运动神经元疾病的突破性药物在新的研究中显示出希望

诸平

Key Highlights: Ellorarxine, a novel drug compound developed by Nevrargenics, has demonstrated antioxidant and anti-inflammatory effects, which make it a promising new therapy for treating ALS. The results showed that Ellorarxine increases MAP2 expression at low concentrations, induces neurite outgrowth, ameliorates neuroinflammation and modifies GluA2 expression. Nevrargenics is now proceeding to human trials with Ellorarxine, after receiving the green light from the MHRA.

据英国杜伦大学（Durham University）2024年10月22日提供的消息，运动神经元疾病的突破性药物在新的研究中显示出希望（Breakthrough drug for motor neurone disease shows promise in new study）。

根据2024年9月10日发表在《国际分子科学杂志》（International Journal of Molecular Sciences）上的一项研究——Olivia Escudier, Yunxi Zhang, Professor Andy Whiting, Professor Paul Chazot Evaluation of a Synthetic Retinoid, Ellorarxine, in the NSC-34 Cell Model of Motor Neuron Disease. International Journal of Molecular Sciences, 2024, 25(18): 9764. DOI: 10.3390/ijms25189764. https://www.mdpi.com/1422-0067/25/18/9764

此文报道了一种名为埃洛拉辛（Ellorarxine）的新药，为那些患有运动神经元疾病（motor neurone disease简称MND）的人带来了希望。来自杜伦大学化学系（Department of Chemistry, Science Laboratories, Durham University, Durham DH1 3LE, UK）和杜伦大学沃尔夫森健康与福利研究所生物科学系（Department of Biosciences, Wolfson Research Institute for Health and Wellbeing, Durham University, Durham DH1 3LE, UK）的研究人员合作研究发现，这种由Nevrargenics有限公司（Nevrargenics Ltd.）开发的新型化合物可以显著改善MND患者的神经元健康，增强他们神经系统的再生能力。

新的治疗方法解决了MND的多个方面（New treatment addresses multiple aspects of MND）

运动神经元疾病（MND）在任何时候都影响着英国超过5000人，其特征是进行性肌肉萎缩。目前的治疗方法只能解决症状，但埃洛拉辛显示出解决该疾病潜在原因的潜力。

研究表明，即使在非常低的浓度下，埃洛拉辛也具有抗氧化和抗炎作用。研究发现，它可以增加关键蛋白质的表达，促进神经突生长，改善线粒体健康——这些都是对抗MND的关键因素。

埃洛拉辛的与众不同之处在于它能够解决研究人员所谓的“3Ns”问题——神经保护（Neuroprotection）、神经可塑性（Neuroplasticity）和神经修复（Neurorepair）。这种综合方法在潜在的MND治疗中是罕见的，可能会改变该领域的游戏规则。

人体试验（Human trials）

这项研究的成功建立在英国阿伯丁大学(Aberdeen University)进行的早期研究的基础上，该研究表明，埃洛拉辛可以穿过血脑屏障并集中在脊髓中——这是任何有效治疗MND的关键特性。

有了这些有希望的结果，Nevrargenics有限公司已经获得了英国药品和保健产品监管机构（UK’s Medicines and Healthcare products Regulatory Agency简称MHRA）的批准，可以继续进行人体试验。

这标志着一种可能改变MND患者生活的治疗方法的发展向前迈出了重要一步。

上述介绍，仅供参考。欲了解更多信息，敬请注意浏览原文（full paper）或者相关报道。

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Ellorarxine enters human trials and shows promise for MND sufferers

Abstract

Amyotrophic lateral sclerosis (ALS) is the most common motor neuron disease worldwide and is characterized by progressive muscle atrophy. There are currently two approved treatments, but they only relieve symptoms briefly and do not cure the disease. The main hindrance to research is the complex cause of ALS, with its pathogenesis not yet fully elucidated. Retinoids (vitamin A derivatives) appear to be essential in neuronal cells and have been implicated in ALS pathogenesis. This study explores 4-[2-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydroquinoxalin-2-yl)ethylnyl]benzoic acid (Ellorarxine, or DC645 or NVG0645), a leading synthetic retinoic acid, discussing its pharmacological mechanisms, neuroprotective properties, and relevance to ALS. The potential therapeutic effect of Ellorarxine was analyzed in vitro using the WT and SOD1G93A NSC-34 cell model of ALS at an administered concentration of 0.3-30 nM. Histological, functional, and biochemical analyses were performed. Elorarxine significantly increased MAP2 expression and neurite length, increased AMPA receptor GluA2 expression and raised intracellular Ca²⁺ baseline, increased level of excitability, and reduced Ca²⁺ spike during depolarization in neurites. Ellorarxine also displayed both antioxidant and anti-inflammatory effects. Overall, these results suggest Ellorarxine shows relevance and promise as a novel therapeutic strategy for treatment of ALS.