Stem Cell Therapy for PD

This week Nature published data from two very important clinical trials. These trials revisit the potential for stem cell therapy to reverse the disease. The history of stem cell therapy in PD is rich, largely featuring the use of embryonic stem cells with some interpreting the data with enthusiasm and other skepticism. I'm not sure which perspective is right because those trials were small and the approach was not pursued to the point where anyone should claim to know the approached worded or did not.

These two studies used an amazing approach, each creating dopaminergic neurons in the laboratory that were then injected into the putamen, one of the brain regions that controls movement and which is the most markedly affected in Parkinson's. This approach creates dopaminergic neurons from other cells. In these studies one used embryonic stem cells and the other circulating blood cells as the starting point. The circulating blood cells are cultured in a way that makes them change their form to a cell very early in development, almost to the embryonic stage. Then each approach cultures the cells so that they differentiate into dopaminergic neurons. This can be done from a wide range of cells, even skin cells.

The goals of the studies was to demonstrate that delivering these stem cells into the brain is feasible as a clinical treatment, rather than to prove that stem cell therapy can reverse the disease. And the safety of this approach seems quite good. There were certainly adverse effects, though the publications report that the cell therapies were not responsible for any of these problems. And the problems do not reach the level of "serious" adverse effects, which is a very important and specific label to use in clinical trials, one that would be a major problem.

I'm a bit bothered by how some people report the results. The authors point out that conclusions about effectiveness are not proper in these trials that enrolled 12 or 7 patients, particularly when there is no placebo treatment for comparison. Nonetheless, it would be easy to look at some of the results and be excited. For example, when the Parkinson's experts evaluate how the participants are functioning, using Part III of the standard rating scale called MDS-UPDRS, the cell therapy appears to be beneficial. However, there is less attention to the results reported by the participants using Part II of the MDS-UPDRS, which does not show benefit. So the docs see improvement that the participants don't feel. That is not a win, though no one should expect a win in such a small trial.

Despite those data showing that we should not jump up and down with glee quite yet, I am very excited by these trial results. So many things could go wrong when you are injecting iPS cells into the brain. And they did not. So now we need to see the results of the next, larger trials, hopefully with randomization and proper control groups.

And let's use these trials as a reminder, just as we could use the results from the GLP-1 agonists. Even if the doctor sees improvement with a therapy, this is a disease where we need to see patients reporting they feel better, or similarly, that patients can perform a task better. When we get such results, that will be reason to celebrate.