CNS10-NPC-GDNF Delivered to the Motor Cortex for ALS

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Amyotrophic Lateral Sclerosis
• Intervention / Treatment: Biological: CNS10-NPC-GDNF

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

• Study Type: Interventional
• Enrollment (Estimated): 16
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90048
      • Cedars-Sinai Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion:

1. Confirmed diagnosis of ALS (Possible, Lab-supported Probable, Probable or Definite El Escorial Criteria)
2. Duration of ALS symptoms ≤ 36 months
3. Progressive weakness in upper extremities, with EMG supported evidence of denervation in both upper extremities
4. Forced Vital Capacity ≥50% of predicted normal in supine
5. Age: 18 years or older
6. Able to provide Informed Consent
7. Be geographically accessible to the study site and able to travel to study site for required visits
8. Have caregiver to assist in the transportation and care required by participation in the study
9. Not taking riluzole and/or edaravone or on a stable dose for ≥ 30 day
10. For women of child bearing capacity, negative pregnancy test prior to surgery and willingness to use birth control for the duration of the trial.
11. Medically able to undergo craniotomy as determined by the site PI and/or investigators
12. Medically able to tolerate the immunosuppression regimen as determined by the site PI

Exclusion:

1. Using invasive ventilatory assistance
2. Diagnosis of another active or unstable medical illness that may interfere with study participation at discretion of PI

3. Presence of any of the following conditions:

   1. Current drug or alcohol abuse
   2. Any known immunodeficiency syndrome
   3. Unstable medical condition
   4. Unstable psychiatric illness including psychosis and untreated major depression within 90 days of screening
4. Persons of child bearing capacity not willing to practice birth control
5. Receiving any investigational device/biologic/drug in the past 30 days or any previous exposure to stem cell therapy
6. Any condition in the upper extremities that precludes serial strength or coordination testing
7. Any condition that the investigators feel may pose complications for the surgery
8. 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
9. Allergy to Beta-Lactam antibiotics
10. Donor Specific Antibodies (DSA) ≥ 2500MFI or CPRA ≥ 20%
11. Contraindications to MRI

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CNS10-NPC-GDNF - Group A; 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	Biological: CNS10-NPC-GDNF; Unilateral injections of CNS10-NPC-GDNF into the motor cortex
Experimental: CNS10-NPC-GDNF - Group B; 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	Biological: CNS10-NPC-GDNF; Unilateral injections of CNS10-NPC-GDNF into the motor cortex
Experimental: CNS10-NPC-GDNF - Group C; 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	Biological: CNS10-NPC-GDNF; Unilateral injections of CNS10-NPC-GDNF into the motor cortex

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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

Outcome Measure	Measure Description	Time Frame
Force Generation via Accurate Test of Limb Isometric Strength (ATLIS) testing	Change from baseline for force generation by ATLIS	ATLIS testing will be performed 7 times over 15 months
Pinch Strength	Change from baseline for pinch strength	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	Hand/Wrist strength testing will be performed 7 times over 15 months
Compound Motor Action Potential (CMAP)	Change from baseline for CMAP	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	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)	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	fMRI will be performed up to 4 times over 15 months

Collaborators and Investigators

• Sponsor: Cedars-Sinai Medical Center
• Collaborators: California Institute for Regenerative Medicine (CIRM)
• Investigators: Principal Investigator: Richard Lewis, MD, Cedars-Sinai Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): May 8, 2022
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): October 1, 2026

Study Registration Dates

• First Submitted: December 21, 2021
• First Submitted That Met QC Criteria: March 23, 2022
• First Posted (Actual): April 1, 2022

Study Record Updates

• Last Update Posted (Actual): August 19, 2025
• Last Update Submitted That Met QC Criteria: August 14, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: ALS; Stem cells; Transplantation; NPC; Growth Factor; Regenerative; Neural Progenitor Cells
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Pathologic Processes; Neuromuscular Diseases; Metabolic Diseases; Neurodegenerative Diseases; Spinal Cord Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Sclerosis; Motor Neuron Disease; Amyotrophic Lateral Sclerosis
• Other Study ID Numbers: STUDY00000278

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No