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

NCT05306457 | Active Not Recruiting Phase 1 FDA Drug

• 1 other identifier: STUDY00000278
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Amyotrophic Lateral Sclerosis

Keywords

ALS; Stem cells; Growth Factor; Regenerative; Neural Progenitor Cells; NPC; Transplantation

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (7)

• Force Generation via Accurate Test of Limb Isometric Strength (ATLIS) testing

  ATLIS testing will be performed 7 times over 15 months

• Pinch Strength

  Pinch Strength testing will be performed 7 times over 15 months

• Hand/Wrist Strength

  Hand/Wrist strength testing will be performed 7 times over 15 months

• Compound Motor Action Potential (CMAP)

  CMAP will be performed 7 times over 15 months

• Functional Hand assessments using 9-hole peg test

  9-hole peg testing will be performed 7 times over 15 months

Study Arms (3)

CNS10-NPC-GDNF - Group A

EXPERIMENTAL

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

CNS10-NPC-GDNF - Group B

EXPERIMENTAL

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

CNS10-NPC-GDNF - Group C

EXPERIMENTAL

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

Interventions

CNS10-NPC-GDNF BIOLOGICAL

Unilateral injections of CNS10-NPC-GDNF into the motor cortex

CNS10-NPC-GDNF - Group A; CNS10-NPC-GDNF - Group B; CNS10-NPC-GDNF - Group C

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Confirmed diagnosis of ALS (Possible, Lab-supported Probable, Probable or Definite El Escorial Criteria)
• Duration of ALS symptoms ≤ 36 months
• Progressive weakness in upper extremities, with EMG supported evidence of denervation in both upper extremities
• Forced Vital Capacity ≥50% of predicted normal in supine
• Age: 18 years or 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 and/or edaravone or on a stable dose for ≥ 30 day
• For women of child bearing capacity, negative pregnancy test prior to surgery and willingness to use birth control for the duration of the trial.
• Medically able to undergo craniotomy as determined by the site PI and/or investigators
• Medically able to tolerate the immunosuppression regimen as determined by the site PI

You may not qualify if:

• 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 the past 30 days or any previous exposure to stem cell therapy
• Any condition in the upper extremities that precludes serial strength or coordination testing
• Any condition that the investigators feel 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
• Allergy to Beta-Lactam antibiotics
• Donor Specific Antibodies (DSA) ≥ 2500MFI or CPRA ≥ 20%
• Contraindications to MRI

Sponsors & Collaborators

• Cedars-Sinai Medical Center: lead
• California Institute for Regenerative Medicine (CIRM): collaborator

Study Sites (1)

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Motor Neuron Disease; Neurodegenerative Diseases; TDP-43 Proteinopathies; Neuromuscular Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Richard Lewis, MD

  Cedars-Sinai Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Executive Director, Board of Governors Regenerative Medicine Institute

Study Record Dates

• First Submitted: December 21, 2021
• First Posted: April 1, 2022
• Study Start: May 8, 2022
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): October 1, 2026
• Last Updated: August 19, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)