Next generation gene therapy strategies for treatment of neurodegenerative diseases

Purpose and goal

The purpose of the pilot study was to generate the data necessary for further development of the program towards a clinical trial in this area. It was understood that the the pilot data generated here would be instrumental in obtaining further funds to complete the pre-clinical development phase and perform first-in-man trials.

Results and expected effects

The gene delivery method we use results in local and continuous production of dopamine in the caudate nucleus and putamen where dopamine signalling deficiencies are at the culprit of pathophysiology in Parkinson´s disease. Two enzymes are necessary and sufficient to obtain this outcome. These enzymes (TH and GCH1) enable any brain cell capable of producing DOPA - the precursor to dopamine. This precursor is non-polarized molecule and can be transported across membranes using the large amino acid transporters, where the AADC activity is present DOPA can then be converted to dopamine.

Approach and implementation

We implemented the study by first generating a parkinsonian model in NHP by use of systemic MPTP and later delivered the AAV vectors encoding the above mentioned genes via a stereotaxic surgical procedure, in an analogous way as it is performed in humans undergoing the same surgical procedure for clinical trials. The animals were then followed for several months before the experiment was terminated.