CNS10-NPC-GDNF Delivered to the Motor Cortex for ALS
- Conditions
- Amyotrophic Lateral Sclerosis
- Interventions
- Biological: CNS10-NPC-GDNF
- Registration Number
- NCT05306457
- Lead Sponsor
- Cedars-Sinai Medical Center
- Brief Summary
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.
- Detailed Description
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
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 16
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description CNS10-NPC-GDNF - Group C CNS10-NPC-GDNF 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 CNS10-NPC-GDNF - Group A CNS10-NPC-GDNF 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 CNS10-NPC-GDNF - Group B CNS10-NPC-GDNF 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
- Primary Outcome Measures
Name Time Method Safety, as evaluated by the incidence of Adverse Events and Serious Adverse Events and their relationship to the treatment 12 months post-operatively Safety, as evaluated by changes from baseline in the brain MRI 12 months post-operatively
- Secondary Outcome Measures
Name Time Method Pinch Strength Pinch Strength testing will be performed 7 times over 15 months Change from baseline for pinch strength
Force Generation via Accurate Test of Limb Isometric Strength (ATLIS) testing ATLIS testing will be performed 7 times over 15 months Change from baseline for force generation by ATLIS
Functional Hand assessments using 9-hole peg test 9-hole peg testing will be performed 7 times over 15 months Change from baseline for 9-hole peg test
Penn Upper Motor Neuron Score (PUMNS) PUMNS will be performed 7 times over 15 months Change from baseline for Penn Upper Motor Neuron Score. (Scale of 0-32, where 0 is normal)
Hand/Wrist Strength Hand/Wrist strength testing will be performed 7 times over 15 months Change from baseline for Hand/Wrist strength using Hand-held dynamometer
Compound Motor Action Potential (CMAP) CMAP will be performed 7 times over 15 months Change from baseline for CMAP
Hand Knob - Functional MRI (fMRI) fMRI will be performed up to 4 times over 15 months Changes from baseline in brain activity in the hand knob area evaluated by fMRI
Trial Locations
- Locations (1)
Cedars-Sinai Medical Center
🇺🇸Los Angeles, California, United States