In‐depth analysis of data from the RAS‐ALS study reveals new insights in rasagiline treatment for amyotrophic lateral sclerosis

Author:

Schuster Joachim12ORCID,Dreyhaupt Jens3,Mönkemöller Karla4,Dupuis Luc5,Dieterlé Stéphane5,Weishaupt Jochen H.6,Kassubek Jan12ORCID,Petri Susanne7,Meyer Thomas8ORCID,Grosskreutz Julian9,Schrank Berthold10,Boentert Matthias11,Emmer Alexander12,Hermann Andreas1314,Zeller Daniel15ORCID,Prudlo Johannes1416,Winkler Andrea S.17,Grehl Torsten18,Heneka Michael T.19,Johannesen Siw20,Göricke Bettina21,Witzel Simon1ORCID,Dorst Johannes1ORCID,Ludolph Albert C.12,

Affiliation:

1. Department of Neurology University of Ulm Ulm Germany

2. German Center for Neurodegenerative Diseases Ulm Germany

3. Institute of Epidemiology and Medical Biometry University of Ulm Ulm Germany

4. Department of Clinical and Health Psychology, Institute of Education and Psychology University of Ulm Ulm Germany

5. Université de Strasbourg Inserm, UMR‐S1118, Centre de Recherches en biomédecine de Strasbourg Strasbourg France

6. Division of Neurodegeneration, Department of Neurology, Mannheim Center for Translational Neurosciences, Medical Faculty Mannheim Heidelberg University Mannheim Germany

7. Department of Neurology Hannover Medical School Hannover Germany

8. Department of Neurology, Center for ALS and other Motor Neuron Disorders Charité–Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt‐Universität zu Berlin, and Berlin Institute of Health Berlin Germany

9. Department of Neurology University Clinic Schleswig‐Holstein, Campus Lübeck Lübeck Germany

10. Department of Neurology DKD HELIOS Klinik Wiesbaden Wiesbaden Germany

11. Department of Neurology University Hospital Münster Münster Germany

12. Department of Neurology University Hospital Halle Halle Germany

13. Translational Neurodegeneration Section “Albrecht Kossel,” Department of Neurology University Medical Center Rostock Rostock Germany

14. German Center for Neurodegenerative Diseases, Rostock/Greifswald Rostock Germany

15. Department of Neurology University of Würzburg Würzburg Germany

16. Department of Neurology Rostock University Medical Center Rostock Germany

17. Department of Neurology Technical University Munich Munich Germany

18. Department of Neurology Alfried Krupp Hospital Essen Germany

19. Luxembourg Center for Systems Biomedicine University of Luxembourg Belval Luxembourg

20. Neurology BG Hospital Murnau Murnau Germany

21. Department of Neurology University Hospital of Göttingen Göttingen Germany

Abstract

AbstractBackground and purposeIn 2016, we concluded a randomized controlled trial testing 1 mg rasagiline per day add‐on to standard therapy in 252 amyotrophic lateral sclerosis (ALS) patients. This article aims at better characterizing ALS patients who could possibly benefit from rasagiline by reporting new subgroup analysis and genetic data.MethodsWe performed further exploratory in‐depth analyses of the study population and investigated the relevance of single nucleotide polymorphisms (SNPs) related to the dopaminergic system.ResultsPlacebo‐treated patients with very slow disease progression (loss of Amyotrophic Lateral Sclerosis Functional Rating Scale–Revised [ALSFRS‐R] per month before randomization of ≤0.328 points) showed a per se survival probability after 24 months of 0.85 (95% confidence interval = 0.65–0.94). The large group of intermediate to fast progressing ALS patients showed a prolonged survival in the rasagiline group compared to placebo after 6 and 12 months (p = 0.02, p = 0.04), and a reduced decline of ALSFRS‐R after 18 months (p = 0.049). SNP genotypes in the MAOB gene and DRD2 gene did not show clear associations with rasagiline treatment effects.ConclusionsThese results underline the need to consider individual disease progression at baseline in future ALS studies. Very slow disease progressors compromise the statistical power of studies with treatment durations of 12–18 months using clinical endpoints. Analysis of MAOB and DRD2 SNPs revealed no clear relationship to any outcome parameter. More insights are expected from future studies elucidating whether patients with DRD2CC genotype (Rs2283265) show a pronounced benefit from treatment with rasagiline, pointing to the opportunities precision medicine could open up for ALS patients in the future.

Funder

Teva Pharmaceutical Industries

Publisher

Wiley

Subject

Neurology (clinical),Neurology

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3