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.
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
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
16
Unilateral injections of CNS10-NPC-GDNF into the motor cortex
Cedars-Sinai Medical Center
Los Angeles, California, United States
Safety, as evaluated by the incidence of Adverse Events and Serious Adverse Events and their relationship to the treatment
Time frame: 12 months post-operatively
Safety, as evaluated by changes from baseline in the brain MRI
Time frame: 12 months post-operatively
Force Generation via Accurate Test of Limb Isometric Strength (ATLIS) testing
Change from baseline for force generation by ATLIS
Time frame: ATLIS testing will be performed 7 times over 15 months
Pinch Strength
Change from baseline for pinch strength
Time frame: Pinch Strength testing will be performed 7 times over 15 months
Hand/Wrist Strength
Change from baseline for Hand/Wrist strength using Hand-held dynamometer
Time frame: Hand/Wrist strength testing will be performed 7 times over 15 months
Compound Motor Action Potential (CMAP)
Change from baseline for CMAP
Time frame: CMAP will be performed 7 times over 15 months
Functional Hand assessments using 9-hole peg test
Change from baseline for 9-hole peg test
Time frame: 9-hole peg testing will be performed 7 times over 15 months
Penn Upper Motor Neuron Score (PUMNS)
Change from baseline for Penn Upper Motor Neuron Score. (Scale of 0-32, where 0 is normal)
Time frame: PUMNS will be performed 7 times over 15 months
Hand Knob - Functional MRI (fMRI)
Changes from baseline in brain activity in the hand knob area evaluated by fMRI
Time frame: fMRI will be performed up to 4 times over 15 months
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.