Evaluating the Natural History of Prodromal PD in the PARS Cohort
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.