Human Neural Progenitor Cells Secreting Glial Cell Line-Derived Neurotrophic Factor (CNS10-NPC-GDNF) for the Treatment of Amyotrophic Lateral Sclerosis

Full Study Summary:

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)

• More Information

  Primary Outcome Measures: Safety evaluated by Adverse Events and Serious Adverse Events, post-operative MRI, and clinical laboratory assessments [ Time Frame: Patients will be followed postoperatively for 12 months ] [ Designated as safety issue: No ] Safety, as evaluated by: Adverse Events and Serious Adverse Events Post-op MRI Clinical laboratory assessments, as clinically indicated (hematology, chemistry, immunology) Secondary Outcome Measures: Compound Motor Action Potential (CMAP) [ Time Frame: CMAP will be performed 7 times over 15 months ] [ Designated as safety issue: No ] Compound Motor Action Potential - CMAP (Tibialis anterior) Force Generation via ATLIS testing [ Time Frame: ATLIS testing will be performed 7 times over 15 months ] [ Designated as safety issue: No ] Lower extremity Force Generation via ATLIS testing Quantitative Muscle MRI [ Time Frame: Muscle MRI will be performed 6 times over 15 months ] [ Designated as safety issue: No ] Quantitative Muscle MRI of bilateral lower extremities Electrical Impedance Myography (EIM) [ Time Frame: EIM will be performed 7 times over 15 months ] [ Designated as safety issue: No ] Lower Extremity Electrical Impedance Myography (EIM) Assessment of glial cell line derived neurotrophic factor (GDNF) in the cerebral spianl fluid (CSF) [ Time Frame: CSF will be collected at 3 time points over 12 months ] [ Designated as safety issue: No ] Assessment of GDNF in the CSF

• Eligibility Criteria

  Gender:

  Female, Male

  Minimum Age:

  18

  Maximum Age:

  N/A

  Min Vital Capacity (% predicted normal):

  60

  Time since Symptom Onset:

  Time since Diagnosis:

  Can participants use Riluzole?

  Yes

  
  

  Inclusion Criteria:

  Confirmed diagnosis of ALS (Lab-supported Probable, Probable or Definite EI Escorial Criteria)
  Duration of symptoms ≤ 36 months
  Progressive weakness in lower extremities, with EMG supported evidence of denervation in both lower extremities.
  Forced Vital Capacity >60% of predicted normal in supine.
  Male/Female; Age: 18 and older
  Able to provide Informed Consent
  Be geographically accessible to the study site and able to travel to study site for required visits
  Have caregiver to assist in the transportation and care required by participation in the study
  Not taking riluzole or on a stable dose for ≥ 30 days
  For women of child bearing capacity, negative pregnancy test prior to surgery
  Medically able to undergo thoracolumbar laminectomy or laminoplasty as determined by the site PI and Neurosurgeon
  Medically able to tolerate the immunosuppression regimen as determined by the site PI

  Exclusion Criteria:

  Using invasive ventilatory assistance
  Diagnosis of another active or unstable medical illness that may interfere with study participation at discretion of PI
  Presence of any of the following conditions:

  • Current drug or alcohol abuse
  • Any known immunodeficiency syndrome
  • Unstable medical condition
  • Unstable psychiatric illness including psychosis and untreated major depression within 90 days of screening

  Persons of child bearing capacity not willing to practice birth control
  Receiving any investigational device/biologic/drug in past 30 days or any previous exposure to stem cell therapy
  Any condition in the lower extremities which precludes serial strength testing
  Any condition that the Neurosurgeon feels may pose complications for the surgery
  Any condition or ALS disease phenotype that the site PI feels may interfere with participation in the study or in the interpretation of study endpoints

• Site Contact Information

  Cedars-Sinai Medical Center
  Peggy Allred / .(JavaScript must be enabled to view this email address) / 310-423-1791
  Los Angeles, California 90048
  United States