Zanoteli Edmar, Maximino Jessica Ruivo, Conti Reed Umbertina, Chadi Gerson
Department of Neurology, Medical School of the University of São Paulo, Brazil.
Funct Neurol. 2010 Apr-Jun;25(2):73-9.
Spinal muscular atrophy (SMA) is an autosomal recessive disease characterized by degeneration and loss of lower motor neurons in the spinal cord and brainstem. Clinically, SMA has been classified into four types, according to the maximum function attained. The disease is caused by deletion or mutation of the telomeric copy of the SMN gene (SMN1), and the clinical severity is in part determined by the copy number of the centromeric SMN gene (SMN2). The SMN2 mRNA lacks exon 7, resulting in reduced production of the full-length SMN protein. Treatment of SMA consists of supportive care, although many drugs have been demonstrated to improve muscle strength and motor function of patients. The development of animal models of SMA has led to better interpretation of the physiopathology of the disease and testing of potential drug targets. Several mechanisms have been targeted in SMA drug trials, including neuroprotection, neurogenesis, energy metabolism improvement, anabolic stimulation and increment of SMN2 transcripts. Gene therapy and cell transplantation have also been tested in murine SMA.
脊髓性肌萎缩症（SMA）是一种常染色体隐性疾病，其特征为脊髓和脑干中的下运动神经元发生退化和丧失。临床上，根据所能达到的最大功能，SMA已被分为四种类型。该疾病由SMN基因（SMN1）端粒拷贝的缺失或突变引起，临床严重程度部分由着丝粒SMN基因（SMN2）的拷贝数决定。SMN2信使核糖核酸（mRNA）缺少外显子7，导致全长SMN蛋白的产生减少。SMA的治疗包括支持性护理，尽管许多药物已被证明可改善患者的肌肉力量和运动功能。SMA动物模型的开发有助于更好地解释该疾病的生理病理学，并对潜在的药物靶点进行测试。在SMA药物试验中，有几种机制成为了靶点，包括神经保护、神经发生、能量代谢改善、合成代谢刺激以及SMN2转录本的增加。基因治疗和细胞移植也已在小鼠SMA模型中进行了测试。
