Summary:Treatments with potential neuroprotective capability for Parkinson's disease (PD) have been investigated in randomized, controlled, clinical trials and other studies since the mid-1980s. Although promising leads have arisen, no therapy has been proven to halt or slow disease progression. Several large-scale studies have highlighted progress in methodology, as well as the frustrations of translating laboratory science to practical applications. This review summarizes findings from clinical trials with several classes of compounds, including monoamine oxidase-B inhibitors (selegiline, lazabemide, rasagiline), dopaminergic drugs (ropinirole, pramipexole, levodopa), antioxidant strategies (␣-tocopherol), mitochondrial energy enhancers (coenzyme Q 10 , creatine), antiapoptotic agents (TCH346, minocycline, CEP-1347), and antiglutamatergic compounds (riluzole). Beyond small-molecule pharmacology, gene therapy approaches, such as delivering neurotrophic substances (e.g., neurturin) by viral vector, are the next generation of treatment options.

Traditional deep brain stimulation requires intraoperative neurophysiological confirmation of electrode placement. Recently, purely image guided methods are being evaluated as to their clinical efficacy in comparison to surgery using microelectrode recordings. We used the ClearPoint(®) system to place electrodes in both the subthalamic nucleus and globus pallidus internus in patients with advanced Parkinson's disease. Off medication UPDRS scores were assessed before and 1 year after surgery as well as pre- and 1 year post-operative neuropsychological outcomes. Targeting precision was also assessed. Patients implanted in the subthalamic nucleus improved by 46.2 % in their UPDRS scores post-operatively (p = 0.03) whereas the globus pallidus group improved by 41 % (p = 0.06). There were no significant adverse neuropsychological outcomes in either group of patients. Mean radial error for the STN group was 1.2 ± 0.7 mm and for the GPi group 0.8 mm ± 0.3 mm. Image guided DBS using the ClearPoint(®)system has high targeting precision with robust clinical outcomes. Our data are in accord with recent studies using the same or similar technologies and provide a rationale for a large comparative study of image-guided versus microelectrode guided DBS.

In our series based on a small sample size, pimavanserin is well-tolerated and effective as both monotherapy and adjuvant treatment for moderate to severe. This medication can facilitate reduction or cessation of DRB medication.