If you’ve read the technical-language post below and are intrigued but confused, here’s a plain English version. Use the Comments section below to tell me if it’s clear enough for an educated non-technical reader.
The current issue of the journal Movement Disorders includes two articles on a recent trial of an experimental drug for PSP. The journal’s editors asked me to write an “editorial” (actually, an overview for the sake of perspective) for the journal’s technical readers. That appears in the same issue and its main point is this:
The two original papers in Movement Disorders report a trial of the experimental drug “tideglusib” in 146 people with PSP. (The drug is not approved in any country or available in pharmacies.) The study took place in 2011 and 2012 at multiple institutions in the US, Spain, Great Britain and Germany. Like any good trial, it included administration of a dummy treatment (a “placebo”) to some of the people with PSP randomly chosen as a comparison group. The neurologists doing the study tested all of the subjects with the PSP Rating Scale, which is the standard test used in research on PSP, at the start and end of the one year of treatment. No one expected tideglusib to give improvement over time; the best outcome hoped for was that the rate of decline would be slower on tideglusib than on placebo.
As a kind of supplementary part of the study, 37 of the 146 patients also received a brain MRI at the start and end of the year of treatment in addition to the PSP Rating Scale. The idea was to compare the patients on tideglusib with those on placebo with regard to the amount of shrinkage (“atrophy”) of various parts of the brain over the year of the study. This was added mostly as a test of the ability of MRI to provide an objective test to supplement the PSP Rating Scale, which uses interview questions and physical examination.
The overall study, unfortunately, showed absolutely no benefit of tideglusib over placebo on the PSP Rating Scale. But the sub-study using MRI did show quite a difference, 58% less atrophy of the cerebrum on tideglusib relative to placebo.
Now, some researchers have known about this result for several months because they heard its principal author, Dr. Günter Höglinger of Munich, Germany, present it at conferences. Most experts whom I have spoken to find it hard to accept that the MRI could show an effect of the drug without any effect on the PSP Rating Scale or on any of the other physical or psychological examination measures that were applied.
Some of the skeptics point out that the group of 37 receiving the MRI may have been too small to be representative of the overall group of 146 and that the 9 patients on placebo may have been different from the 28 patients on tideglusib even before the study began. It’s true that these numbers of patients are awfully small for drawing definitive conclusions and raise the possibility of a statistical fluke.
Others object on grounds that the most pronounced effect on the MRI was in the areas of the brain least affected in PSP. But since I’m a “glass-half-full” kind of guy, I see this as a clue to guide further research. Maybe brain tissue in the more advanced stages of PSP is beyond help of this particular drug, and only the more PSP-resistant, slowly-degenerating parts of the brain responded. If so, maybe that means that we should look for ways to improve tideglusib rather than discarding it because it gave no outwardly measurable improvement. Another conclusion is that we should work on ways to diagnose PSP earlier, when no part of the brain has progressed beyond the ability of a drug like tideglusib to help.
In another post, I’ll explain what tideglusib does in brain cells. It’s complicated.