Upcoming treatments in Parkinson's disease, including gene therapy

SummaryProgress is being made in the development of three categories of therapy for Parkinson's disease: (1) Symptomatic, (2) Neuroprotective, (3) Neurorestorative. Evolving approaches to symptomatic therapy, already in clinical trials, include the use of adenosine 2A antagonists, novel glutamate antagonists, and serotonin receptor antagonists, the latter for the therapy of Parkinson's psychosis and/or levodopa-induced dyskinesias. Examples of promising neuroprotective therapies under evaluation include the administration of creatine, urate-inducing compounds, calcium channel blockers, and pioglitazone, a peroxisome proliferator-activated receptor agonist. Cell-based restorative therapies are not the subject of this presentation, but various forms of gene therapy have shown promise in human Parkinson's disease trials. These protocols typically involve gene transfer into the CNS through the use of viral vectors. Currently, the most advanced studies of this technique involve delivery of an adeno-associated viral vector encoding glutamic acid decarboxylase into the subthalamic nucleus. This treatment has shown modest benefit in early clinical trials. Other gene therapies, in various stages of human clinical trials, include gene transfer for the production of trophic factors, for aromatic amino acid decarboxylase alone, and most recently, a lentiviral vector transfer of an enzymatic dopamine “factory” consisting of three essential enzymes required for production for this neurotransmitter.