Friday March 20 2009
The stimulation electrode (red) is implanted above the spinal cord. Picture courtesy of the AAAS
“An implant that stimulates nerves in the spinal cord could ease the suffering of Parkinson's disease sufferers,” the Daily Mail reported. The newspaper said that in experiments in mice, immobile mice became active and “seemingly healthy” within seconds of the device being switched on. The Daily Mail said that the technique is much less invasive than current nerve stimulation devices for easing symptoms of Parkinson's disease.
The mouse study behind these reports is early research, but the findings are promising. Whether they can be applied to human disease will be clearer if the work progresses to primate models of Parkinson’s disease, and then into human studies. Further study of the technique – called dorsal cord stimulation – is recommended by the researchers. Given that other existing treatments for Parkinson’s are not effective in the long-term and have side effects, this is an important direction for research.
Where did the story come from?
The research was carried out by Dr Romulo Fuentes and colleagues from the Duke University Medical Center in Durham, Lund University in Sweden, the Edmond and Lily Safra International Institute of Neuroscience of Natal in Brazil, and the Ecole Polytechnique Federale de Lausanne in Switzerland. The study was funded by the National Institute of Neurological Disorders and Stroke, and the International Neuroscience Network Foundation. It was published in the peer-reviewed medical journal Science.
What kind of scientific study was this?
Parkinson’s disease is a chronic neurological condition that affects the way the brain coordinates body movements, including walking, talking and writing. Parkinson's disease affects each individual differently, and each person with the condition will have a varied collection of symptoms and respond differently to treatment. The severity of symptoms also varies between individuals with the condition. These symptoms typically include slowness of movement and poor coordination (known as bradykinesia), a resting tremor (often in the hands), stiffness or rigidity in the limbs, as well as other problems, including slow speech, an inexpressive face and altered mood.
Parkinson’s disease is caused by a loss of the nerve cells in the brain that produce dopamine. Dopamine helps to transmit messages from the brain, which control and coordinate body movements. It is not yet known what causes this nerve damage.
In its early phases, Parkinson’s disease can be treated with dopamine replacement (levodopa), but this is less effective in the long term, and it has side effects, e.g. some people develop involuntary movements (called dyskinesia). There is a surgical procedure called deep brain stimulation, which could help improve the movement disorders of Parkinson’s. However, it has side effects, and the surgery is invasive and involves implanting electrodes deep into the brain to stimulate specific parts. As such, there is ongoing research into less invasive ways of managing symptoms.
In this study, the researchers explored the effects of a low-frequency current on the nerves that run along the spine (dorsal column stimulation, or DCS) in mice with a disease similar to Parkinson’s. The researchers used medication to stop dopamine production in normal mice and in mutant mice that were already unable to transport dopamine efficiently. These mice had symptoms that were similar to those seen in Parkinson’s patients, namely reduced movement and altered brain activity.
The DCS was delivered as an electric current through platinum electrodes to nerves in the mouse spine. The researchers looked at the effects of DCS both before and after the mice were depleted of dopamine. The researchers also explored what effect dopamine depletion and DCS had on the mice neurons, and carried out further experiments to determine the minimum level of levodopa treatment in combination with DCS needed to restore movement to dopamine-depleted mice. This was done by gradually increasing (through hourly injections) the dose of levodopa in dopamine-depleted mice, and observing the effects on their movement.
Effects of DCS were also examined in another mouse model of Parkinson’s. In this model, mice were depleted of dopamine and damage was induced in the striatum part of their brains. This acted as a better mirror of the damage seen in the nigrostriatal pathway (nerves connecting the substantia nigra and the striatum) in Parkinson’s patients. The mice were observed for an hour without DCS, after which they were given DCS for 30 seconds every 10 minutes for an hour. Patterns of movement seen in the second hour were compared to the first.
What were the results of the study?
The researchers found that DCS improved movement in mice that were depleted of dopamine. When given the highest frequency (300Hz) of stimulation, mice had on average 26 times more movement than they had in the five minutes prior to stimulation. There was also some increase in movement following stimulation in mice that were not depleted of dopamine (average movement increased by about five times). Slow movements (bradykinesia) were also reduced. All improvements usually began a few seconds after stimulation started.
When DCS stimulation was used alongside levodopa, a fifth of the dose of levodopa was needed to restore the same amount of movement than with the drug alone.
In animals with more chronic brain lesions, DCS increased movement during stimulation, and continued to do so for about 100 seconds after stimulation.
What interpretations did the researchers draw from these results?
The researchers conclude that their study used a semi-invasive method to restore movement capability in two different Parkinson’s disease models in mice. The researchers conclude that DCS plus levodopa is superior to levodopa alone in improving locomotive activity. They put forward some theories about the effect of the treatments on the brain.
What does the NHS Knowledge Service make of this study?
This study in mice has opened up an important avenue for further research into semi-invasive treatments. These could potentially complement existing treatments for early-stage Parkinson’s.
The researchers propose that DCS should be investigated in "primate models of Parkinson’s". Such studies would more closely resemble how the treatment might work in humans. At present, there is no cure for Parkinson’s disease. Existing treatments help control symptoms, but these have limited effectiveness and they have many side effects. This is an important direction for research.