For Parkinson’s patients, medication can be a double-edged sword: It can beat back the symptoms of the disease, allowing a patient to move or talk more freely, but it can also cause severe vomiting, dizziness, and low blood pressure to the point of passing out.
Now, as reported in the Journal of Physiology on Tuesday, researchers in Italy may have found a way to harness the benefits of Parkinson’s drugs while reducing their side effects.
It didn’t require modifying the drugs. Instead, the therapeutic trick involved training a patient’s neurons as if they were lab rats or dogs hoping for a treat.
Give a dog a bone every time you come into the room, and it will start salivating as soon as you cross the threshold. The same may be true of a neuron, it turns out.
If it gets the neurotransmitter equivalent of a cup of coffee every time, an injection to the body, it will start perking up even if the syringe contains nothing but saline solution.
“Neurons can learn to respond to placebos,” said study author Elisa Frisaldi, a neuroscientist at the University of Turin Medical School. “This is the first step in order to improve the clinical protocols, with the final aim to reduce the drug intake and the side effects, which is a big problem for Parkinson’s disease.”
In Parkinson’s disease, neurons responsible for producing dopamine begin to degenerate and die, leading to involuntary tremors, cognitive impairment, and eventually dementia. Some Parkinson’s drugs can temporarily stimulate a burst of dopamine in a patient’s brain, restarting the circuit that gets people moving normally. Frisaldi’s team wanted to see how they could create the same effect with a placebo.
They recruited 42 patients who were about to undergo a treatment called deep-brain stimulation, in which a surgeon sticks an electrode into the patient’s brain, delivering an electrical impulse that can help set movement back on track. Because these patients were already going to have electrodes in their brain, the researchers could ethically insert a few others, to measure the activity of specific neurons.
The researchers divided these participants into six groups. They all got deep-brain stimulation, but some got an extra boost: either one, two, three, or four daily injections of a dopamine-stimulating drug called apomorphine before their surgery. Then, during their surgery, some were given a placebo injection, while the researchers measured their neuronal activity with electrodes, and had a neurologist evaluate the stiffness of the patient’s joints.
They found that the number of dopamine-stimulating injections had an effect on how well the placebo worked. The more times a real drug had been delivered beforehand, the less stiff the patient’s joints became and the more those dopamine-activated neurons fired at the time of the saline injection. Without the real injections in the days leading up to the surgery, the placebo had no effect.
“It is remarkable to think that — while there is a great deal of effort in trying to develop more refined and disease-specific oral and surgical therapies for Parkinson’s — that all along we have had a source of improvement that requires no industrial production, no pharmaceutical companies, no clinical trials,” said Dr. Alberto Espay, a neurologist at the University of Cincinnati College of Medicine, who was not involved in the study.
“Patients themselves [are] harnessing that power, within them, of expectation.”