Ambroxol?

This week's JAMA Neurology published an eagerly awaited study testing the utility of ambroxol - a medicine developed to treat coughing - to reverse cognitive dysfunction. This was an ambitious and important trial that evaluated memory, speech, executive function, etc. using a wide range of tests. It also looked at motor function with a direct measurement (the timed up and go test) and used the UPDRS instrument to assess overall clinical status.

It was a small study that randomized 55 people to drug or placebo, but that is a big effort when performed at a single center as this one was.

The reasons so many people are excited about ambroxol include: (1) it could improve lysosomal function which is a key abnormality in the brain cells of people with Parkinson's and (2) as a repurposed drug we already are confident that it is safe. In fact, it is so safe that some doctors use it in women who are pregnant.

These investigators conducted this complex trial to determine whether the drug prevented loss of cognitive function over the course of a year. They concluded that "ambroxol was safe and well tolerated..." but that "there was no significant effect of ambroxol on cognition after 52 weeks..." and "...there were no statistical differences between groups on secondary outcome measures." And this study included a large number of secondary endpoints. While the study is not large enough to tell us that there is no way the drug could work, the lack of benefit in any of the many secondary assessments speaks against any optimism about this drug for PD.

And while the study did not show an increased risk of serious adverse events, there were more patients who withdrew therapy who were receiving ambroxol than for those receiving placebo for problems that were neuropsychiatric. And more people withdrew due to an adverse event in the ambroxol treated group than in the placebo group (26% vs. 12.5%). The drug was also associated with more hospitalizations for an adverse event than were associated with placebo therapy (20% vs 12.5%).

There are several studies completed and ongoing with ambroxol. Perhaps they will show that the drug works in people with the GBA1 gene variant. We'll learn - but for now, the drug does not seem to have a place in therapy for Parkinson's disease, even in countries where the drug is available, due to lack of benefit and reason to be concerned about risk of hospitalizations for adverse events.