McBenedict Billy, Hauwanga Wilhelmina N, Nezam Uzma, Ko Oo Aung, Eapi Srilatha, Pradhan Swetapadma, Dang Ngoc B, Cher Phoh Wen, Orsini Marco A, Lima Pessôa Bruno
Neurosurgery, Fluminense Federal University, Niterói, BRA.
Cardiology, Gaffrée and Guinle University Hospital, Federal University of the State of Rio de Janeiro, Rio de Janeiro, BRA.
Cureus. 2025 Jan 1;17(1):e76717. doi: 10.7759/cureus.76717. eCollection 2025 Jan.
Amyotrophic lateral sclerosis type 8 (ALS8) is a rare familial subtype of ALS caused by mutations in the vesicle-associated membrane protein-associated protein B (VAPB) gene, particularly the p.P56S mutation. It is distinguished by slower disease progression and an earlier onset compared to sporadic ALS forms, along with unique clinical features such as severe cramping, fasciculations, postural tremors, and cognitive and behavioral impairments. Although current pharmacological options, such as riluzole, edaravone, and sodium phenylbutyrate/taurursodiol, provide modest benefits, they fail to address the underlying genetic mechanisms of ALS8. Emerging gene therapies, RNA-based interventions, and stem cell approaches hold promise for precision-targeted treatments but face challenges in clinical application. Symptom management strategies, including respiratory, nutritional, and psychological support, are crucial for improving patient outcomes and quality of life. Despite significant progress in understanding the genetic and molecular pathogenesis of ALS8, its rarity, phenotypic variability, and limited clinical data pose challenges to therapeutic advancements. This narrative review highlights current therapeutic strategies, the unique clinical trajectory of ALS8, and potential pathways for innovative, subtype-specific interventions, emphasizing the need for multidisciplinary and targeted approaches to optimize care for this distinct ALS subtype.
8型肌萎缩侧索硬化症（ALS8）是一种罕见的家族性ALS亚型，由囊泡相关膜蛋白相关蛋白B（VAPB）基因的突变引起，尤其是p.P56S突变。与散发性ALS形式相比，它的疾病进展较慢且发病较早，并具有独特的临床特征，如严重痉挛、肌束震颤、姿势性震颤以及认知和行为障碍。尽管目前的药物治疗选择，如利鲁唑、依达拉奉和苯基丁酸钠/牛磺熊去氧胆酸，能带来一定益处，但它们无法解决ALS8的潜在遗传机制。新兴的基因疗法、基于RNA的干预措施和干细胞方法有望实现精准靶向治疗，但在临床应用中面临挑战。症状管理策略，包括呼吸、营养和心理支持，对于改善患者预后和生活质量至关重要。尽管在理解ALS8的遗传和分子发病机制方面取得了重大进展，但其罕见性、表型变异性和有限的临床数据对治疗进展构成了挑战。这篇叙述性综述强调了当前的治疗策略、ALS8独特的临床病程以及创新的、亚型特异性干预措施的潜在途径，强调需要采取多学科和靶向方法来优化对这种独特的ALS亚型的护理。
