Michael J. Fox Foundation, Gardner Center Put Spotlight on Landmark Biomarkers Study

People pose for photo

Mark Frasier, PhD, left, and Alberto Espay, MD. Photo by Cindy Starr / Mayfield Clinic.

A landmark study to find biomarkers for Parkinson’s disease was the subject of an animated discussion led by Mark Frasier, PhD, of The Michael J. Fox Foundation for Parkinson’s Research (MJFF)  and Alberto Espay, MD, of the James J. and Joan A. Gardner Family Center for Parkinson’s Disease and Movement Disorders last week at the Kingsgate Marriott. The meeting’s optimistic tone was underscored by Dr. Frasier, Vice President of Research Programs at MJFF, who said he believes that Parkinson’s biomarkers will indeed be found during the $45 million, five-year study.

“I’m optimistic that not one but several biomarkers will come out of this trial,” Dr. Frasier said.

The Gardner Center’s involvement in the biomarkers study – known as the Parkinson’s Progression Markers Initiative (PPMI) — was announced in early February, and Wednesday’s session allowed members of Cincinnati’s Parkinson’s community to learn more about the study and to ask questions. Dr. Espay, the Gardner Center’s Director of Clinical Research, is leading Cincinnati’s effort in the study. The Gardner Center is one of nine centers at the University of Cincinnati Gardner Neuroscience Institute, a component of UC Health.

Biomarkers are objective and reliable biological measurements of the underlying disease process, its progression, or of the response to therapy, Dr. Espay said. “Well known biomarkers for other diseases are blood pressure and cholesterol, for example. The absence of biomarkers for Parkinson’s disease creates room for diagnostic errors, precludes an assessment of how the disease may evolve or progress, and makes it difficult to measure whether any treatment is having an effect on the disease, rather than merely its symptoms. Precisely because of this gap, clinical trials need to include more people to account for the shortcomings in measuring disease progression and response to therapy.”

Therapeutic biomarkers can help “demonstrate whether a specific drug is actually hitting its intended target and having a biological effect,” Dr. Frasier said. This is similar to measuring cholesterol levels in the blood, which can help determine whether cholesterol-lowering drugs are having their intended effect.

PPMI is seeking both diagnosis and progression markers, which define the disease and change with the course of the disease, respectively. Objective, biologic biomarkers, once established, are tools that could be used to shorten the clinical testing portion of the drug development process by illuminating early on whether a drug is slowing or halting the relentless progression of Parkinson’s disease.

At present, no biomarker has been positively identified for Parkinson’s disease, meaning that doctors determine a therapy’s success by assessing their patients’ interpretations, which are necessarily subjective and, Dr. Espay said, “can vary from day to day and from person to person.”

PPMI is not MJFF’s first foray into the progression biomarker hunt. “One of my jobs is to manage the biomarker portfolio outside PPMI,” he said. “The Foundation has invested $30 million in this since 2002. There have actually been a number of hits and discoveries out of these projects. A ‘hit’ is an initial discovery in 20 to 30 individuals, and these hits have included a protein seen in cerebrospinal fluid (CSF) [which bathes the brain and spinal cord] and a blood biomarker in RNA.”

Because the studies were small, he continued, scientists must replicate them with a larger group to establish the validity of the findings.

The broad sweep and open availability of PPMI data, which is modeled after the Alzheimer’s Disease Neuroimaging Initiative (ADNI), will enable researchers to check these results and potentially discover more biomarkers. Over a period five years, researchers will examine brain scans and fluids – blood, urine and cerebrospinal fluid (CSF) – from two distinct groups. One group will consist of 400 individuals who have just been diagnosed with Parkinson’s disease and have not yet taken medication. The second group will be made up of 200 healthy individuals who do not have Parkinson’s disease in their immediate family and whose ages match up with the study participants who do have Parkinson’s..The initiative, which will expand to a total of 24 sites in 2012 , has been in process since 2010 and has enrolled more than 300 study participants.

The beauty of PPMI, Dr. Frasier said, is that by collecting a large swath of biologic material from a significant number of individuals, scientists will have the opportunity to replicate research that has pointed to biomarkers while also illuminating new biomarkers.

Signing up 600 participants is not as easy as it first appears. Study participants cannot have taken medication for their disease, and they may be asked to forego medication for several additional months. The study’s required CSF draw, via a spinal tap, is also a potential deterrent to some.

Dr. Espay, who was sporting an orange Fox Foundation-colored tie, told the audience that he himself does the spinal taps in a “patient-friendly” manner, with the study participant seated and leaning forward. An audience member who has Parkinson’s disease, and participated in a prior trial requiring a spinal tap, agreed, with a smile, that it was less uncomfortable than its reputation would suggest.

PPMI is a collaboration among the Fox Foundation, academic health centers, the National Institutes of Health and private industry. Data and collected samples will be open to all researchers seeking to perform biomarker verification studies. For more information about the study, please contact the Gardner Center at (866) 941-8264.

About the Parkinson’s Progression Markers Initiative
PPMI, a groundbreaking study to find biomarkers of Parkinson’s disease, is being carried out over five years at 24 clinical sites in the United States, Europe and Australia. The study will enroll 400 de novo Parkinson’s patients (patients who are newly diagnosed and have not yet taken PD medication) and 200 healthy age-matched controls. Participants will undergo tests including motor, neuropsychiatric and cognitive examinations; brain imaging with DatSCAN and MRI; and blood, CSF, urine and DNA sampling.

About the Michael J. Fox Foundation
The Michael J. Fox Foundation is dedicated to ensuring the development of better treatments, and ultimately a cure, for Parkinson’s disease through an aggressively funded research agenda. MJFF has funded over $285 million in research to date.

–Cindy Starr

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