A class of diabetes drug that limits insulin resistance may also work to reduce the risk of Parkinson’s disease, researchers have found.
Parkinson’s disease is a common, progressive neurological disease caused by the gradual loss of nerve cells that normally produce dopamine, a neurotransmitter that regulates the body’s movements.
It usually develops from around 60 years of age. Symptoms develop slowly, and can include trembling of the hands, legs, arm, jaw, and face, slow movement, and muscle stiffness. There is currently no way to halt the loss of dopamine-producing nerve cells, but medications that replace or mimic the lost dopamine can reduce the severity of symptoms.
This study focused on thiazolidinedione drugs, which are widely prescribed for diabetes. Previous findings indicated that the drugs may have properties that help protect neurons in the brain. The drugs work by activating a receptor found inside cells in many different body organs called the “peroxisome proliferation-activated receptor gamma (PPARɣ) receptor.” This benefits diabetics, as the thiazolidinedione drugs reduce insulin resistance. But the receptor affects several other bodily processes, too.
A team at the London School of Hygiene & Tropical Medicine, UK, looked at the impact on Parkinson’s risk in humans. Dr. Ian Douglas and colleagues took figures from the UK Clinical Practice Research Datalink on more than 160,000 diabetes patients.
Those who were prescribed thiazolidinediones (either rosiglitazone or pioglitazone) were compared with other patients similar in age, sex, location, and diabetes treatment stage who were given different antidiabetic drugs. The study was funded by The Michael J. Fox Foundation for Parkinson’s Research.
The rate of Parkinson’s disease was 6.4 per 10,000 patient years in the thiazolidinedione-exposed group, and 8.8 per 10,000 patient years in those who took different drugs. This equates to a 28 percent reduced rate, which was still seen when smoking, other medications, head injury, and disease severity were taken into account.
But when the researchers looked at past and current thiazolidinedione users separately, they found that the risk of Parkinson’s was only seen in patients currently using a thiazolidinedione (who had a 41 percent decrease in Parkinson’s), not those who had previously used thiazolidinediones but stopped or switched to another medication.
“The risk was reduced in those with current thiazolidinedione prescriptions but not reduced among those with past prescriptions,” the team reports in the journal PLoS Medicine. This indicates that there is “little to no persisting benefit of previous thiazolidinedione use.”
In conclusion, they state, “PPAR gamma pathways may be a fruitful drug target in Parkinson’s disease.”
Dr. Douglas points out that this is the first study to show the relationship between thiazolidinedione use and the rate of Parkinson’s disease in humans.
He says, “We often hear about negative side effects associated with medications, but sometimes there can also be unintended beneficial effects. Our findings provide unique evidence that we hope will drive further investigation into potential drug treatments for Parkinson’s disease. It’s thought that around one in 500 people are affected by Parkinson’s, and to date no effective treatments have been found to directly tackle the neurodegenerative aspect of the disease.”
Co-author Dr. Ruth Brauer added, “Our results suggest that treatments which activate the PPARɣ receptor in the same way as thiazolidinediones could be promising targets in future drug research. Although our study only looked at people with diabetes, we believe it’s likely that the protective effect of thiazolidinedione may also be seen in people without diabetes.”
This study did not look at whether taking these drugs slows or prevents the progression of the disease once it has begun. However, another recent study suggested that one drug in this class, pioglitazone, is unlikely to modify progression in early Parkinson’s disease, at least at the doses studied. Investigators from the National Institute of Neurological Disorders and Stroke assessed the effect of pioglitazone on the progression of Parkinson’s disease.
In their trial, 210 individuals with early Parkinson’s disease were assigned to 15 mg/day pioglitazone, 45 mg/day pioglitazone, or placebo. After 44 weeks, the patients’ Parkinson’s disease severity was measured. Compared with their severity at the start, those taking pioglitazone at both doses were similar to those on placebo.
“These findings suggest that pioglitazone at the doses studied here is unlikely to modify progression in early Parkinson’s disease,” writes the team in The Lancet Neurology. “Further study of pioglitazone in a larger trial in patients with Parkinson’s disease is not recommended.”
They add that this class of drugs also bring some serious negative side effects. Pioglitazone has been linked to bladder cancer, and the thiazolidinedione drug rosiglitazone was in fact suspended from the market due to safety concerns over risks to the heart. Later, the FDA removed these restrictions.
Brauer, R. et al. Glitazone treatment and incidence of Parkinson’s disease among people with diabetes: a retrospective cohort study. PLoS Medicine, 21 July 2015 doi: 10.1371/journal.pmed.1001854
NINDS Exploratory Trials in Parkinson Disease (NET-PD) FS-ZONE Investigators. Pioglitazone in early Parkinson’s disease: a phase 2, multicentre, double-blind, randomised trial. The Lancet Neurology, 23 June 2015 doi: org/10.1016/S1474-4422(15)00144-1