There's a new report of progress in Parkinson's disease, and from an unexpected direction. Well, it was unexpected for me, anyway. Parkinson's is, famously, a condition that is driven by the steady deterioration of dopamine-rich neurons in the brain, most particularly in the substantia nigra region. An impressive amount of research over the years has gone into the study of this part of the brain and to dopamine handling in general. What sets off Parkinson's and how to interrupt its progress are still very much open questions. It's almost certainly a combination of genetic and environmental causes, but the details of that tangle are yet to be made clear.
This latest work, though, involves dosing a known diabetes medication, the GLP-1 agonist exenatide. That's a peptide drug, famous among those who follow these things (I'm one) as having been derived from an active protein found in Gila monster saliva. Type II diabetes does seem to be a risk factor for Parkinson's (as well as for Alzheimer's), and there's been a lot of work on the "gut-brain axis" and what's connected to what. Exenatide has effects on appetite, crosses the blood-brain barrier to some degree, and has shown protective and growth-factor effects on neurons in vitro. So it's certainly possible that it could have neuroprotective effects on a degenerative disorder like Parkinson's, and this paper is the first double-blinded trial putting that idea to the test.
There's some promise. This was not a large trial (about thirty patients in each group), but at 60 weeks (48 treatment and 12 weeks of washout) motor function did seem to improve slightly in the treatment group, while it continued to worsen in the controls. The same team had previously done an open-label proof of concept study, and that one showed motor improvement as well, along with an even more significant change in cognitive assessment scores. This one, though, showed no real change in the latter, which tells you something about open-label measures of cognition and mood. But based on the motor function data, this could lead to a completely new direction in Parkinson's therapy.
It needs one. There's not a lot that can be done for Parkinson's patients, outside of dopamine replacement, which isn't that effective in the long run. This study is encouraging, in that it shows that there could be a route to neuroprotection outside of what's been tried already. But at the same time, it's worth thinking about this recent item, on statistics in biomedical and social science data. There's been a call to reduce the threshold for what's considered significant from the traditional p=0.05 down to p=0.005. If that's the threshold, then this paper's results don't make the cut: they have p=0.03. So when if I say that the data do seem to be real, keep in mind that that's for certain values of "real". There's a limit to what you can get in a trial this small, of course (which takes us back to the concept of effect size). And that means that the first thing to do, when you get a result like this, is to see if it holds up in a larger population.
"Run it on a larger population" is the general answer for statistical doubts (and in fact has been proposed as an alternative to that p-lowering proposal), but that means that a lot of studies just wouldn't be done in the first place for lack of funding. Some of them won't be missed, but some of them surely will be, so it's a cost/benefit analysis and a difficult one to get a handle on. So is the p=0.005 proposal, of course: that will mean more negative studies, some of which will be even-harder-to-overcome false negatives, and all of them will be harder to publish under the current editorial systems. Nothing gets improved for free.
Do I think that the benefits seen in this Parkinson's study are real? Yeah, if pressed, I think so - probably. The overall mechanism makes sense, and there are several lines of evidence that point the same way from earlier work. But at the same time, I wouldn't go wild until seeing it reproduced in a larger cohort of patients, which will take a lot more money and time (and remember, this is already the larger cohort as compared to the first preliminary trial). There were no particular adverse event flags in this study, but in the same way that you have to be cautious about the good parts, you have to be cautious about the bad parts, too. So anyone with Parkinson's who's thinking about trying this therapy free-lance should keep that in mind as well; it's yet another trade-off.
This is why we run trials. And this is why the trials have to be big ones, and long ones, and expensive ones. I very much hope that this points the way to a new Parkinson's therapy, but it's honestly still too soon to say that it's there yet. Things have to hold up, and we have to find out if they do.