肌萎縮性脊髓側索硬化症(amyotrophic lateral sclerosis, ALS)，是一種退化性且不可逆的疾病。ALS會產生腦部的上運動神經元，與脊髓腦幹的下運動神經元的漸進性退化。常見的症狀有肌肉無力、萎縮、吞嚥及呼吸困難等。平均發病後的存活時間為5-6年。台灣ALS的平均發生率約為10萬分之0.6，平均發病年齡為52.5歲。目前ALS只有2種藥物，Riluzole及Edaravone，是經過美國食品藥物管理局核准的，但效果都相當有限。因此，許多研究團隊正積極瞭解ALS的致病機轉並據以設計相對應的治療藥物，而ALS致病基因的研究是其中一個重要的方向。迄今已有超過40個ALS相關的致病基因被發現。以標靶治療的概念，目前有多種針對特定基因型的試驗藥物，正進行臨床試驗中。其中進展最快的Tofersen是SODi基因的反義核苷酸(antisense oligonucleotide, ASO)，其作用原理是透過藥物與SODi基因所產生的信使RNA(messenger RNA)結合，促進其分解，藉此減少的突變蛋白產量。Tofersen已於2021年完成3期臨床試驗，雖然無法顯著改善ALS患者的整體功能，但可以有效降低腦脊鶴液内的或血液中輕鏈神經纖維(neurofilament light, Nfl)蛋白量。其他針對不同基因的試驗療法，目前也在積極進行臨床試驗中。希望在不久的將來，帶有常見基因突變的ALS患者，將有機會接受相應的基因標靶治療。

Amyotrophic lateral sclerosis (ALS) is an irreversible neurodegenerative disease. ALS results in progressive degeneration of upper motor neurons in the brain as well as lower motor neurons in the brainstem and spinal cord. Common symptoms of ALS include muscle weakness and atrophy, dysarthria and difficulties in breathing and swallowing. Most of the patients affected by ALS die within 5-6 years after disease onset. In Taiwan, the incidence of ALS is 0.6 over 100,000 and average age of onset is 52.5 years. Currently, there are only two FDA-approved medications for ALS, namely Riluzole and Edaravone but their efficacies are limited. As a result, researchers are investigating the pathogenic mechanisms of ALS, hoping to design targeted medications accordingly. Researches focusing on the diseases-causing genes are among top priorities. To date, more than 40 ALS-associated genes have been discovered. There are multiple clinical trials testing novel targeted therapeutics that designed for carriers of specific disease genes. The leading experimental drug Tofersen is an antisense oligonucleotide. It targets the messenger RNA of SOD1 and promotes its degradation to reduce mutant SOD1 protein level. Many other experimental drugs targeting different ALS disease genes are also undergoing clinical trials. Hopefully, in a near future, ALS patients with common disease-causing genes may benefit from such therapies.