Pantoja Mario, Ruohola-Baker Hannele
Department of Biochemistry; Institute for Stem Cell and Regenerative Medicine; University of Washington; Seattle, WA USA.
Rare Dis. 2013 May 10;1:e24995. doi: 10.4161/rdis.24995. eCollection 2013.
Progress into developing therapeutics for rare diseases can be accelerated for those diseases that can be modeled in genetically tractable organisms. Here we comment on one disease, Duchenne Muscular Dystrophy (DMD), modeled in Drosophila that brought together disparate lines of research toward the goal of developing a therapeutic. Though the bioactive lipid sphingosine 1-phosphate (S1P) has been implicated in many anabolic processes in many cell types and tissues, including muscle, this work confirmed the therapeutic potential of assessing this pathway for DMD. Genetic dissection of sphingolipid metabolism showed the suppression of muscle structural and functional defects in flies. Moreover, improvement of muscle defects using known pharmacological agents that raise S1P levels in vivo highlight the potential of Drosophila as a drug-screening tool for DMD. We and others have extended S1P studies into the mouse model of DMD and have shown a partial amelioration of symptoms associated with DMD. Translation of this work to mammals makes the sphingolipid metabolism pathway a promising target for further drug development that may benefit the human condition.
对于那些可以在基因易处理的生物体中建模的罕见疾病，开发治疗方法的进程可以加快。在此，我们评论一种在果蝇中建模的疾病——杜氏肌营养不良症（DMD），它将不同的研究方向汇聚在一起，朝着开发一种治疗方法的目标迈进。尽管生物活性脂质鞘氨醇 1 - 磷酸（S1P）已被证明在包括肌肉在内的许多细胞类型和组织的许多合成代谢过程中发挥作用，但这项研究证实了评估该通路对 DMD 的治疗潜力。鞘脂代谢的基因剖析显示果蝇肌肉结构和功能缺陷得到抑制。此外，使用已知的能在体内提高 S1P 水平的药物改善肌肉缺陷，凸显了果蝇作为 DMD 药物筛选工具的潜力。我们和其他人已将 S1P 研究扩展到 DMD 的小鼠模型，并显示出与 DMD 相关症状的部分改善。这项研究成果向哺乳动物的转化使得鞘脂代谢途径成为进一步药物开发的一个有前景的靶点，可能造福人类。
