Phase 1b Trial of stem cells in ALS

描述（由申请人提供）：本提案概述了将人脊髓源性干细胞（HSSC）注射到ALS患者颈髓中的1b期临床试验计划。这项试验是埃默里大学已经进行的一项试验的后续，在该试验中，12名ALS患者被注射了相同的HSSC到腰椎脊髓中。为了使这种治疗方法更接近临床试验，以确定是否能有效改善疾病，我们建议测试HSSC注射到颈脊髓中的安全性。颈脊髓中的运动神经元支配呼吸横膈膜，呼吸横膈膜的丧失通常是ALS患者死亡的原因。我们认为，保护这些神经元可能通过保护呼吸功能来延长生命。本安全性试验将采用渐进式剂量递增，以确定可用于进行II期和III期疗效试验的长期目标的最大耐受剂量。有两个具体目标。在目标1中，我们提出按顺序递增递送剂量，如由1）细胞/注射的数量，2）注射到脐带中的数量，和3）单侧或双侧注射所定义的。该剂量递增方案旨在安全有效地测试我们达到预定目标治疗剂量的能力，该剂量可用于 下一阶段的疗效测试本提案的目的2是检查几个探索性终点，这些终点可用于在未来的II期和III期试验中检测该疗法的疗效。这些包括呼吸功能，膈肌功能，肌肉力量和肌肉电特性（电阻抗肌描记术）的测量。这项1b期试验的成功完成将允许测试这种治疗ALS的高度创新方法。其影响将超出ALS患者，因为这项新试验将提供有关手术方法和安全性的数据，以及与脊髓损伤，多发性硬化，脊髓性肌萎缩以及其他神经系统疾病的细胞疗法高度相关的试验设计。

DESCRIPTION (provided by applicant): This proposal outlines a plan for a Phase 1b clinical trial for the injection of human spinal cord derived stem cells (HSSCs) into the cervical spinal cord of patients with ALS. This trial is a follow up to a trial already underway at Emory University, where 12 ALS patients have been injected with the same HSSCs into the lumbar spinal cord. In order to move this therapeutic approach closer to a clinical trial to determine if t is effective in ameliorating disease, we are proposing to test the safety of HSSC injection into the cervical spinal cord. Motor neurons in the cervical spinal cord innervate the respiratory diaphragm, the loss of which is typically the cause of death in ALS patients. We propose that the protection of these neurons is likely to prolong life by preserving respiratory function. This safety trial will employ progressive dose escalation to determine the maximum tolerated dose that can be used for the long term goal of performing Phase 2 and Phase 3 efficacy trials. There are two specific aims. In Aim 1 we propose to sequentially escalate the dose of delivery as defined by 1) the number of cells/injection, 2) the number of injections into the cord, and 3) either unilateral or bilateral injections. This dose escalation scheme is designed to safely and efficiently test our ability to achieve a pre-defined target therapeutic dose, which can be used in the next phase of testing therapeutic efficacy. Aim 2 of this proposal is to examine several exploratory endpoints that may be used to test the efficacy of this therapy in future Phase 2 and Phase 3 trials. These include measures of respiratory function, diaphragm function, muscle strength, and electrical characteristics of muscle (Electrical Impedance Myography). Successful completion of this Phase 1b trial will allow for testing of this highly innovative approach to the treatment of ALS. The impact will extend beyond patients with ALS since this novel trial will provide data on surgical approach and safety, as well as trial design that will be highly relevant to cellular therapeutics for spinal cord injury, multiple sclerosis, spinal muscular atrophies, as well as other neurological diseases.