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Creation of a gene expression classifier for predicting Parkinson's disease rate of progression.
J Neural Transm (Vienna). 2020 05; 127(5):755-762.JN

Abstract

Parkinson's disease (PD) etiology is heterogeneous, genetic, and multi-factorial, resulting in a varied disease from a mild slow progression to a more severe rapid progression. Prognostic information on the nature of the patient's disease at diagnosis aids the physician in counseling patients on treatment options and life planning. In a cohort of PD patients from the PPMI study, the relative gene expression levels of SKP1A, UBE2K, ALDH1A1, PSMC4, HSPA8 and LAMB2 were measured in baseline blood samples by real-time quantitative PCR. At baseline PD patients were up to 2 years from diagnosis, H&Y scale ≤ 2 and PD treatment naïve. PD-Prediction algorithm comprised of ALDH1A1, LAMB2, UBE2K, SKP1A and age was created by logistic regression for predicting progression to ≤ 70% Modified Schwab and England Activities of Daily Living (S&E-ADL). In relation to patients negative for PD-Prediction (n = 180), patients positive (n = 30) for Cutoff-1 (at 82% specificity, 80.0% sensitivity) had positive hazard ratio (HR+) of 10.6 (95% CI, 2.2-50.1), and positive (n = 23) for Cutoff-2 (at 93% specificity, 47% sensitivity) had HR+ of 17.1 (95% CI, 3.2-89.9) to progress to ≤ 70% S&E-ADL within 3 years (P value < 0.0001). Likewise, patients positive for PD-Prediction Cutoff-1 (n = 49) had HR+ 4.3 (95% CI, 1.6-11.6) for faster time to H&Y 3 in relation to patients negative (n = 170) for PD-Prediction (P value = 0.0002). Our findings show an algorithm that seems to predict fast PD progression and may potentially be used as a tool to assist the physician in choosing an optimal treatment plan, improving the patient's quality of life and overall health outcome.

Authors+Show Affiliations

BioShai Ltd., 1 Ha-Tsmikha St., Yokneam, Israel. Jmrabey@yahoo.com. Sackler School of Medicine, Tel Aviv University, 6997801, Tel Aviv, Israel. Jmrabey@yahoo.com.BioShai Ltd., 1 Ha-Tsmikha St., Yokneam, Israel.BioShai Ltd., 1 Ha-Tsmikha St., Yokneam, Israel.BioShai Ltd., 1 Ha-Tsmikha St., Yokneam, Israel.BioShai Ltd., 1 Ha-Tsmikha St., Yokneam, Israel. Clinic and Policlinic for Psychiatry, Psychosomatics and Psychotherapy, University Hospital Wuerzburg, Margarete-Hoeppel-Platz 1, 97080, Wuerzburg, Germany. University of Southern Denmark Odense, J.B. Winslows Vey 18, 5000, Odense, Denmark.BioShai Ltd., 1 Ha-Tsmikha St., Yokneam, Israel. Faculty of Medicine, Technion-Israel Institute of Technology, 31096, Haifa, Israel.

Pub Type(s)

Journal Article
Multicenter Study
Observational Study
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

32385576

Citation

Rabey, Jose Martin, et al. "Creation of a Gene Expression Classifier for Predicting Parkinson's Disease Rate of Progression." Journal of Neural Transmission (Vienna, Austria : 1996), vol. 127, no. 5, 2020, pp. 755-762.
Rabey JM, Yarden J, Dotan N, et al. Creation of a gene expression classifier for predicting Parkinson's disease rate of progression. J Neural Transm (Vienna). 2020;127(5):755-762.
Rabey, J. M., Yarden, J., Dotan, N., Mechlovich, D., Riederer, P., & Youdim, M. B. H. (2020). Creation of a gene expression classifier for predicting Parkinson's disease rate of progression. Journal of Neural Transmission (Vienna, Austria : 1996), 127(5), 755-762. https://doi.org/10.1007/s00702-020-02194-y
Rabey JM, et al. Creation of a Gene Expression Classifier for Predicting Parkinson's Disease Rate of Progression. J Neural Transm (Vienna). 2020;127(5):755-762. PubMed PMID: 32385576.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Creation of a gene expression classifier for predicting Parkinson's disease rate of progression. AU - Rabey,Jose Martin, AU - Yarden,Jennifer, AU - Dotan,Nir, AU - Mechlovich,Danit, AU - Riederer,Peter, AU - Youdim,Moussa B H, Y1 - 2020/05/08/ PY - 2020/02/21/received PY - 2020/04/16/accepted PY - 2020/5/10/pubmed PY - 2020/5/10/medline PY - 2020/5/10/entrez KW - Biomarker KW - Gene expression classifier KW - Hoehn and Yahr KW - Modified Schwab and England Activities of Daily Living KW - Parkinson’s disease KW - Prognosis SP - 755 EP - 762 JF - Journal of neural transmission (Vienna, Austria : 1996) JO - J Neural Transm (Vienna) VL - 127 IS - 5 N2 - Parkinson's disease (PD) etiology is heterogeneous, genetic, and multi-factorial, resulting in a varied disease from a mild slow progression to a more severe rapid progression. Prognostic information on the nature of the patient's disease at diagnosis aids the physician in counseling patients on treatment options and life planning. In a cohort of PD patients from the PPMI study, the relative gene expression levels of SKP1A, UBE2K, ALDH1A1, PSMC4, HSPA8 and LAMB2 were measured in baseline blood samples by real-time quantitative PCR. At baseline PD patients were up to 2 years from diagnosis, H&Y scale ≤ 2 and PD treatment naïve. PD-Prediction algorithm comprised of ALDH1A1, LAMB2, UBE2K, SKP1A and age was created by logistic regression for predicting progression to ≤ 70% Modified Schwab and England Activities of Daily Living (S&E-ADL). In relation to patients negative for PD-Prediction (n = 180), patients positive (n = 30) for Cutoff-1 (at 82% specificity, 80.0% sensitivity) had positive hazard ratio (HR+) of 10.6 (95% CI, 2.2-50.1), and positive (n = 23) for Cutoff-2 (at 93% specificity, 47% sensitivity) had HR+ of 17.1 (95% CI, 3.2-89.9) to progress to ≤ 70% S&E-ADL within 3 years (P value < 0.0001). Likewise, patients positive for PD-Prediction Cutoff-1 (n = 49) had HR+ 4.3 (95% CI, 1.6-11.6) for faster time to H&Y 3 in relation to patients negative (n = 170) for PD-Prediction (P value = 0.0002). Our findings show an algorithm that seems to predict fast PD progression and may potentially be used as a tool to assist the physician in choosing an optimal treatment plan, improving the patient's quality of life and overall health outcome. SN - 1435-1463 UR - https://www.unboundmedicine.com/medline/citation/32385576/Creation_of_a_gene_expression_classifier_for_predicting_Parkinson's_disease_rate_of_progression_ L2 - https://doi.org/10.1007/s00702-020-02194-y DB - PRIME DP - Unbound Medicine ER -