Private and public sources are launching two massive efforts to identify biomarkers for Parkinson's disease – an effort they say will speed drug research, providing more efficient ways to track disease progress and monitor therapeutic response.
In late September, the Michael J. Fox Foundation kicked off its Parkinson's Progression Markers Initiative (PPMI) and the National Institute for Neurological Disorders and Stroke sent out a request for applications to create the Parkinson's Disease Biomarker Identification Network (PD-BIN). The 5-year PPMI is the first large-scale clinical study to focus exclusively on identifying and validating both chemical and imaging biomarkers of the disease. The multiproject PD-BIN will be similarly devoted to identifying biological markers that contribute to an individual's risk for Parkinson's disease, as well as its onset and progression, with the goal of speeding disease-modifying treatments.
“We expect that the biomarkers we discover will help us better understand the disease and accelerate therapeutic trials, with the goal of assessing whether a drug can modify the progression of Parkinson's,” PPMI primary investigator Dr. Kenneth Marek said in an interview. “In a way, this is much more complex than a clinical treatment trial. We are not testing a drug, but ideally, we will find markers that can pave the way to accomplish more effective drug testing.”
Speaking from the World Parkinson Congress in Glasgow, Scotland, where he unveiled the PPMI to the scientific community, Dr. Marek stressed the need for objective, measurable disease markers in diagnosis and disease progression, as well as in research studies. The diagnosis of Parkinson's disease remains solely based on clinical signs and symptoms, with no concrete diagnostic measure. Progression, as well, can be measured only by the worsening of symptoms. And with no objective clinical measurements in hand, researchers are “shooting in the dark” when assessing response to candidate drugs, he said.
“We have been conducting these clinical trials, but we there is no way to assess when a drug is ineffective,” said Dr. Marek, who also is president of the Institute for Neurodegenerative Disorders in New Haven, Conn.
Having a set of biomarkers will speed research in a way that is not now possible, said PPMI co-investigator Dr. Tanya Simuni, director of the Parkinson's Disease and Movement Disorders Center at Northwestern University, Chicago.
“We have many ongoing clinical trials of potential disease-modifying agents, but they are slow to progress because clinical assessment is the primary efficacy measure,” Dr. Simuni said in an interview. “Because of this, these studies take a long time and need a large number of patients – and they still sometimes end up with inconclusive results.” An objective measure of disease progression, would speed drug development by reducingthtudy duration and sizeof he said.
The discovery of a biomarker could also help clinicians identify patients in the earliest – perhaps even prodromal – disease state, she said. “By the time symptoms of Parkinson's appear, patients can have lost up to 70% of their dopamine-producing cells, which tells us that there is a prodromal or preclinical phase during which damage is occurring without clinical signs. Biomarkers could not only help us develop better interventions but also screening tools.”
The PPMI will be conducted at 14 U.S. centers and at centers in Innsbruck, Austria; Kassel and Tubingen, Germany; and Naples, Italy. It aims to recruit 200 healthy control patients and 400 patients newly diagnosed with Parkinson's disease who are not yet receiving medication.
The absence of Parkinson's disease medications is one key to a successful biomarker hunt, said Dr. Simuni, the principal investigator for the Midwestern region of the United States. “We want to make sure there is no over-signal of the therapy – that we are looking at the progression of disease unmasked by interventions.”
This should not be a problem with this patient population – at least initially. “For many patients with a new diagnosis, symptoms don't interfere with their function, so it's quite common not to start treatment at this time,” Dr. Simuni said. “At the point when the patient needs treatment, of course, it will start. They can remain in the study and count toward the follow-up. But our aim is to recruit patients early enough that we get at least 6 months of data without medication.”
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 (http://grants.nih.gov/grants/guide/rfa-files/RFA-NS-11-005.html