Specific and efficient gene transfer strategy offers new potentialities for the treatment of motor neurone diseases
Specific and efficient gene transfer strategy offers new potentialities for the treatment of motor neurone diseases
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DOI：
10.1097/00001756-199512290-00088
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发表时间：
1995-12-29
期刊：
影响因子：
1.7
通讯作者：
Mallet, J
中科院分区：
文献类型：
--
作者：
Finiels, F;Ribotta, MGY;Mallet, J
几种生长因子是治疗运动神经元疾病的候选因子。然而，没有有效、安全和可行的给药途径，这阻碍了这些潜在治疗剂的临床使用。我们表明，特异性和高产量的基因转移到运动神经元可以通过外周肌肉注射重组腺病毒。这些载体从肌肉运动单位逆行转运到运动神经元细胞体。因此，通过适当选择注射肌肉，基因转移可以特异性地靶向脊髓的特定区域。基因转移的效率很高，58-100%的运动神经元传入注射的肌肉表达转基因。这种新的治疗方案允许特异性靶向运动神经元而不损伤脊髓，并应避免与全身施用治疗因子相关的不良副作用。
SEVERAL growth factors are candidates for the therapy of motor neurone diseases. However, there is no efficient, safe, and practicable administration route which hampers the clinical use of these potentially therapeutic agents. We show that specific and high yield gene transfer into motor neurones can be obtained by peripheral intramuscular injections of recombinant adenoviruses. These vectors are retrogradely transported from muscular motor units to motor neurone cell bodies. Gene transfer can thus be specifically targeted to particular regions of the spinal cord by appropriate choice of the injected muscle. The efficiency of gene transfer is high, with 58-100% of the motor neurones afferent to the injected muscle expressing the transgene. This new therapeutic protocol allows specific targeting of motor neurones without lesioning the spinal cord, and should avoid undesirable side effects associated with systemic administration of therapeutic factors.