The investigator is examining the safety of transplanting cells that have been engineered to produce a growth factor into the spinal cord 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 neuronal 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 neuronal cells. Therefore, the cells are called "CNS10-NPC-GDNF." The investigational treatment has been tested in animals, but it has not yet been tested in people. In this study, we want to learn if CNS10-NPC-GDNF cells are safe to transplant into the spinal cords of people.
This study will be the first to use a genetically modified progenitor cells to treat a neurodegenerative disease. This is a Phase 1/2a, single-center, blinded (as to side of injection), safety study of two escalating doses of human neural progenitor cells expressing GDNF (CNS10-NPC-GDNF) delivered unilaterally to the lumbar region in ALS subjects with moderate leg involvement. Subjects meeting all Eligibility Criteria and providing Informed Consent will be enrolled in one of two 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 two weeks between surgeries. Specific aims: Safety, as evaluated by: * Adverse Events and Serious Adverse Events * Clinical laboratory assessments, as clinically indicated (hematology, chemistry, immunology)
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
18
All patients will received unilateral lumbar spinal cord injections of CNS10-NPC-GDNF cells.
A newly developed stereotactic frame is being evaluated as a part of this trial
Cedars-Sinai Medical Center
Los Angeles, California, United States
Safety evaluated by Adverse Events and Serious Adverse Events, post-operative MRI, and clinical laboratory assessments
Safety, as evaluated by: * Adverse Events and Serious Adverse Events * Post-op MRI * Clinical laboratory assessments, as clinically indicated (hematology, chemistry, immunology)
Time frame: Patients will be followed postoperatively for 12 months
Compound Motor Action Potential (CMAP)
Compound Motor Action Potential - CMAP (Tibialis anterior)
Time frame: CMAP will be performed 7 times over 15 months
Force Generation via ATLIS testing
Lower extremity Force Generation via ATLIS testing
Time frame: ATLIS testing will be performed 7 times over 15 months
Quantitative Muscle MRI
Quantitative Muscle MRI of bilateral lower extremities
Time frame: Muscle MRI will be performed 6 times over 15 months
Electrical Impedance Myography (EIM)
Lower Extremity Electrical Impedance Myography (EIM)
Time frame: EIM will be performed 7 times over 15 months
Assessment of glial cell line derived neurotrophic factor (GDNF) in the cerebral spianl fluid (CSF)
Assessment of GDNF in the CSF
Time frame: CSF will be collected at 3 time points over 12 months
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.