2016 NETP Investigator Vignette

Title: Evaluating the Natural History of Prodromal PD in the PARS Cohort

Investigator: Kenneth Marek, MD; Institute for Neurodegenerative Disorders

Parkinson’s disease is a disorder which is diagnosed by clinical assessment, but very early in the disease it’s quite difficult to discern whether individuals might have Parkinson’s disease or some other disorder or simply just the growing old and getting slower in their ability to move about. And so, Parkinson’s disease diagnosis has been a dilemma for both the physicians who are trying to diagnose patients and for the patients and their families.

The PARS study is the Parkinson’s Associated Risk Syndrome study. It’s an effort to develop a cohort of individuals who are at-risk for Parkinson’s disease using a sequential biomarker strategy taking advantage of the early smell loss in Parkinson’s disease coupled with abnormal dopamine imaging to allow us to say these individuals are indeed at risk for Parkinson’s disease.

And that really is based on the premise that for Parkinson’s disease, as well as for other neurodegenerative disorders like Alzheimer’s disease or Huntington’s disease, there is a long period of time when there is degeneration in the brain but symptoms have not yet arisen. This preclinical or prodromal period really offers this enormous opportunity because we can potentially identify individuals at that stage who could then take advantage of clinical studies that might be used to test preventive medicines for Parkinson’s disease.

Years before the onset of the typical motor symptoms of Parkinson’s disease almost all Parkinson’s patients lose their sense of smell. So we have taken advantage of that early symptom in the PARS study to identify individuals who might have a loss of their sense of smell and coupled that with a novel technology, which allows us to image the dopamine pathology in the brain and coupling these two biomarkers to identify individuals who both have a loss of sense of smell and abnormal imaging who might be at risk to develop Parkinson’s disease.

The loss of smell that occurs in potential Parkinson’s patients, that is an easy thing to test, utilizing the University of Pennsylvania Smell Identification Test, or the UPSIT. The UPSIT is a set of four cards, which we sent by mail to over 10,000 people. These are simply scratch and sniff cards such as you would get if you looked in a magazine to smell perfume or-or some other odorant.

And they scratch and sniff and return them to us. We then identify them as having a loss of smell or a normal smell and we then ask a proportion of those individuals with normal smell and all of the individuals with abnormal smell to have additional much more rigorous testing including dopamine transporter imaging as well as examination and testing of their cognitive function, and other blood testing as well.

So in this type of study the proof is in the long-term pudding. So we now know that at four years, among those individuals who did have abnormal smell and abnormal imaging, about 60-percent of them went onto develop typical Parkinson’s disease. So we can see that this approach of identifying individuals prior to the onset of symptoms was successful in identifying a group of individuals who ultimately developed Parkinson’s disease.

The DoD programs have been essential for our research programs. And it really took great foresight from the DoD programs because this really required identification of a novel idea and had the follow-through to enable us to continue to follow these individuals for now again up to eight years which is really remarkable in a research project.

What we would like to do is now begin to couple the identification of subjects in this way with testing of newer drugs, which might actually slow down the progression of disease and ultimately the goal is to utilize those drugs even prior to the onset of symptoms to prevent the illness. That’s not where we are now, but we are getting closer to that goal.