Emerich Dwaine F, Thanos Christopher G
LCT BioPharma, Inc., Providence, RI, USA.
Curr Gene Ther. 2006 Feb;6(1):147-59. doi: 10.2174/156652306775515547.
Ciliary neurotrophic factor (CNTF) is a cytokine with neurotrophic activity across a broad spectrum of peripheral and central nervous system (CNS) cells. While its therapeutic potential for CNS diseases has been clear for sometime, the blood brain barrier (BBB) hinders the systemic delivery of CNTF and direct bolus injections are not suitable due to the short half-life of CNTF. One means of overcoming the BBB while providing continuous delivery of CNTF is with immunoisolated cellular implants that produce and deliver CNTF directly to the region of interest. Cells can be protected from host rejection by encapsulating, or surrounding, them within an immunoisolatory, semipermeable membrane that admits oxygen and required nutrients and releases bioactive cell secretions, but restricts passage of larger cytotoxic agents from the host immune defense system. The selective membrane eliminates the need for chronic immunosuppression of the host and allows the implanted cells to be obtained from nonhuman sources. In this review we discuss cell immunoisolation for Huntington's disease and retinitis pigmentosa. These two indications are highlighted because of extensive pre-clinical data supporting the general concept and recent clinical data that both strengthens the theoretical role of CNTF for treating neurodegeneration and justifies additional clinical evaluation in these and other diseases.
睫状神经营养因子（CNTF）是一种细胞因子，对广泛的外周和中枢神经系统（CNS）细胞具有神经营养活性。虽然其对中枢神经系统疾病的治疗潜力在一段时间以来已经很明确，但血脑屏障（BBB）阻碍了CNTF的全身递送，并且由于CNTF半衰期短，直接推注并不合适。一种克服血脑屏障同时持续递送CNTF的方法是使用免疫隔离细胞植入物，其可产生CNTF并将其直接递送至感兴趣的区域。通过将细胞封装或包裹在免疫隔离的半透膜内，可保护细胞免受宿主排斥，该半透膜允许氧气和所需营养物质进入，并释放生物活性细胞分泌物，但限制来自宿主免疫防御系统的较大细胞毒性剂的通过。这种选择性膜消除了对宿主进行长期免疫抑制的需要，并允许植入细胞来源于非人类。在本综述中，我们讨论了针对亨廷顿舞蹈病和色素性视网膜炎的细胞免疫隔离。突出这两种适应症是因为有大量临床前数据支持这一总体概念，以及最近的临床数据，这些数据既强化了CNTF治疗神经退行性变的理论作用，也证明了在这些疾病和其他疾病中进行额外临床评估的合理性。
