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, Dr. Mark Hallett, chief of NINDS’ Medical Neurology branch and its Human Motor Control Section, anticipated that the project could be up and running within 1 year.
“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.
“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. “We want all our data to be available to researchers on an ongoing basis, and we encourage them to come up with their own research ideas based on PPMI data.”
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.
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. Marek agreed. “The biomarkers we’re looking at are based on existing scientific data. But the PPMI study is a mix of what we know now and what we hope will happen – finding things we don’t yet know about.”
“Recruitment is the first, second, and third issue in a study like this,” said Dr. 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. 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. From here, physicians, researchers, and participants can learn about the scope of the project, the inclusion and exclusion criteria, and even see a schedule of visits and tests that each participant will need to fulfill.