• 来稿:陈琳   北京市虹天济神经科学研究院

  • Neurology. 2006 Jul 11;67(1):20-7.  Review.

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  • Neuroprotective agents for clinical  trials in ALS: a systematic assessment

  •  

  • Traynor BJ, Bruijn L, Conwit R, Beal F,  O'Neill G, Fagan SC, Cudkowicz ME.

  • Neurology Clinical Trials Unit, Department of Neurology,  Massachusetts  General Hospital,

  • Boston, USA. traynorb@mail.nih.gov

  •  

  • BACKGROUND: Riluzole is currently the  only Food and Drug Administration-approved treatment for ALS, but its effect on  survival is modest.

  • OBJECTIVE: To identify potential  neuroprotective agents for testing in phase III clinical trials and to outline  which data need to be collected for each  drug.

  • METHODS: The authors identified 113  compounds by inviting input from academic clinicians and researchers and via  literature review to identify agents that have been tested in ALS animal models  and in patients with ALS. The list was initially narrowed to 24 agents based on  an evaluation of scientific rationale, toxicity, and efficacy in previous animal  and human studies. These 24 drugs underwent more detailed pharmacologic  evaluation.

  • RESULTS: Twenty drugs were selected as  suitable for further development as treatments for patients with ALS. Talampanel  and tamoxifen have completed early phase II trials and have demonstrated  preliminary efficacy. Other agents (ceftriaxone, minocycline, ONO-2506, and  IGF-1 polypeptide) are already in phase III trials involving large numbers of  patients with ALS. Remaining agents (AEOL 10150, arimoclomol, celastrol,  coenzyme Q10, copaxone, IGF-1-viral delivery, memantine, NAALADase inhibitors,  nimesulide, scriptaid, sodium phenylbutyrate, thalidomide, trehalose) require  additional preclinical animal data, human toxicity and pharmacokinetic data  including CNS penetration prior to proceeding to large scale phase III human  testing. Further development of riluzole analogues should be considered.  

  • CONCLUSIONS: Several potential  neuroprotective compounds, representing a wide range of mechanisms, are  available and merit further investigation in ALS.

 

 

骨髓源性单核细胞促进脊髓损伤功能恢复的神经保护作用
嗅鞘细胞移植治疗脊髓损伤的动物实验和临床应用.PDF

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