“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), which also is a public-private collaboration. Launched in 2004, the ADNI studied the rate of change of cognition, brain structure and function, and biomarkers in healthy control patients, patients with mild cognitive impairment, and patients with Alzheimer's disease. Discoveries made through the ADNI 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.
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.
Single-photo emission CT with DaTSCAN (ioflupane [123I]) and MRI imaging will determine changes in brain structure and dopamine levels. Although not yet approved for clinical use in the United States, the DaTSCAN radioisotope binds to dopamine transporters in the substantia nigra, allowing researchers to study dopaminergic neurodegeneration.
Dr. Simuni has served as a consultant and received honorarium from GE Healthcare, which manufactures and markets DaTSCAN in Europe. She has received research support from the NIH and the Michael J. Fox Foundation.
Dr. Marek is on the scientific advisory board of 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 Join the Biomarker Search
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,” she said.
The first stop for information is the PPMI Web site,
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 (
www.ppmi-info.org/for-researchers
The site contains a wealth of information for patients and families as well (