Friday August 4 2017

There are an estimated 127,000 people in the UK with Parkinson’s disease

Exenatide may have neuroprotective effects

“A drug commonly used to treat diabetes could help those living with Parkinson’s disease,” The Guardian reports. A small study suggests a drug called exenatide may have a modest beneficial effect on motor (movement) symptoms in people with Parkinson’s disease.

Exenatide is known as a GLP-1 agonist, used to help regulate blood sugar levels in people with diabetes. Previous, early-stage research also suggests it may help protect nerves against damage, which is the root cause of Parkinson’s.

The study looked at changes to people’s movement (“motor”) ability when given either an injection of exenatide or a placebo injection. The people in the study had their motor ability assessed by a well-validated scoring tool before taking the drug, at various points during the trial, and 12 weeks after they were last treated.

At the final measuring point, people who had received exenatide had shown a small improvement in their motor scores, while people in the placebo group had got worse. However, the difference between those changes was modest. People receiving exenatide did not report any significant improvement in quality of life.

Nonetheless, it is an interesting finding warranting further research into the longer-term effects of giving exenatide to people with Parkinson’s disease.

It could be the case that a repurposed GLP-1 agonist specifically designed to treat Parkinson’s would provide more benefit.

Where did the story come from?

The study was carried out by researchers from University College London, the Leonard Wolfson Experimental Neuroscience Centre in London and the National Institute of Aging in Baltimore. It was funded by The Michael J Fox Foundation for Parkinson’s Research and the Department of Health National Institute for Health Research Biomedical Research Centres.

The study was published in the peer-reviewed medical journal The Lancet.

Overall the UK media covered the research well, though the headlines tended to overstate the impact of the drug on symptoms and the significance of these very early findings.

The Mail Online’s assertion that the drug could “halt” Parkinson’s was particularly optimistic as the results only indicated a slight change in motor symptoms and no change in any other symptoms.

BBC News’ headline “First hints Parkinson’s can be stopped” is a more realistic appraisal of the research.

What kind of research was this?

This study was a randomised controlled trial (RCT) comparing people given the diabetes drug exenatide with those who were given a placebo. During the study, neither the people who were in the trial nor their doctors knew which drug they had received, so the RCT was double-blinded – the best way of assessing an intervention. Although the study was quite small, the researchers were still able to find some differences between the two groups of people at the end.

The main aim of the study was to see whether exenatide had a beneficial effect on people’s motor scores 12 weeks after completing the 48-week course of drugs.

What did the research involve?

The researchers recruited 62 people to the study and randomised them to receive either exenatide (32 people) or a placebo drug (30 people). Both drugs were given to people in the form of injections, which they used themselves. People took the injections for 48 weeks while carrying on their normal medication, and then stopped the injections while continuing to be studied for an additional 12 weeks.

People were eligible to take part in the study if they:

  • were aged 25-75 years
  • had idiopathic Parkinson’s disease (where the cause is unknown)
  • were taking “dopamine boosting” (dopaminergic) drugs such as Levodopa, where the effects start to wear off before the next dose is taken
  • were considered able to self-inject the drug
  • were at Hoehn and Yahr stage 2.5 or less during treatment (the Hoehn and Yahr scale is a five point scale used to describe the severity of symptoms, so participants were no more than halfway through disease progression)

People who had dementia, diabetes, or a body mass index (BMI) below 18.5 were not allowed to join the study.

The researchers took various measurements of people before, during and after the study, including the Movement Disorders Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS); which consists of five different sections, or parts, assessing different sets of symptoms.

The main measure they looked at was the MDS-UPDRS 3 score, which measures motor ability on a scale of zero (no symptoms) to 132 (very severe). They were particularly interested in how people scored after the 12-week period of no injections at the end of the study. Each assessment was performed first thing in the morning before they had taken their usual dopaminergic medication and then one hour after taking their dopaminergic medication.

The data was analysed on the basis of what drug people were supposed to have taken, regardless of whether they continued on that treatment for the whole of the study. This is an appropriate way of analysing this kind of data.

What were the basic results?

At 60 weeks, before taking their daily dopaminergic medication:

  • In the group receiving exenatide, people had an average improvement in MDS-UPDRS 3 shown by a reduction from 32.8 to 31.9 (change 1.0, 95% confidence interval [CI] 2.6 to 0.7).
  • Motor scores of the people in the placebo group had on average worsened, from 27.1 to 29.2 (change 2.1, 95% CI 0.6 to 4.8).
  • There was an average difference between the two groups of 3.5 (95% CI 6.7 to 0.3), meaning that people in the placebo group overall had worse motor scores than those receiving exenatide.
  • There were no statistically significant results in any other part of the MDS-UPDRS score such as MDS-UPDRS 1 which assesses mood, or MDS-UPDRS 2 which looks at how badly daily activities of life have been affected.

After taking their daily dopaminergic drugs:

  • The scores on the MDS-UPDRS 3 improved in the exenatide group to 19.9 and in the placebo group to 14.5.
  • There were no differences between the two groups on any other part of the MDS-UPDRS either at 48 or 60 weeks.

How did the researchers interpret the results?

The researchers highlighted the benefit on motor scores of taking exenatide, but acknowledged that there was no difference in scores between the two groups in the other parts of the MDS-UPDRS while taking the drug. They also noted no difference was observed between the two groups of people when looking at their mood, cognition, non-motor symptoms, dyskinesia (involuntary movements like tremors) and quality of life.
 
The researchers also noted some small differences at the beginning of the study between the two groups. People in the exenatide group were slightly older, had higher baseline MDS-UPDRS 3 scores, and had lower Levodopa equivalent doses than people in the placebo group.

While RCTs try to match different groups as much as possible, this can be harder in trials with smaller populations, such as this one.

Conclusion

This research shows some interesting early findings, though the magnitude of effect was very small compared to the improvements in symptoms with current dopaminergic drugs. The study was well conducted but did have some limitations:

  • The number of people taking part was quite small. This may have meant it was hard to detect any other benefits or harms of taking the drug other than the effects on motor scores.
  • The period of time people were given the drug and followed up meant that longer-term effects could not be measured.
  • The benefit of the drug observed so far might not be big enough to make a difference to people’s day-to-day lives, but this may change with a longer or larger study.

Overall, this well-designed piece of research indicates that it would be worth carrying out further studies of longer-term outcomes in bigger populations.

It could well be the case that a repurposed version of exenatide, or similar GLP-1 agonist, could prove more successful.