New treatments for Parkinson disease are greatly needed, since current medications delay the progression of the disease but do not cure it. Most PD drugs focus on increasing levels of the dopamine that is lost due to degeneration of the substantia nigra. Unfortunately, often these treatments, such as L-dopa, simply trade one set of movement problems for another, since tardive dyskinesia eventually develops.
Preventative PD treatments are very appealing, particularly if existing already approved drugs are available. A group based in the United Kingdom may have found exactly this combination. The researchers, led by Ruth Brauer of the London School of Hygiene & Tropical Medicine, studied whether anti-diabetic glitazone (GTZ) drugs reduce the incidence of PD when compared to other anti-diabetes medications.
The group studied a primary care database of patient medical information from the United Kingdom Clinical Practice Research Datalink. They retrospectively analyzed data taken from people with diabetes who had been prescribed a GTZ compared to individuals with diabetes who took a different drug. They followed the patients’ medical records from 1999 to the time of their initial PD diagnosis, then up to either August 2013 (end of the study) or however long the patient remained in the database, matching all of the subjects in the two treatment groups by age, gender, and diabetes treatment stage.
The investigators were able to match 44,597 people who took GTZ to 120,373 people who took a different anti-diabetic medication. In their study report they noted that “175 GTZ-exposed individuals were diagnosed with PD compared to 517 individuals in the other antidiabetic drug-exposed group…PD in the GTZ-exposed group was 6.4 per 10,000 patient years compared to 8.8 per 10,000 patient years in those prescribed other antidiabetic treatments.”
People who had received GTZ had a significantly reduced risk of developing PD when compared to people who received a different drug for their diabetes.
GTZ medications act as agonists on peroxisome proliferation-activated receptor gamma (PPARÉ£). This receptor is found primarily in fat tissue, macrophages, and the colon. It aids in the regulation of fatty acid storage and the metabolism of glucose. But what might the role of PPARÉ£ have to do with preventing PD?
According to the authors, GTZ medications may have neuroprotective properties. They can block microglial inflammation by reducing the expression of matrix metalloproteinases that are released by dying neurons. GTZs might function to block a cascade of continuing cell death in PD. In addition, they noted that GTZ treatment “has been shown to increase brain mitochondrial biogenesis and the expression of antioxidant enzymes and antiapoptotic factors.” GTZ could therefore block programmed cell death in PD and may overall block the cycle of cell death and inflammation that occurs early on in the substantia nigra in people with PD.
Future trials may prospectively evaluate the use of GTZs in people with PD or even as preventive medications in those at risk for developing PD. In fact, a clinical trial is currently underway with the goal of examining whether pioglitazone can delay neuronal degeneration in early-stage PD in 216 participants, and details about this study can be found at Clinicaltrials.gov registration: NCT01280123. New medications, particularly preventative measures that can work at early stages of the disease, would be welcome additions to current treatments for PD.
• Anti-diabetic glitazone (GTZ) drugs reduce the incidence of PD when compared to other anti-diabetes medications.
• GTZ medications act as agonists on peroxisome proliferation-activated receptor gamma (PPARÉ£).
• GTZ medications may have neuroprotective properties and could act early on in PD to prevent disease progression.