A drug used to treat diabetes has shown promising effects in an innovative Parkinson's disease trial.
In recent years, evidence has been accumulating that the hormone glucagon-like peptide-1 might be a good target for Parkinson's disease. Furthermore, a drug targeting GLP-1, exenatide, a derivative of a compound found in the saliva of the Gila monster, has already been licensed to treat type 2 diabetes. Keen to test its effects in Parkinson's disease, Dr Thomas Foltynie worked with the drug's manufacturer and the Cure Parkinson's Trust to organise an innovative proof of concept trial, with positive results.
With safety data already available from earlier studies, a randomised controlled trial could in theory have been organised to test exenatide's efficacy in Parkinson's disease. However, such trials are expensive and there is inevitably a high risk of failure. Exenatide's makers were reluctant to commit to this step without gathering further evidence of its likely impact on disease.
Dr Foltynie and the Cure Parkinson's Trust, however, were keen to move things along faster. A major challenge to a large trial would have been the need to develop a placebo version of the pen-like device used to inject exenatide. Dr Foltynie therefore suggested running a single-blind randomised controlled - so patients would know whether or not they were taking the drug but assessors would not. The main drawback of this trial design is that any positive impact might simply reflect a placebo effect.
The trial of 45 patients lasted a year, and generated highly encouraging results. Not only did exenatide prevent the decline in motor and cognitive symptoms seen in control patients but performance actually improved, suggesting exenatide is not just neuroprotective but also has additional positive effects.
While placebo effects cannot be excluded with certainty, there are reasons to believe they were not a key factor. For example, improvement was gradual and sustained while a placebo effect would typically be more immediate and then decline.
Most importantly, quickly and at relatively low cost the trial has generated data suggesting that further studies of exenatide are warranted. Its manufacturers and the Michael J Fox Foundation are now supporting a larger placebo-controlled trial which Dr Foltynie will be leading. More generally, the trial illustrates how 'mini-trials' may act as cost-effective stepping stones in the development of promising therapeutics, enabling more agents to be tested in patients and reducing the risk of expensive failure at phase III.