Vanoli Fiammetta, Rinchetti Paola, Porro Francesca, Parente Valeria, Corti Stefania
Dino Ferrari Centre, Neuroscience Section, Department of Pathophysiology and Transplantation (DEPT), University of Milan, Neurology Unit, IRCCS Foundation Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
J Cell Mol Med. 2015 Sep;19(9):2058-66. doi: 10.1111/jcmm.12606. Epub 2015 Jun 20.
Spinal muscular atrophy with respiratory distress (SMARD1) is an autosomal recessive neuromuscular disease caused by mutations in the IGHMBP2 gene, encoding the immunoglobulin μ-binding protein 2, leading to motor neuron degeneration. It is a rare and fatal disease with an early onset in infancy in the majority of the cases. The main clinical features are muscular atrophy and diaphragmatic palsy, which requires prompt and permanent supportive ventilation. The human disease is recapitulated in the neuromuscular degeneration (nmd) mouse. No effective treatment is available yet, but novel therapeutical approaches tested on the nmd mouse, such as the use of neurotrophic factors and stem cell therapy, have shown positive effects. Gene therapy demonstrated effectiveness in SMA, being now at the stage of clinical trial in patients and therefore representing a possible treatment for SMARD1 as well. The significant advancement in understanding of both SMARD1 clinical spectrum and molecular mechanisms makes ground for a rapid translation of pre-clinical therapeutic strategies in humans.
伴有呼吸窘迫的脊髓性肌萎缩症（SMARD1）是一种常染色体隐性神经肌肉疾病，由编码免疫球蛋白μ结合蛋白2的IGHMBP2基因突变引起，导致运动神经元退化。它是一种罕见的致命疾病，大多数病例在婴儿期早期发病。主要临床特征为肌肉萎缩和膈肌麻痹，这需要及时且持续的支持性通气。人类疾病在神经肌肉变性（nmd）小鼠中得以重现。目前尚无有效治疗方法，但在nmd小鼠上测试的新型治疗方法，如使用神经营养因子和干细胞疗法，已显示出积极效果。基因疗法在脊髓性肌萎缩症中已证明有效，目前正处于患者临床试验阶段，因此也可能是治疗SMARD1的一种方法。对SMARD1临床谱和分子机制认识的显著进展为临床前治疗策略在人类中的快速转化奠定了基础。
