Projects Will Search for Parkinson's Biomarkers
Funding for the $40 million PPMI study will come from the Michael J. Fox Foundation, private contributions, Pfizer Inc., and – Dr. Marek hopes – federal grants.
In fact, he said, PPMI leaders hope to become involved in the PD-BIN.
Although the request for applications for the PD-BIN was just released (https://grants.nih.gov/grants/guide/rfa-files/RFA-NS-11-005.html
“The deputy director of NINDS [Dr. Walter J. Koroshetz] made it clear that the goal of this project is to bring as many resources as possible to bear on advancing neuroprotective therapy for Parkinson's,” Dr. Hallett said in an interview.
Although not officially connected, the PD-BIN and the PPMI may join forces, Dr. Marek said.
“We'll be applying for [the federal project] and we would love for these processes to be complementary. We would be delighted to have the government, through NIH, partner with us.”
Both projects were largely inspired by the Alzheimer's Disease Neuroimaging Initiative (ADNI), a public-private collaboration launched in 2004. ADNI discoveries have shown that cerebrospinal fluid carries disease-specific biomarkers that change with disease progression, including levels of phosphorylated and unphosphorylated tau protein and amyloid-beta-42. The project also investigated new imaging compounds which allow, for the first time, visualization of amyloid plaques and tau neurofibrillary tangles in the brain and how they change during disease progression.
Like the ADNI, both the PPMI and the PD-BIN could amass an enormous bio-bank of samples, which will be available without cost to scientists with approved research projects. In fact, Dr. Marek said, PPMI data sets will be maintained by the same lab that administers ADNI data: the Laboratory of Neuroimaging at the University of California, Los Angeles.
“In addition to accessing the data, researchers will be able to apply for PPMI's imaging and samples of CSF, blood, and urine from a biorepository we intend to maintain,” Dr. Marek said.
PPMI already has specific biomarkers targeted for research. Preliminary data indicate that alpha-synuclein, urate, and expression of the Parkinson's genetic marker DJ-1 change according to disease stage. Some data suggest that total tau, phosphorylated tau, and amyloid-beta might change as cognitive function is altered. Therefore, each of the 12 study visits will include blood, cerebrospinal fluid, urine, and DNA sampling as well as motor, neuropsychiatric, and cognitive assessments.
Both Dr. Hallett and Dr. Marek noted that the PPMI investigation and any others that join the federal program may uncover additional biomarkers. “The constant concern about looking for things that you know is that you might overlook something that you don't know, which could turn out to be something even better,” Dr. Hallett said.
Dr. Simuni has served as a consultant and received honorarium from GE Healthcare. She has received research support from the NIH and the Michael J. Fox Foundation. Dr. Marek is a member of the scientific advisory board for the Michael J. Fox Foundation and has been a consultant for Pfizer and GE Healthcare. He has an equity interest in Molecular NeuroImaging LLC. Dr. Hallet has no relevant disclosures.
PPMI will use single-photon emission CT scanning to track dopaminergic neurodegeneration in Parkinson's patients.
Source Courtesy Dr. John Seibyl, Institute for Neurodegenerative Disorders
How to Get Involved in PPMI
“Recruitment is the first, second, and third issue in a study like this,” said PPMI lead investigator Dr. Kenneth Marek. “We know we are asking a lot of our participants, but from what we have seen so far, a lot of patients with Parkinson's, and their friends and families who could be controls, understand the need for this approach and are willing and excited about participating in it.”
Both Dr. Marek and his coinvestigator Dr. Tanya Simuni admitted that the repeat lumbar punctures the study calls for could intimidate potential subjects. “It's important that they know that for most people, the possible side effects of a lumbar puncture are just about the same as for a blood draw,” Dr. Simuni said.
The first stop for information is the PPMI website,
By clicking on the “For Physicians” button, doctors can download the Physician Tool Kit, which includes brochures about the study; a poster; a pocket card with the study overview; and research referral forms (
www.ppmi-info.org/about/for-physicians
Researchers who are interested in working with biological samples from the study also can find information about submitting requests for potential projects (
