國家衛生研究院 NHRI:Item 3990099045/12729
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    題名: Tamoxifen for amyotrophic lateral sclerosis: A randomized double-blind clinical trial
    作者: Chen, PC;Hsieh, YC;Huang, CC;Hu, CJ
    貢獻者: NHRI Graduate Student Program
    摘要: INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is the most common cause of motor neuron disease, and effective treatment for ALS is still lacking. Transactive response (TAR) -DNA-binding protein-43 (TDP-43) is aggregated in the neurons of ALS patients. Animal studies shown TDP-43 aggregation can be attenuated by enhancing autophagy by tamoxifen. However, its beneficial effects for ALS patients remain unknown. METHODS: Eighteen patients with ALS without mutations in superoxide dismutase-1 (SOD-1) or fused in sarcoma (FUS) genes were randomly assigned into the tamoxifen 40 mg/day or placebo group in a double-blinded manner and all were given riluzole twice daily. Participants were followed up at 1, 3, 6, and 12 months. The primary end point was time to death or dependence on mechanical ventilation. Secondary end points were decline of the revised ALS Functional Rating Scale (ALSFRS-R) score and pulmonary function measured by forced vital capacity (FVC). RESULTS: Ten participants were randomly assigned in the treatment group with tamoxifen, 7 finished trial, 1 reach primary endpoint; while 8 participants in the placebo group, 2 finished trial and 2 reach primary end point. The proportion of participants reaching the primary end point was lower in the tamoxifen group but did not reach statistical significance. At the 1-, 3-, and 6-month follow-up, the average decline rates of the ALSFRS-R score were slower in the tamoxifen group. No significant difference was observed in FVC and ALSFRS-R score at 12 months between groups. CONCLUSION: Tamoxifen exerted only a modest effect on attenuate progression for 6 months in this small trial. Additional larger scale studies should be necessary to confirm whether enhancing autophagy can attenuate ALS progression.
    日期: 2020-05-29
    關聯: Medicine. 2020 May 29;99(22):Article number e20423.
    Link to: http://dx.doi.org/10.1097/MD.0000000000020423
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0025-7974&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000551511100085
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85085677164
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