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Article Abstract
Objective: Gene therapy by convection-enhanced delivery of type 2 adeno-associated virus-glial cell derived neurotrophic factor (AAV2-GDNF) to the bilateral putamina seeks to increase GDNF gene expression and treat Parkinson's disease (PD).
Methods: A 63-year-old man with advanced PD received AAV2-GDNF in a clinical trial. He died from pneumonia after anterior cervical discectomy and fusion 45 months later. An autopsy included brain examination for GDNF transgene expression. Putaminal catecholamine concentrations were compared to in vivo F-Fluorodopa (F-FDOPA) positron emission tomography (PET) scanning results before and 18 months after AAV2-GDNF infusion.
Results: Parkinsonian progression stabilized clinically. Postmortem neuropathology confirmed PD. Bilateral putaminal regions previously infused with AAV2-GDNF expressed the GDNF gene. Total putaminal dopamine was 1% of control, confirming the striatal dopaminergic deficiency suggested by baseline F-DOPA-PET scanning. Putaminal regions responded as expected to AAV2-GDNF.
Conclusion: After AAV2-GDNF infusion, infused putaminal regions showed increased GDNF gene expression, tyrosine hydroxylase immunoreactive sprouting, catechol levels, and F-FDOPA-PET signal, suggesting the regenerative potential of AAV2-GDNF in PD.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11341257 | PMC |
| http://dx.doi.org/10.1002/mds.29820 | DOI Listing |
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