CNS10-NPC-GDNF for the Treatment of ALS

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)

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