DEVELOPING A MICRORNA-TARGETED THERAPY FOR ALS

描述（由申请人提供）：肌萎缩性侧索硬化症的特征在于脊髓中运动神经元的进行性丧失，导致僵硬、严重虚弱、骨骼肌萎缩，并最终在3-5年内死于呼吸衰竭。目前没有显著减缓疾病进展的疗法。在动物模型和ALS患者的样本中，我们发现了称为microRNA的小非编码RNA的变化。我们现在将验证一种特定的microRNA作为治疗靶点，并开发一种使用反义寡核苷酸抑制这种microRNA的方法。我们假设在动物模型中抑制这种miRNA将显著减缓ALS。鉴于我们目前在ALS患者中使用反义寡核苷酸的I期试验的经验，我们打算将我们的研究结果转化为ALS的新疗法。

DESCRIPTION (provided by applicant): Amyotrophic lateral sclerosis is characterized by the progressive loss of motor neurons in the spinal cord, resulting in stiffness, severe weakness, atrophy of skeletal muscles, and eventual death from respiratory failure in 3-5 years. There are no current therapies that substantially slow the progression of the disease. In animal models and in samples from ALS patients, we have discovered changes in small non-coding RNA called microRNAs. We will now validate one particular microRNA as a therapeutic target and develop a method of inhibiting this microRNA using antisense oligonucleotides. We hypothesize that inhibition of this miRNA will substantially slow ALS in animal models. Given our current experience in Phase I trial using antisense oligonucleotides in ALS patients; we intend to translate our findings from this grant to a novel therapeutic for ALS.