Recent developments in the treatment of Parkinson's Disease

Abstract

Parkinson's disease (PD) is a common neurodegenerative disease typified by a movement disorder consisting of bradykinesia, rest tremor, rigidity, and postural instability. Treatment options for PD are limited, with most of the current approaches based on restoration of dopaminergic tone in the striatum. However, these do not alter disease course and do not treat the non-dopamine-dependent features of PD such as freezing of gait, cognitive impairment, and other non-motor features of the disorder, which often have the greatest impact on quality of life. As understanding of PD pathogenesis grows, novel therapeutic avenues are emerging. These include treatments that aim to control the symptoms of PD without the problematic side effects seen with currently available treatments and those that are aimed towards slowing pathology, reducing neuronal loss, and attenuating disease course. In this latter regard, there has been much interest in drug repurposing (the use of established drugs for a new indication), with many drugs being reported to affect PD-relevant intracellular processes. This approach offers an expedited route to the clinic, given that pharmacokinetic and safety data are potentially already available. In terms of better symptomatic therapies that are also regenerative, gene therapies and cell-based treatments are beginning to enter clinical trials, and developments in other neurosurgical strategies such as more nuanced deep brain stimulation approaches mean that the landscape of PD treatment is likely to evolve considerably over the coming years. In this review, we provide an overview of the novel therapeutic approaches that are close to, or are already in, clinical trials.

Keywords: α-synuclein; deep brain stimulation; drug repurposing; immunotherapies; gene therapies; neural grafting; Parkinson’s disease.

Figure 1.. Putative disease-modifying therapies for PD.

An expanding number of drugs are being considered for their ability to influence the pathogenic processes of PD. These include novel agents and technologies, such as active and passive immunisation and RNA interference techniques to limit the propagation, and synthesis, of α-synuclein. Additionally, several drugs used for other conditions are of interest for potential use in PD given their ability to influence pathways such as the lysosome–autophagy system, mitochondrial function, and neuroinflammation, for example. Abbreviations: α-syn, α-synuclein; ASO, anti-sense oligonucleotide; GCase, glucocerebrosidase; PD, Parkinson’s disease; RNA, ribonucleic acid; UDCA, ursodeoxycholic acid.