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Parkinson's disease: what will the future bring?

John Hardy

Introduction

Predicting the future is a notorious a way to ensure that you appear foolish in 20 years’ time. However, it is now more than 50 years since the discovery of the effects of levodopa in reserpin- ized (dopamine-depleted) animals and nearly 50 years since the first human levodopa treatment trials [1]. Hence it is perhaps worth taking stock of progress and thinking about how things might progress from here.

Since the miracle of dopamine replacement therapy, there has been incremental improvement in the pharmacological treatment of Parkinson’s disease (PD), first with peripheral decarboxylase inhibition and then dopamine agonists [2]. Surgical therapies, too, had initially startling clinical effects, and have subsequently shown steady progress [3]. Neither current medical nor surgical interventions are believed to have any effects on the progression of the neurodegenerative process. In early disease, initial therapy leads to remarkable benefits. Indeed, dopaminergic therapy has more than doubled the life expectancy of patients after their diagnosis [4].

Despite this I am sure that the current situation leads to great frustration among patients and caregivers. In nearly all other neurodegenerative diseases, patients get the diagnosis, for example Alzheimer’s disease (AD), motor neuron disease, or Huntington’s disease, and are told, at diagnosis, that there is no effective treatment to halt disease progression. While this is a cruel outcome, there is no arguing with it. Currently, there are no effective treatments for these diseases and patients and their families cope with that outcome as best they can. With PD, early treatment really is miraculous and, for a period of a few years, it allows patients and their families to return to a near-normal life. Yet the effectiveness of this treatment gradually and frustratingly lessens and the disease gains the upper hand, finally leading to disability and death in a manner no less unpleasant than that caused by the less-teasing diseases which have no treatment at all. It must seem to patients and caregivers that we are close to ‘curing’ the disease, and yet, of course, we are not.

Since it seems likely that only incremental improvements are going to be made through either further advances in dopaminergic drugs or surgical treatment, clearly we need to make substantive progress towards either preventing the disease or in mechanistic therapy. It is in this area that we have to hope we can make progress.

 
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