Abstract
Animal models towards understanding and treating Parkinson’s disease (PD) are important translational steps toward clinical applications.
The Göttingen minipig(GM), fits progressional neurological models due to an relative low adult weight between 20-40 kg, and has a large gyrencephalic brain (6x 5 x 4 cm) that can be examined at sufficient resolution using both conventional clinical scanning modalities and preclinical testing of deep brain stimulation, stem cell grafting and other neuromodulatory devices.
Aim:
Using inoculating of human or pig alpha-synuclein(aSYN) fibrils or overexpressing aSYN using Lenti virus(LV) and Adeno Assosiated Virus(AAV) vectors in the nigrostriatal system, we hope to create a new porcine model for PD.
Methods:
Using conventional human-intended stereotaxic neurosurgery methods, we apply aSYN in the catecholamine nigrostriatal system of 13 GM.
The changes are quantified by neurological tests (behavior, scoring and gait), conventional and preclinical PET scanning modalities, autoradiography and post mortem histological evaluation.
Results:
Studies are still ongoing and data is being collected. First results from LV methods shoved "prove of concept" on gait and histology. Evaluation of gait, PET, autoradiography and histology are ongoing on AAV-models and awaiting on inoculation fibril-models.
Discussion:
We predict that these animal models will be useful and beneficial in the understanding of pathological mechanisms of human PD, novel therapeutic strategies such as antiaggreganttreatment, induced pluripotent stem cells or immunotherapy and development of novel radioligands for early diagnosis and assess disease progression.
The Göttingen minipig(GM), fits progressional neurological models due to an relative low adult weight between 20-40 kg, and has a large gyrencephalic brain (6x 5 x 4 cm) that can be examined at sufficient resolution using both conventional clinical scanning modalities and preclinical testing of deep brain stimulation, stem cell grafting and other neuromodulatory devices.
Aim:
Using inoculating of human or pig alpha-synuclein(aSYN) fibrils or overexpressing aSYN using Lenti virus(LV) and Adeno Assosiated Virus(AAV) vectors in the nigrostriatal system, we hope to create a new porcine model for PD.
Methods:
Using conventional human-intended stereotaxic neurosurgery methods, we apply aSYN in the catecholamine nigrostriatal system of 13 GM.
The changes are quantified by neurological tests (behavior, scoring and gait), conventional and preclinical PET scanning modalities, autoradiography and post mortem histological evaluation.
Results:
Studies are still ongoing and data is being collected. First results from LV methods shoved "prove of concept" on gait and histology. Evaluation of gait, PET, autoradiography and histology are ongoing on AAV-models and awaiting on inoculation fibril-models.
Discussion:
We predict that these animal models will be useful and beneficial in the understanding of pathological mechanisms of human PD, novel therapeutic strategies such as antiaggreganttreatment, induced pluripotent stem cells or immunotherapy and development of novel radioligands for early diagnosis and assess disease progression.
| Originalsprog | Dansk |
|---|---|
| Publikationsdato | 2015 |
| Status | Udgivet - 2015 |
Emneord
- AU HEALTH PHD DAY 2015