抗逆转录病毒治疗的肌萎缩侧索硬化症患者中 HERV-K（HML-2）的抑制作用。

Inhibition of HERV-K (HML-2) in amyotrophic lateral sclerosis patients on antiretroviral therapy.

机构信息

Section of Infections of the Nervous System, National Institute of Neurological Disorders and Stroke, Bethesda, MD. USA.

Department of Clinical Medicine, Macquarie University Centre for Motor Neuron Disease Research, Australia.

出版信息

J Neurol Sci. 2021 Apr 15;423:117358. doi: 10.1016/j.jns.2021.117358. Epub 2021 Feb 23.

DOI:10.1016/j.jns.2021.117358

PMID:33653604

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8009857/

Abstract

Reactivation of Human Endogenous Retrovirus K (HERV-K), subtype HML-2, has been associated with pathophysiology of amyotrophic lateral sclerosis (ALS). We aimed to assess the efficacy of antiretroviral therapy in inhibiting HML-2 in patients with ALS and a possible association between the change in HML-2 levels and clinical outcomes. We studied the effect of 24-weeks antiretroviral combination therapy with abacavir, lamivudine, and dolutegravir on HML-2 levels in 29 ALS patients. HML-2 levels decreased progressively over 24 weeks (P = 0.001) and rebounded within a week of stopping medications (P = 0.02). The majority of participants (82%), defined as "responders", experienced a decrease in HML-2 at week 24 of treatment compared to the pre-treatment levels. Differences in the evolution of some of the clinical outcomes could be seen between responders and non-responders: FVC decreased 23.69% (SE = 11.34) in non-responders and 12.71% (SE = 8.28) in responders. NPI score decreased 91.95% (SE = 6.32) in non-responders and 53.05% (SE = 10.06) in responders (P = 0.01). Thus, participants with a virological response to treatment showed a trend for slower progression of the illness. These findings further support the possible involvement of HML-2 in the clinical course of the disease.

摘要

人类内源性逆转录病毒 K（HERV-K）亚型 HML-2 的激活与肌萎缩侧索硬化症（ALS）的病理生理学有关。我们旨在评估抗逆转录病毒疗法抑制 ALS 患者中 HML-2 的疗效，以及 HML-2 水平变化与临床结局之间的可能关联。我们研究了 29 例 ALS 患者接受 24 周联合抗逆转录病毒治疗（阿巴卡韦、拉米夫定和度鲁特韦）对 HML-2 水平的影响。在 24 周内，HML-2 水平逐渐下降（P=0.001），停药后一周内反弹（P=0.02）。大多数参与者（82%），定义为“应答者”，与治疗前相比，在治疗第 24 周时 HML-2 水平下降。应答者和无应答者之间可以看到一些临床结局的演变差异：无应答者的 FVC 下降 23.69%（SE=11.34），而应答者下降 12.71%（SE=8.28）。无应答者的 NPI 评分下降 91.95%（SE=6.32），而应答者下降 53.05%（SE=10.06）（P=0.01）。因此，对治疗有病毒学反应的参与者显示出疾病进展较慢的趋势。这些发现进一步支持 HML-2 可能参与疾病的临床过程。