cns10-npc-gdnf delivered to the motor cortex for als

Conditions: Amyotrophic Lateral Sclerosis

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.

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

Eligibility criteria:
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

Keywords: als stem cells growth factor regenerative neural progenitor cells npc transplantation