Spinal Shocks Alleviate Parkinson's Symptoms in Pre-clinical Models: What Does It Mean for People with PD?
In March 2009, researchers at Duke University reported in the journal Science that by electrically stimulating the spinal cords of rodents, they had reversed some of the worst symptoms of Parkinson's disease. The Michael J. Fox Foundation spoke to Erwan Bezard, PhD, of the University of Bordeaux (France) about the potential of the work to lead to a novel treatment for people with Parkinson's disease. Dr. Bezard, who sits on MJFF's Executive Scientific Advisory Board, is a leading expert in the brain areas affected by Parkinson's disease and in assessing experimental interventions in pre-clinical models of the disease.
MJFF: How significant is this finding? Would you say that it is field-changing?
EB: It is too early to say that it is field-changing. In science, you need a bunch of papers replicating any given finding before you say that. With that said, it is extremely interesting and intriguing. I anticipate that many labs will now start working on spinal stimulation approaches, both to replicate the data on the improvement in symptoms, as well as to see whether the results are similar in other pre-clinical models of PD.
MJFF: What exactly did the researchers do?
EB: They basically stimulated the spinal cords of rodent models of PD with an electrode that covered, but was not inserted into, the spinal cord. They then saw movement restored in these models.
The work was done in the dorsal column of the spinal cord, so the researchers are calling this intervention "dorsal column stimulation," or DCS.
MJFF: Were the rodents able to walk only during the actual stimulation?
EB: Yes. The movement effect was only really during and shortly after the period of stimulation.
MJFF: So, it seems that to get the beneficial effect of DCS in humans, you would need to keep stimulating their spinal cords continuously. Is this safe?
EB: It is uncertain whether the effect could be prolonged for a time, as well as whether a more prolonged stimulation would be harmful to the spinal cord. To the latter question: Based on what we've seen with deep brain stimulation (DBS -- a brain surgery in which electrodes are implanted to stimulate an area of the brain affected in PD) in the past, I don't think there would be a lesion induced on the spinal cord, but there might be a potential side effect caused by the stimulation itself. When you stimulate the spinal cord, the overall effect highly depends on the intensity of the stimulation, which is quite high here.
Everything could be modified in future experiments, of course, and I guess that will be done by this team and also by other teams, which will soon undertake experiments to investigate this.
MJFF: What else does DCS have in common with DBS? Is it similar, or is it different because it's in the spinal cord instead of the brain?
EB: The rationale is very much the same. In DBS you have electrical stimulation of a deep brain structure to disrupt "pathological" oscillations of the subthalamic nucleus. Both methods appear to work through a similar mechanism -- correcting abnormal electrical activity that gives rise to the symptoms of PD. This project used a very high frequency -- about 300 Hertz. By comparison, the frequency used in DBS is usually about 130 Hertz.
But in terms of performing the surgery, if this works, it will be dramatically different from DBS. It is much less invasive, because you don't need to go into the brain. The risk of infection, the risk of every kind of problem or complication is much lower. This is good news -- you would expect to see a much greater penetrance than DBS has achieved, and many more patients would benefit. There are a great deal of patients who would benefit from DBS but understandably choose not to undergo it because of the risks associated with brain surgery under any circumstances.
MJFF: What about unpleasant side effects from long-term stimulation of the spinal cord?
EB: There are side effects. One is a feeling of constantly being on pins and needles. Assuming this moves forward as a therapy, there would be a choice for patients between living with the effects of the disease, and living with the side effects of this treatment. Only patients can truly say whether this treatment is, on balance, tolerable. That will happen when and if this work moves forward to the clinic.
MJFF: According to the news reporting on this story, the original team is now working to replicate the results in non-human primate models of PD, and the lead investigator said that if it works there, we could see clinical trials within a few years. Do you agree with this assessment?
EB: Absolutely, he's right! If you look back to DBS, it was three months after the demonstration of success in non-human primates that the procedure was first performed in humans.
MJFF: What is the timeframe for next steps on DCS?
EB: We have to be cautious, and for the time being, it would be advisable not to get our hopes up too high. This is an important paper. But one paper does not make a discovery. One paper could be a discovery, if 10 or 15 others are able to confirm and refine it. But it becomes a discovery only well after the publication. So we need to wait to be sure that this is a discovery and not just an interesting observation. Three years ago there was an exciting paper about motor cortex stimulation for PD. But the clinical investigations failed to replicate the preclinical finding.
In this case, there is a great deal more work to do for this work to be completely convincing. It needs to be tested in other models. That the researchers are now going into non-human primates is very good news. Certainly we are all looking forward to seeing the results from that work.
NOTE: The medical information contained in this article is for general information purposes only. The Michael J. Fox Foundation has a policy of refraining from advocating, endorsing or promoting any drug therapy, course of treatment, or specific company or institution. It is crucial that care and treatment decisions related to Parkinson's disease and any other medical condition be made in consultation with a physician or other qualified medical professional.