中国神经再生研究(英文版) ›› 2015, Vol. 10 ›› Issue (10): 1586-1588.doi: 10.4103/1673-5374.167783

• 观点:退行性病与再生 • 上一篇    下一篇

基因疗法治疗帕金森病:由志愿受试者捐助支持的10年进展

  

  • 收稿日期:2015-08-10 出版日期:2015-10-28 发布日期:2015-10-28

Gene therapy for Parkinson’s disease: a decade of progress supported by posthumous contributions from volunteer subjects

Raymond T. Bartus *   

  1. RTBioconsultants, Inc., San Diego, CA, USA; formerly, EVP and CSO, Ceregene, Inc., San Diego, CA, USA
  • Received:2015-08-10 Online:2015-10-28 Published:2015-10-28
  • Contact: Raymond T. Bartus, Ph.D.,Bartus@RTBioconsultants.com.
  • Supported by:

    The author acknowledges with sincere appreciation the collaborative contributions and past input from several key colleagues, including Tiffany Baumann and Chris Herzog who provided substantial support and assistance with clinical/regulatory activities and preclinical activities, respectively. Also, the collaborative work performed, and insight shared regarding analysis of autopsy tissue by Jeffrey Kordower is greatly appreciated, as are past suggestions and advice from Eugene Johnson, Warren Olanow and Anthony Lang.

摘要:

在过去的10年中,共有9项单独的基因治疗晚期帕金森病临床试验启动并完成,涉及大约150名帕金森病志愿患者。科学家们在规划和执行这些临床试验上花费了难以估量的时间,总体耗资高达数亿美元,最后试验完成了,但这些试验已经得到了什么呢?目前针对帕金森病治疗的努力效果都称不上十分显著。在过去的10年,基因治疗,使病毒载体安全传送至严重或慢性神经退行性疾病患者大脑。在整个20世纪90年代,以及21世纪的第一个10年,基因治疗的安全性,尤其是对中枢神经系统而言仍是需要解决的首要问题。虽然这是监管机构、投资者和众多利益相关者的一个主要障碍,但在这9例帕金森病基因治疗临床试验结果中已经取得了安全性结论。而这些临床观察的安全数据绝大多数基本上没有不良事件,尸体脑解剖数据,尽管样本量较小,但其报道仍是为这一结论提供了唯一确凿的支持。

Abstract:

Over the past decade, nine separate gene therapy clinical trials for advanced Parkinson’s disease (PD) have been launched and completed, involving the dosing of nearly 12-dozen PD volunteers who incurred significant risks to hopefully reduce symptoms and gain a better life. Each attempted to directly or indirectly correct or compensate for the dysfunction and death of dopamine neurons that originate in the substantia nigra (located in the brain stem), projecting their axon terminals to the putamen (centrally located within each cerebrum). All told, incalculable hours were spent planning and executing these clinical trials, collectively costing hundreds of millions of dollars. After all is said and done- what has been gained? It would be understandable if one answered that question by pointing out that treatments for PD have not improved following these efforts, for advanced patients are left with the same choices- and the same disappointing prognosis- faced a decade ago. However, as with any nascent and highly complicated endeavor, especially one also applying highly innovative and unproven technology, initial progress is often better measured by how much new information has been gained to guide further efforts, rather than how closely the ultimate goals may have been met.