Toward a Blood Test for Parkinson's Disease
March 6, 2012 — It may be possible to diagnose Parkinson's disease (PD) using disease-specific autoantibody profiles in blood, a new study suggests.
Using human protein microarrays, researchers identified 10 autoantibody biomarkers that can differentiate PD sera from healthy control sera as well as that from other diseases.
"Identification of blood-borne biomarkers for accurate diagnosis and early detection of PD has long been a major goal since this is required for early patient access to therapy," the study team notes. The current study identifies "autoantibody biomarkers that can detect the presence of PD with great sensitivity and specificity using only a small sample of blood."
Study investigator Robert Nagele, PhD, from the New Jersey Institute for Successful Aging, University of Medicine and Dentistry of New Jersey, Stratford, told Medscape Medical News, "A larger scale follow-up study is currently in progress and should be completed in March."
Disease-Specific Debris in Blood
Dr. Nagele and colleagues previously demonstrated the "ubiquitous presence" of autoantibodies in human sera, regardless of patient age or health status.
"We immediately suspected that this great number of autoantibodies is involved in the clearance of debris that is normally generated by the body on a day-to-day basis," Dr. Nagele said. "If true, we further predicted that the presence of a specific disease should generate an increased amount of disease-specific debris, which should induce an increased production of disease-specific autoantibodies that can be detected in the blood."
They recently reported that they detected disease-specific autoantibody biomarkers capable of differentiating blinded serum samples from Alzheimer's disease (AD) patients and control patients with a sensitivity of 96.0% and a specificity of 92.5%.
In their latest study, they used human protein microarrays to screen serum samples from 29 patients with PD, 50 with AD, and 40 healthy controls. They also screened serum samples from 30 patients with breast cancer and 10 with multiple sclerosis. The PD sample included patients with early, progressive, and last-stage disease.
The researchers identified 780 autoantibodies that had a significantly higher prevalence in the PD group than in the control group (P < .01), "and thus represent potential PD biomarkers." They selected the 10 autoantibody markers that demonstrated the largest difference in group prevalence between PD and controls to serve as diagnostic markers.
Table 1. Identity and Significance of 10 Potential Biomarkers for PD
Biomarker | Prevalence in PD (%) | Prevalence in Controls (%) |
ICAM4, transcript variant 1 | 93.55 | 2.38 |
PTCD2 | 90.32 | 7.14 |
FRMD8 | 87.10 | 4.76 |
Recombinant human CTLA-4/Fc | 87.10 | 14.29 |
Myotilin (MYOT) | 90.32 | 21.43 |
HSH2D | 87.10 | 7.14 |
Fibronectin 1 (FN1) | 90.32 | 14.29 |
TRIM21 | 80.65 | 9.52 |
Elongation factor 1-alpha 1 | 87.10 | 7.14 |
PABPC3 | 74.19 | 11.91 |
CTLA = cytotoxic T-lymphocyte antigen 4; FRMD8 = FERM domain containing 8; HSH2D = hematopoietic SH2 domain; ICAM4 = intercellular adhesion molecule 4; PABPC3 = poly(A) binding protein, cytoplasmic 3; PTCD2 = pentatricopeptide repeat domain 2; TRIM21 = tripartite motif-containing 21.
The researchers say these 10 autoantibodies correctly differentiated PD sera from control sera with a sensitivity of 93.1% and a specificity of 100%. PD sera were also distinguishable from sera obtained from AD, breast cancer, and multiple sclerosis patients, with accuracies of 86.0%, 96.6%, and 100%, respectively, they report.
"These results, combined with the previous work in which we demonstrated that PD can be distinguished from AD using only five autoantibody biomarkers…provide further confirmation that these biomarkers can be used to generate a specific and reliable PD diagnostic," the study team writes.
Summing up, Dr. Nagele said evidence continues to mount that neurodegenerative diseases such as PD and AD "may be detectable at an early stage with a simple test that requires only a single drop of blood. Early detection allows early treatment, which increases the likelihood that such treatments will be effective in curtailing the progress of the disease before too much devastation has occurred," he added.
"It also could greatly facilitate clinical trials investigating new potential medications by not only helping to enroll patients into the trials at an earlier stage of the disease, but also to monitor their progress while under treatment," Dr. Nagele said.
The study was supported by Foundation Venture Capital Group, LLC, an affiliate of the New Jersey Health Foundation. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. Dr. Nagele is founder of, and holds stock in, Durin Technologies, a company focusing on development of a blood test for AD. A coauthor is a paid consultant to Durin Technologies. The other 3 authors have disclosed no relevant financial relationships.
PLoS One. Published online February 22, 2012. Abstract
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