Tuffaha Sami H, Singh Prateush, Budihardjo Joshua D, Means Kenneth R, Higgins James P, Shores Jaimie T, Salvatori Roberto, Höke Ahmet, Lee W P Andrew, Brandacher Gerald
a Department of Plastic and Reconstructive Surgery , Johns Hopkins University School of Medicine , Baltimore , MD , USA.
b The Curtis National Hand Center , Baltimore , MD , USA.
Expert Opin Ther Targets. 2016 Oct;20(10):1259-65. doi: 10.1080/14728222.2016.1188079. Epub 2016 May 24.
Peripheral nerve injuries often result in debilitating motor and sensory deficits. There are currently no therapeutic agents that are clinically available to enhance the regenerative process. Following surgical repair, axons often must regenerate long distances to reach and reinnervate distal targets. Progressive atrophy of denervated muscle and Schwann cells (SCs) prior to reinnervation contributes to poor outcomes. Growth hormone (GH)-based therapies have the potential to accelerate axonal regeneration while at the same time limiting atrophy of muscle and the distal regenerative pathway prior to reinnervation.
In this review, we discuss the potential mechanisms by which GH-based therapies act on the multiple tissue types involved in peripheral nerve regeneration to ultimately enhance outcomes, and review the pertinent mechanistic and translational studies that have been performed. We also address potential secondary benefits of GH-based therapies pertaining to improved bone, tendon and wound healing in the setting of peripheral nerve injury.
GH-based therapies carry great promise for the treatment of peripheral nerve injuries, given the multi-modal mechanism of action not seen with other experimental therapies. A number of FDA-approved drugs that augment the GH axis are currently available, which may facilitate clinical translation.
周围神经损伤常导致使人衰弱的运动和感觉功能障碍。目前尚无临床上可用于促进再生过程的治疗药物。手术修复后,轴突通常必须远距离再生才能到达并重新支配远端靶点。在重新支配之前,失神经支配的肌肉和施万细胞(SCs)的进行性萎缩导致预后不良。基于生长激素(GH)的疗法有可能加速轴突再生,同时在重新支配之前限制肌肉和远端再生途径的萎缩。
在本综述中,我们讨论基于GH的疗法作用于周围神经再生所涉及的多种组织类型以最终改善预后的潜在机制,并回顾已进行的相关机制和转化研究。我们还探讨了基于GH的疗法在周围神经损伤情况下对改善骨骼、肌腱和伤口愈合的潜在次要益处。
鉴于基于GH的疗法具有其他实验性疗法所没有的多模式作用机制,其在治疗周围神经损伤方面具有很大前景。目前有多种美国食品药品监督管理局(FDA)批准的增强GH轴的药物,这可能有助于临床转化。