{“_”：“[肌萎缩侧索硬化症（ALS）新药Mecobalamin（Rozebalin）肌肉注射25mg的作用机制和临床试验结果]。”，“sup”：[“®”]}

摘要(中文译文)

肌萎缩侧索硬化（ALS）是一种进行性、难治性神经退行性疾病，以全身性肌萎缩和肌无力、构音障碍、吞咽困难及呼吸肌麻痹为特征。肌无力导致的呼吸功能障碍是主要死因；若不使用机械通气，通常在发病后2至5年内死亡。甲钴胺是维生素B的一种活性形式，被认为可通过作为甲硫氨酸合成酶的辅酶，催化同型半胱氨酸转化为甲硫氨酸，从而抑制同型半胱氨酸诱导的ALS神经元细胞死亡。自20世纪90年代以来，日本厚生劳动省支持的神经退行性疾病研究表明，高剂量甲钴胺可能对ALS具有临床获益。这促成了临床开发的启动。一项II/III期双盲、安慰剂对照比较试验已开展，但未达到其主要终点。基于这些试验结果，一项由研究者发起的III期安慰剂对照、双盲比较试验主要在德岛大学医院开展， targeting 在开始试验前一年内发病的ALS患者。该试验证实了高剂量甲钴胺在延缓修订版ALS功能评定量表总分下降方面的疗效，该评分为主要终点。安全性亦得到确认。基于这些结果，甲钴胺于2024年9月获得监管批准，适应证为“延缓ALS功能损害的进展”。预计它将为ALS患者提供一种新的治疗选择。

Abstract

Amyotrophic lateral sclerosis (ALS) is a progressive, intractable neurodegenerative disease characterized by generalized muscle atrophy and weakness, dysarthria, dysphagia, and respiratory muscle paralysis. Respiratory dysfunction due to muscle weakness is the primary cause of death; without mechanical ventilation, death typically occurs within 2 to 5 years after onset. Mecobalamin, an active form of vitamin B, is thought to suppress homocysteine-induced neuronal cell death in ALS by acting as a coenzyme for methionine synthase, which catalyzes the conversion of homocysteine to methionine. Since the 1990s, research on neurodegenerative diseases supported by Japan's Ministry of Health, Labour and Welfare has suggested that high-dose mecobalamin may confer clinical benefits in ALS. This led to the initiation of clinical development. A Phase II/III double-blind, placebo-controlled comparative trial was conducted, but did not meet its primary endpoint. Based on these trial findings, an investigator-initiated Phase III placebo-controlled, double-blind comparative trial was conducted primarily at Tokushima University Hospital, targeting patients who developed ALS within one year before starting the trial. The trial demonstrated the efficacy of high-dose mecobalamin in slowing the decline in the Revised ALS Functional Rating Scale total score, which was the primary endpoint. Safety was also confirmed. Based on these results, mecobalamin received regulatory approval in September 2024 for the indication "slowing the progression of functional impairment in ALS." It is expected to offer a new treatment option for patients with ALS.

如何引用