ProSavin a gene therapy approach for Parkinson's disease

L-Dopa has remained the primary standard of care for Parkinson's disease (PD) for the last 40 years. Although highly efficadous in the early stages of disease, it is assodated with debilitating long term side effects, such as dyskine-sias. Therapeutic strategies that aim to provide a constant dopami... Full description

L-Dopa has remained the primary standard of care for Parkinson's disease (PD) for the last 40 years. Although highly efficadous in the early stages of disease, it is assodated with debilitating long term side effects, such as dyskine-sias. Therapeutic strategies that aim to provide a constant dopamine level in the striatum have been hypothesized to provide therapeutic benefits with reduced side effects. We have developed a lentiviral vector (ProSavin) derived from the equine infectious anaemia virus (EIAV) expressing the three key dopamine biosynthetic enzymes (tyrosine hydroxylase, aromatic L-amino acid decarboxylase and GTP cyclohydrolase-1). ProSavin has been demonstrated to mediate dopamine production and cause long term (>2 years) behavioural correction in the gold standard, MPTP non human primate (NHP) model of PD. Further studies have also demonstrated that ProSavin can prevent or reduce dyskinesias in NHP models. A phase I/II clinical trial to evaluate the safety and efficacy in late stage PD patients was initiated in Dec 2007. The trial is designed to evaluate the safety and efficacy profile of ProSavin following bilateral administration to the sensorimotor putamen of mid to late stage PD patients. To date, two dose levels have been evaluated and have been demonstrated to be well tolerated with no serious adverse events reported. In the first cohort of patients that received a low dose of ProSavin a -30% improvement in motor function was observed by 3 months post treatment, as assessed by UPDRS Part III scores, and this was sustained up to 12 months. In the second cohort of patients a similar level of improvement has been observed at 3 months post treatment. A summary of these early clinical results will be presented at the meeting.