The BioFIND study: Characteristics of a clinically typical Parkinson's disease biomarker cohort

Abstract

Background Identifying PD-specific biomarkers in biofluids will greatly aid in diagnosis, monitoring progression, and therapeutic interventions. PD biomarkers have been limited by poor discriminatory power, partly driven by heterogeneity of the disease, and variability of collection protocols, and focus on de novo, un-medicated patients. Thus, a platform for biomarker discovery and validation in well-characterized, clinically typical, moderate to advanced PD cohorts is critically needed. Methods BioFIND (Fox Investigation for New Discovery of Biomarkers in Parkinson’s Disease) is a cross-sectional, multi-center biomarker study that established a repository of clinical data, blood, DNA, RNA, CSF, saliva and urine samples from 118 moderate to advanced PD and 88 healthy control subjects. Inclusion criteria were designed to maximize diagnostic specificity by selecting participants with clinically typical PD symptoms, and clinical data and biospecimen collection utilized standardized procedures to minimize variability across sites. Results We present the study methodology and data on the cohort’s clinical characteristics. Motor scores and biospecimen samples including plasma are available for practically defined “off” states and “on” states and thus enable testing the effects of PD medications on biomarkers. Other biospecimens are available from “off” state PD assessments and from controls. Conclusion Our cohort provides a valuable resource for biomarker discovery and validation in PD. Clinical data and biospecimens, available through The Michael J. Fox Foundation for Parkinson’s Research and the National Institute of Neurological Disorders and Stroke, can serve as a platform for discovering biomarkers in clinically typical PD and comparisons across PD’s broad and heterogeneous spectrum.

Comparative study of cerebrospinal fluid α‐synuclein seeding aggregation assays for diagnosis of Parkinson's disease

“…Additionally, HC subjects with any first‐degree family member with PD were excluded to reduce the chance of enrolling prodromal cases. Additional details regarding the cohort are discussed in the original manuscript detailing the BioFIND study …”

“…All subjects either fasted or consumed a low‐fat diet on the morning of V2 at the time of biospecimen collection. CSF was immediately frozen in a –80 ° C freezer and shipped to the biorepository on dry ice at a later date . Data collected included demographics, family history of PD, medical/neurological histories, medications, neurological exams, the MDS‐UPDRS, MoCA, and REM Behavior Sleep Disorder (RBD) Questionnaire and, for PD subjects, the Modified Schwab and England Activities of Daily Living Scale…”

“…Therefore, we undertook a blinded study of two similar assays that were separately developed by independent laboratories. These two platforms tested CSF from the same subjects in the BioFIND cohort, which utilized standardized biospecimen collection protocols of clinically typical and well‐defined moderate PD patients and healthy controls …”

Hoehn and Yahr stage 3 and postural stability item in the movement disorder society–unified Parkinson's disease rating scale

“…Therefore, we hypothesized that clinical researchers might be grading patients as H&Y stage ≥ 3 exclusively based on the observed PS scores indicating the absence of postural response. We examined the medication off‐state data from the Parkinson Progression Markers Initiative (PPMI) and The Fox Investigation for New Discovery of Biomarkers (BioFIND) to test this hypothesis. We found that for patients with H&Y stage < 3, only 1 patient had a PS score = 3 in the MDS‐UPDRS (Fig.…”

The importance of an independent validation cohort for metabolomics biomarker studies

“…In addition to others, BioFIND collected CSF according to standardized operating procedures similar to ours, but in well‐defined, moderately advanced individuals with PD (MDS‐UPDRS motor score, 39) and control volunteers. The cohort includes PD patients with a disease duration between 5 and 18 years after symptom onset who have already been treated with PD medication . In contrast, participants from our DeNoPa cohort were all recently diagnosed and were de novo at the time of lumbar puncture, with a mean MDS‐UPDRS motor score of 21 .…”