Is deep brain stimulation neuroprotective if applied early in the course of Parkinson’s Disease?


This is an important question. until now all medication for Parkinson’s disease relieved the symptoms of this disease for a while. The medication couldn’t prevent the progression of the disease resulting in lack of efficacy of the medication. Increasing the dosage until side-effects or adding another therapeutic temporarily resolved the symptoms until the progression again decreased their efficacy.

Hundreds of putative neuroprotective agents have been tested in clinical trials over the past two decades, but none of these agents has been successful at preventing the progression of PD.

In a recent Viewpoint in Nature Clinical Practice Neurology the authors claim that:

We believe that DBS will be the first therapy proven to slow PD progression, and that it must be applied in the earliest stages of the disease to have such an effect.

They base their opinion on the results of animal research. From these animal models it was learned that high frequency deep brain stimulation can be neuroprotective. The animals received DBS during ongoing neurodegeneration, which more accurately represents clinical practice and DBS at high frequency has inhibitory effects on this neurodegeneration.

Results from clinical trials are contradictory. In some trials no significant clinical deterioration during 4 years of DBS therapy could be found, while many trials have noted clinically and statistically significant deterioration of motor symptoms after initiation of DBS therapy.

The authors have stron arguments for these conflicting results:

First, continued functional decline does not eliminate the possibility of positive disease modification—it only eliminates the possibility that DBS might result in a complete halt in progression. Furthermore, none of the studies so far has included a control group that was treated with standard drug therapy, and, thus, progression rates between the two groups have not been compared.

An additional limitation is that all studies to date have been in patients with features of advanced PD, including motor complications of therapy. Currently, patients do not receive DBS therapy until they have developed intractable symptoms and motor complications of therapy; electrode implantation both in clinical trials and in standard of care takes place at an average of 11 years after diagnosis, at which point considerable cell death has occurred, and potentially neuroprotective strategies are unlikely to demonstrate a clear benefit.

The authors have started a pilot clinical trial ( identifier NCT00282152) to study the neuroprotective effects of DBS in Parkinson’s Disease. They will test the hypothesis that DBS slows the progression of early stage PD.

You can read some more about this trial on Viewpoint in Nature Clinical Practice Neurology.

Hope they will succeed in confirming their hypothesis for such a debilitating disease.
Charles, P., Gill, C., Davis, T., Konrad, P., & Benabid, A. (2008). Is deep brain stimulation neuroprotective if applied early in the course of PD? Nature Clinical Practice Neurology, 4 (8), 424-426 DOI: 10.1038/ncpneuro0848