ProSavin: A gene therapy for Parkinson's Disease

Methods: Oral dopaminergic treatment have remained the primary standard of care for Parkinson's disease (PD) for the last 40 years. Although highly efficacious in the early stages of disease they are associated with debilitating long term side effects that seriously impact on the quality of life and restrict the longevity of such treatment. The severity of PD, lack of a cure and the limited long term effectiveness of current therapies allow for the consideration of novel therapeutic approaches. Methods: We have developed a lentiviral vector (ProSavin registered ) derived from the equine infectious anaemia virus (EIAV) expressing the three key dopamine biosynthetic enzymes (tyrosine hydroxylase, aromatic L-amino acid de-carboxylase and GTP cyclohydrolase-1). Results: ProSavin was previously demonstrated to mediate dopamine production and cause behavioural correction in the 6-OHDA lesion rat model of PD (Azzouz et al., 2002). Further studies have demonstrated dopamine replacement and significant long term (>2 years) efficacy in a severe MPTP-lesioned non human primate (NHP) model, following bilateral injection into the sensorimotor putamen. Following these proof of principle efficacy studies a series of preclinical studies has been performed showing that ProSavin is safe and well tolerated in toxicology studies. Conclusion: A phase I/II clinical trial to evaluate the safety and efficacy in late stage PD patients has been approved and was initiated in Dec 2007. The trial will evaluate the safety and efficacy profile of ProSavin following bilateral administration to the sensorimotor putamen. A summary of the translation of the development of ProSavin from the bench to the clinic will be presented.