Wellcome  Institute of Neuroscience, Soochow University ID:游客 [登陆]

Professor Hua Yimin made a breakthrough in the study of spinal muscular atrophy

来源:本站作者:刘晓红发布于:2015-01-16 人阅读

    Professor Hua Yimin at Institute of Neuroscience, Soochow University made a breakthrough in understanding the pathogenesis of spinal muscular atrophy. The work was published online this month ina famous biomedical journal Genes & Development. The article is entitled “Motor neuron cell-nonautonomous rescue of spinal muscular atrophy phenotypes in mild and severe transgenic mouse models” with Professor Hua being the first authorand a co-corresponding author.








    Spinal muscular atrophy (SMA) is an autosomal recessive disease, the number one genetic killer of young children. In SMA patients, the survival of motor neuron 1 (SMN1) gene is mutated, resulting in reduced expression of the SMN protein that in turn causes degeneration of spinal-cord motor neurons and subsequent muscle denervation and atrophy. There is currently no available cure for SMA.


    Previously, Professor Hua Yimin, in collaboration with Professor Krainer at Cold Spring Harbor Laboratory and ISIS Pharmaceuticals, developed an antisense drug (ASO10-27 or ISIS-SMNRx) to treat SMA; ASO10-27 activates a backup defective gene called SMN2 and restores cellular SMN levels. This drug is now in Phase III Clinical Trials in the USA and Canada. In the new study, Professor Hua and his collaborators elegantly designed a “decoy” sense oligonucleotide with perfect base-pairing to ASO10-27. As ASO10-27 was subcutaneously (SC) delivered to a severe SMA mouse model, the decoy was injected into a lateral ventricle and neutralized the effect of the ASO in the CNS. Thus, SMN levels were only increased in peripheral tissues. Amazingly, this motor neuron cell-nonautonomous treatment route extended the lifespan of SMA mice to >20 fold, with significant improvements in vulnerable tissues and motor function. This observation demonstrates that peripheral SMN restoration compensates for its deficiency in the CNS and preserves motor neurons. This is a breakthrough discovery as it is a consensus view that increase of SMN in spinal-cord motor neurons is at least necessary, if not sufficient, to rescue SMA. This work is of great importance in understanding the molecular pathogenesis of SMA and optimizing its treatment strategies. The paper can be obtained online at: http://genesdev.cshlp.org.