A Longitudinal Program for Biomarker Development in Parkinson’s Disease: A Feasibility Study
Ravina, B., Tanner, C., DiEuliis, D., Eberly, S., Flagg, E., Galpern, W.R., Fahn, S., Goetz, C.G., Grate, S., Kurlan, R., Lang, A.E., Marek, K., Kieburtz, K., Oakes, D., Elliott, R., Shoulson, I., Parkinson Study Group LAPBS-PD Investigators. A Longitudinal Program for Biomarker Development in Parkinson’s Disease: A Feasibility Study , Movement Disorders, 24(14): 2081-90
Background of the Study
When it comes to Parkinson’s disease (PD), patient follow-up is crucial to provide longterm data that can help to predict symptoms of PD and develop therapies to treat or prevent them. Longterm data is also valuable for developing PD biomarkers, specific biological traits used to indicate PD severity or progression. Unfortunately, few studies have attempted to monitor patients for more than five years, since it is costly and difficult to maintain the follow-up of any participant study group.
To address these setbacks, a nonprofit association of researchers known as the Parkinson’s Study Group (PSG) developed the Longitudinal and Biomarker Studies in Parkinson’s Disease (LABS-PD), a program designed to re-recruit groups of PD patients from earlier studies and evaluate them through their disease in order to:
- Provide longterm data on the course of PD symptoms
- Develop biomarkers that measure risk for and progression of PD.
Accordingly, an initial feasibility study conducted by PSG researchers and published in the Movement Disorders Journal (Vol. 24, Issue 14), establishes that LABS-PD is a promising strategy to assess PD study groups over time and to provide a platform for biomarker development.
Purpose of the Study
The purpose of this study was to test the program’s feasibility by evaluating patient enrollment and biomarker sampling in the first LABS-PD study groups.
LABS-PD Participants and Study Groups:
The first participant study groups formed in LABS-PD were:
- A large group of PD patients
- A second group of control subjects including:
- Healthy controls: Participants who do not have PD.
- Disease controls: Participants with other neurological disorders that resemble PD.
In executing the study, researchers used the following methods:
Firstly, in order to create the program’s first study groups, researchers enrolled participants by:
- Inviting patients and research sites from PRECEPT (a former PD drug trial) to participate in PostCEPT—the firstPD study group in LABS-PD
- Inviting healthy and disease controls to join the control group for the Prognostic Biomarkers (PROBE) study, a LABS-PD study that collects four different patient biological samples in order to analyze their potential as PD biomarkers.
Next, in order to obtain patient medical data and track the natural course of PD, researchers used the following methods to follow up on PostCEPT patients:
- Researchers met with patients annually and at 3-year intervals to evaluate progression of motor and non-motor symptoms of PD and changes in cognition and behavior
- FOUND Study: Researchers invited patients to participate in the Follow-up of Persons with Neurologic Diseases (FOUND) study, a LABS-PD clinical study that conducts mail and telephone follow-up to update: patient diagnosis, medications, hallucinations, fatigue, sleep disorders, use of health care services, available social supports, and the economic impact of Parkinson’s.
Afterwards, to provide a biological database to help study and develop PD biomarkers, researchers established three means to collect PostCEPT biological samples and patient data:
- Blood Samples: Patients were invited to donate blood samples to a DNA repository, where their cell samples were prepped and preserved to provide a source of DNA.
- Imaging Study: Patients were invited to continue the PRECEPT drug trial’s DAT imaging study, where patients received a series of brain imaging scans to monitor dopamine-related damage.
- PROBE Study: Patients were invited to participate in the LABS-PD Prognostic Biomarkers (PROBE) study, where researchers collected four different patient biological samples to analyze their potential as PD biomarkers.
Lastly, in order to manage LABS-PD data and link patient data from earlier studies (ex. PRECEPT) to patient data collected during LABS-PD, researchers used the following methods:
- Researchers developed a unique identifier system that provides each patient with a special ID so that s/he can be tracked across multiple studies without being personally identified
- Researchers created the PD-DOC website (a public-access website of clinical, environmental, and biological patient data) so that new LABS-PD data can be readily stored and accessed.
In response to the program’s feasibility, this study suggests that LABS-PD is a promising strategy to assess PD study groups longterm and to support the development of PD biomarkers. This suggestion was based on statistical analyses evaluating enrollment in the first LABS-PD study groups and participation in the program’s clinical studies and biomarker sampling procedures.
In terms of LABS-PD study group enrollment, researchers found that:
- Over two-thirds, 67% (537 of 806), of all PRECEPT patients were recaptured for the PostCEPT study group
- Over 100 subjects (54 healthy controls, 53 disease controls) were recruited for the Prognostic Biomarkers (PROBE) control study group.
According to these results, researchers determined that LABS-PD is a feasible way to offer patients the opportunity for longterm study participation and to enroll participants for the purpose of developing PD biomarkers. Moreover, after comparing data from PRECEPT to PostCEPT enrollment, researchers discovered no significant difference between patients who enrolled in PostCEPT and patients who did not enroll in PostCEPT. This discovery suggests that enrollment was not based on demographic differences (ex. age, gender, and race) or on the severity of PD symptoms.
Furthermore, in terms of participation in LABS-PD clinical studies and biomarker sampling procedures, researchers found that:
- Blood Samples: 72% of PostCEPT patients have donated blood samples to the DNA repository.
- Imaging Study: 95% of PostCEPT patients have received follow-up imaging scans under the DAT imaging study.
- PROBE Study: 100% of PROBE participants (102 PostCEPT patients, 107 control subjects) have completed biomarker processing for all four biological samples.
- FOUND Study: 51 of 55 PostCEPT sites—and 92% (454 of 489) of their patients—have agreed to participate in the Follow-up of Persons with Neurological Diseases (FOUND) study.
According to these findings, researchers concluded that LABS-PD is a feasible strategy to provide longterm patient data and to collect a variety of patient biological samples for biomarker study.
Study Discussion & Implications
The concept of LABS-PD is significant because it represents the potential to attain longterm patient data, which is critical to understanding Parkinson’s and how the disease evolves in patients. Such a milestone in understanding of the nature of PD would enable researchers to predict complications of the disease and develop therapies to prevent them. Overall, the study indicates that the LABS-PD program is a feasible strategy to support the longterm assessment of PD study groups and to provide a foundation for biomarker development. Based on the study results and the success of the initial LABS-PD efforts, researchers recommend that the program is put into full operation; continuing to enroll additional study groups to increase patient diversity and continuing to identify promising biomarkers that will track the course of PD.