Author for correspondence: Cambridge Centre for Brain Repair & the Department of Neurology, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK Tel.: +44 1223 331160 Fax: +44 1223 331174 rab46@cam.ac.uk have received levodopa for more than 5 years, in 80% of patients treated for 10 years, and in nearly all patients with young-onset disease. In a bid to control these motor fluctuations, patients’ therapy may need to be escalated to include more intensive pharmacotherapies such as infusions of subcutaneous apomorphine and jejunal Duodopa infusions. In addition, deep brain stimulation (DBS) surgery, either of the subthalamic nucleus or the globus pallidus pars interna, can be useful for treating PD patients at this stage when the motor fluctuations and dyskinesias cannot be adequately managed with pharmacological manipulation. The 5-year follow-up of patients who have received bilateral stimulation of the subthalamic nucleus in PD clearly shows that their improvement in motor function is sustained over time. However, disability still progresses from year to year, indicating ongoing degeneration in both dopaminergic and nondopaminergic sites. Furthermore, DBS is also associated with significant cognitive and psychiatric side effects, including severe depression, impulsivity and apathy, all of which may help explain the discrepancy between changes in quality-of-life assessment and motor disability in patients having had this therapy [3]. None of the currently available therapies for PD can slow or halt the disease progression. Therefore, there is a clear need for new therapies in PD that not only are capable of providing dopamine replacement more effectively, but also serve to replace or protect the substantia nigra pars compacta dopamine neurons from further degeneration. In a bid to meet this clinical challenge, novel therapeutic approaches have evolved over the last 20 years, which include a variety of gene therapy approaches, neurotrophic factor delivery and cell replacement therapies. Three main strategies under investigation using gene transfer for targeted protein expression include: “...it has to be realized that cell therapies are not a cure for Parkinson’s disease...” What is the most promising treatment for Parkinson’s disease: genes, cells, growth factors or none of the above?