Novel therapies in the treatment of Parkinsons disease

Abstract

Although various effective treatments for Parkinsons disease are available, novel therapies targeting the different pathways that lead to cell dysfunction and death are still required. Some of these pathways that have been implicated so far include mitochondrial dysfunction, oxidative stress, kinase pathways, calcium dysregulation, inflammation, protein handling and prion-like processes. Safinamide, currently in phase III clinical trials for the treatment of PD, is a unique molecule with multiple mechanisms of action and a very high therapeutic index. It combines potent, selective, and reversible inhibition of MAO-B with blockade of voltage-dependent Na+ and Ca2+ channels and inhibition of glutamate release. Several of these proposed newer agents have innovative mechanisms of action (increase mitochondrial biogenesis, reduce apoptosis, upregulation of heat shock proteins, increase endosomal release and uptake of ? synuclein by recipient cells.) Finally, surgical-based approaches such as deep brain stimulation , neuroablative procedures such as thalamotomy and pallidotomy and neural transplantation are other potential treatments. However, technical improvements in these procedure are required to address procedural safety concerns.