Human Neural Progenitor Cells Secreting Glial Cell Line-Derived Neurotrophic Factor (CNS10-NPC-GDNF) Delivered to the Motor Cortex for the Treatment of Amyotrophic Lateral Sclerosis
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 16
- 试验地点
- 1
- 主要终点
- Safety, as evaluated by the incidence of Adverse Events and Serious Adverse Events and their relationship to the treatment
研究概览
简要总结
The investigator is examining the safety of transplanting cells, that have been engineered to produce a growth factor, into the motor cortex (brain) of patients with Amyotrophic Lateral Sclerosis (ALS). The cells are called neural progenitor cells, which are a type of stem cell that can become several different types of cells in the nervous system. These cells have been derived to specifically become astrocytes, which is a type of neural cell. The growth factor is called glial cell line-derived neurotrophic factor, or GDNF. GDNF is a protein that promotes the survival of many types of neural cells. Therefore, the cells are called "CNS10-NPC-GDNF." The investigational treatment has been tested in people by delivering it to the spinal cord. However, it has only been delivered to the motor cortex of animals. In this study, we want to learn if CNS10-NPC-GDNF cells are safe to transplant into the motor cortex (brain) of people.
详细描述
This study will be the first to use a genetically modified progenitor cell line delivered to the motor cortex to treat a neurodegenerative disease. This is a Phase 1/2a, single-center, safety study of two escalating doses of human neural progenitor cells expressing GDNF (CNS10-NPC-GDNF) delivered unilaterally to the "hand-knob" area of the motor cortex of patients with ALS.
Subjects meeting all Eligibility Criteria and providing Informed Consent will be enrolled in one of three sequential dosing groups. Subjects will be treated sequentially with a minimum of one month interval between surgeries for the first three subjects in each dosing cohort. The remaining subjects in the cohort will be treated with a minimum interval of at least one week between surgeries.
Primary Outcome:
Safety, as evaluated by:
- Adverse Events and Serious Adverse Events
- Post-op MRI and/or CT (with contrast) and as clinically indicated
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
CNS10-NPC-GDNF - Group A
Unilateral, Motor Cortex, 0.25x10^6 cells in 10 µL/site, 21 sites (5.25x10^6 total cells) - Motor cortex corresponding to the non-dominant hand
干预措施: CNS10-NPC-GDNF (Biological)
CNS10-NPC-GDNF - Group B
Unilateral, Motor Cortex, 0.5x10^6 cells in 10 µL/site, 21 sites (10.5x10^6 total cells) - Motor cortex corresponding to the non-dominant hand
干预措施: CNS10-NPC-GDNF (Biological)
CNS10-NPC-GDNF - Group C
Unilateral Motor Cortex, 0.5x10^6 cells in 10 µL/site, 21 sites (10.5x10^6 total cells) - Motor cortex corresponding to the dominant hand
干预措施: CNS10-NPC-GDNF (Biological)
结局指标
主要结局
Safety, as evaluated by the incidence of Adverse Events and Serious Adverse Events and their relationship to the treatment
时间窗: 12 months post-operatively
Safety, as evaluated by changes from baseline in the brain MRI
时间窗: 12 months post-operatively
次要结局
- Pinch Strength(Pinch Strength testing will be performed 7 times over 15 months)
- Force Generation via Accurate Test of Limb Isometric Strength (ATLIS) testing(ATLIS testing will be performed 7 times over 15 months)
- Functional Hand assessments using 9-hole peg test(9-hole peg testing will be performed 7 times over 15 months)
- Penn Upper Motor Neuron Score (PUMNS)(PUMNS will be performed 7 times over 15 months)
- Hand/Wrist Strength(Hand/Wrist strength testing will be performed 7 times over 15 months)
- Compound Motor Action Potential (CMAP)(CMAP will be performed 7 times over 15 months)
- Hand Knob - Functional MRI (fMRI)(fMRI will be performed up to 4 times over 15 months)
研究者
Clive Svendsen
Executive Director, Board of Governors Regenerative Medicine Institute
Cedars-Sinai Medical Center