0 | |
| dc.identifier.uri | http://dx.doi.org/10.53846/goediss-7576 | |
| dc.language.iso | eng | de |
| dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | |
| dc.subject.ddc | 570 | de |
| dc.title | Pharmacologically controlled neurotrophic factor gene therapy for Parkinson's disease | de |
| dc.type | doctoralThesis | de |
| dc.contributor.referee | Kügler, Sebastian Dr. | |
| dc.date.examination | 2019-06-25 | |
| dc.description.abstracteng | During 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.coReferee | Zweckstetter, Markus Prof. Dr. | |
| dc.subject.eng | Parkinson's disease | de |
| dc.subject.eng | gene therapy | de |
| dc.identifier.urn | urn:nbn:de:gbv:7-21.11130/00-1735-0000-0003-C174-0-7 | |
| dc.affiliation.institute | Göttinger Graduiertenschule für Neurowissenschaften, Biophysik und molekulare Biowissenschaften (GGNB) | de |
| dc.subject.gokfull | Biologie (PPN619462639) | de |
| dc.identifier.ppn | 1672306841 | |