Pascual-Gilabert Marta, Artero Ruben, López-Castel Arturo
Myogem Health Company, S.L, Barcelona, Spain.
University Institute for Biotechnology and Biomedicine (BIOTECMED), University of Valencia, Valencia, Spain; Translational Genomics Group, Incliva Biomedical Research Institute, Valencia, Spain.
Drug Discov Today. 2023 Mar;28(3):103489. doi: 10.1016/j.drudis.2023.103489. Epub 2023 Jan 9.
The beginning of the 20th decade has witnessed an increase in drug development programs for myotonic dystrophy type 1 (DM1). We have collected nearly 20 candidate drugs with accomplished preclinical and clinical phases, updating our previous drug development pipeline review with new entries and relevant milestones for pre-existing candidates. Three interventional first-in-human clinical trials got underway with distinct drug classes, namely AOC 1001 and DYNE-101 nucleic acid-based therapies, and the small molecule pitolisant, which joins the race toward market authorization with other repurposed drugs, including tideglusib, metformin, or mexiletine, already in clinical evaluation. Furthermore, newly disclosed promising preclinical data for several additional nucleic-acid therapeutic candidates and a CRISPR-based approach, as well as the advent into the pipeline of novel therapeutic programs, increase the plausibility of success in the demanding task of providing valid treatments to patients with DM1.
20世纪20年代初见证了针对1型强直性肌营养不良症（DM1）的药物研发项目有所增加。我们已收集了近20种完成了临床前和临床阶段的候选药物，用新的条目以及现有候选药物的相关里程碑更新了我们之前的药物研发流程综述。三项针对不同药物类别的首次人体干预性临床试验已经开展，即AOC 1001和DYNE - 101核酸疗法，以及小分子匹莫林，它与其他已在临床评估中的 repurposed 药物（包括替格列净、二甲双胍或美西律）一同角逐市场授权。此外，新披露的几种额外核酸治疗候选药物和一种基于CRISPR方法的有前景的临床前数据，以及新的治疗项目进入研发流程，增加了在为DM1患者提供有效治疗这一艰巨任务中取得成功的可能性。
