Unrelated Umbilical Cord Blood Transplantation for the Treatment of Amyotrophic Lateral Sclerosis (ALS)

A Single-Arm, Open-Label, Single-Center Clinical Study on Unrelated Umbilical Cord Blood Transplantation for the Treatment of Amyotrophic Lateral Sclerosis (ALS)

Amyotrophic Lateral Sclerosis (ALS) is a rapidly progressive and fatal neurodegenerative disorder. Its global prevalence is approximately 0.73-1.89 per 100,000 individuals. In China, there are about 200,000 ALS patients, with approximately 25,000 new cases diagnosed annually. Microglia, the resident immune cells of the central nervous system (CNS), rapidly transition from a resting state to a pro-inflammatory phenotype (M1) in ALS. This activation leads to the release of a large number of inflammatory factors (such as TNF-α, IL-1β, IL-6, NO, ROS) and chemokines (such as MCP-1/CCL2), and triggers the NLRP3 inflammasome. Furthermore, systemic immune dysregulation plays a significant role in the pathogenesis of ALS. ALS patients exhibit reduced numbers of regulatory T cells (Tregs), alterations of activated CD8+ T cell infiltrates, and a shift in the helper T cell (Th1/Th2) balance towards the pro-inflammatory Th1 phenotype. In recent years, therapeutic strategies targeting novel pathways such as neuroinflammation, immune dysregulation, and energy metabolism have emerged, including the infusion of Tregs, mesenchymal stem cells (MSCs), and neural stem cells. However, these approaches have still failed to halt disease progression [NCT05695521, NCT03280056, NCT06973629, NCT02290886]. Recent research suggests that hematopoietic stem cell transplantation (HSCT) may disrupt the activation cycle between astrocytes and microglia, alleviate chronic inflammatory states in the CNS, partially mitigate mitochondrial dysfunction, and thereby slow neurodegeneration. Unrelated umbilical cord blood transplantation offers advantages such as low HLA-matching requirements, a lower risk of graft-versus-host disease (GVHD), a potent graft-versus-leukemia (GVL) effect, and immediate availability. Investigators plan to conduct an exploratory clinical trial to evaluate the safety and efficacy of umbilical cord blood transplantation for ALS patients. The preliminary plan is to enroll 8 adult subjects. Following successful neutrophil engraftment (defined as an absolute neutrophil count ≥0.5×10⁹/L for three consecutive days) and confirmation of complete donor chimerism. The trial will focus on assessing transplantation-related complications and patient tolerance. A 3-month post-transplantation follow-up will be conducted for a comprehensive evaluation of safety and efficacy for ALS patients.

Study Overview

• Status: Enrolling by invitation
• Conditions: ALS (Amyotrophic Lateral Sclerosis)
• Intervention / Treatment: Procedure: Mobilization Regimen; Procedure: Conditioning Regimen; Procedure: GVHD Prophylaxis; Procedure: umbilical cord blood; Procedure: Rescue

Detailed Description

Please see the detailed description in following content

• Study Type: Interventional
• Enrollment (Estimated): 8
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Tianjin, China
    • Institute of Hematology & Blood Diseases Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients with a confirmed diagnosis of ALS, with an ALSFRS-R score ≥35 and a maximum vital capacity ≥65%
• Aged >35 years and <50 years, with no gender restrictions
• Karnofsky Performance Status (KPS) score ≥70, and Eastern Cooperative Oncology Group (ECOG) Performance Status ≤2
• Unrelated umbilical cord blood and the recipient demonstrate high-resolution HLA (-A, -B, Cw, DR, DQ) matching at ≥4/6, 5/8, or 7/10 loci, and the post-thaw CD34+ cell count in the cord blood unit is ≥1.2×10⁵/kg (recipient body weight)
• Willing and able to comply with the study procedures and conditions, demonstrating good compliance
• Willing to receive at least two years of treatment and follow-up, with detailed medical records maintained
• The patient and/or their legal guardian voluntarily participate in this clinical trial, sign the informed consent form, and are capable of completing all follow-up assessments as required by the protocol

Exclusion Criteria:

• Patients with positive results in the following etiological tests: Human Immunodeficiency Virus (HIV-1/2), Human Cytomegalovirus DNA (HCMV-DNA), Epstein-Barr Virus DNA (EBV-DNA), Hepatitis B (positive for Hepatitis B surface antigen (HBsAg) or Hepatitis B virus DNA (HBV-DNA)), Hepatitis C antibody (HCV-Ab), or Treponema pallidum antibody (TP-Ab)
• Clinically significant active bacterial, viral, fungal, or parasitic infections as judged by the investigator during screening
• Patients who have previously received gene therapy or allogeneic hematopoietic stem cell transplantation
• First-degree relatives with known or suspected familial cancer syndromes (including but not limited to hereditary breast and ovarian cancer syndrome, hereditary nonpolyposis colorectal cancer syndrome, familial adenomatous polyposis, etc.)
• Diagnosis of major psychiatric disorders or predisposition to such conditions that would significantly impair the ability to participate in the clinical study
• History of major organ impairment, including: Liver disorders: Liver function tests showing AST or ALT >3 × ULN; total serum bilirubin >2.5 × ULN; for cases consistent with Gilbert syndrome, total bilirubin >3 × ULN and direct bilirubin >2.5 × ULN; history of hepatic bridging fibrosis, cirrhosis, or active hepatitis; Cardiac disorders: Left ventricular ejection fraction (LVEF) <45% at screening; New York Heart Association (NYHA) Class III or IV congestive heart failure; severe arrhythmias requiring treatment; poorly controlled hypertension (systolic blood pressure >160 mmHg and/or diastolic blood pressure >100 mmHg despite antihypertensive therapy), or prior history of hypertensive emergencies, hypertensive encephalopathy, or unstable angina; history of myocardial infarction, coronary artery bypass graft surgery, peripheral arterial bypass graft implantation, or stent placement within 12 months prior to enrollment; clinically significant valvular disease; calculated eGFR <60 mL/min/1.73m²; Pulmonary function: FEV1/FVC <60% and/or diffusing capacity less than 60% of predicted; clinically significant evidence of pulmonary hypertension requiring medical intervention
• Uncorrectable coagulation dysfunction or history of severe bleeding disorders
• Any other condition deemed by the physician to render the subject unsuitable for hematopoietic stem cell transplantation
• Known hypersensitivity to the investigational drug or its components
• Participation in or ongoing participation in other interventional clinical studies within 3 months prior to screening
• Vaccination with live vaccines within 6 weeks prior to screening
• Pregnant or breastfeeding women
• History of solid organ transplantation
• Poor compliance of the subject with the study protocol
• Any other condition considered by the investigator as unsuitable for participation in this clinical trial
• Unwillingness of the subject to provide pre-existing valid diagnostic evidence before treatment or to undergo bone marrow, lumbar puncture, blood tests, and other examinations after treatment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: ALS group

Procedure: Mobilization Regimen; Mobilization and Collection of Recipient's Autologous Peripheral Blood Hematopoietic Stem Cells during the Screening Phase for Cryopreservation and Future Use: G-CSF at 5 µg/kg, administered subcutaneously every 12 hours (q12h). Collection begins when the white blood cell count exceeds 5×10⁹/L and the platelet count exceeds 50×10⁹/L. The collected cells are cryopreserved in liquid nitrogen.; Procedure: Conditioning Regimen; A reduced-intensity myeloablative conditioning regimen consisting of Fludarabine (Flu), Melphalan (Mel), Thiotepa (TT), and Total Marrow Irradiation (TMI) is employed.; Procedure: GVHD Prophylaxis; A combination of Cyclosporine A (CsA) and short-course Mycophenolate Mofetil (MMF) is used.; Procedure: umbilical cord blood; UCB Infusion: On transplant day 0, the thawed umbilical cord blood unit is infused. Dexamethasone 5 mg is administered intravenously 30 minutes prior to the infusion.; Procedure: Rescue; Rescue Protocol for Graft Failure: The cryopreserved autologous peripheral HSCs are reinfused to restore hematopoietic function.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	Survival status of ALS patients after umbilical cord blood transplantation	1 year, 3 year, 5 year
LVGI Safety Score	Considering the limited assessment conditions within the transplant isolation unit, this study has modified and simplified the ALSFRS-R scale and incorporated the Inbody score, which provides a comprehensive assessment of muscle mass and body fat mass, to form the "LVGI" safety score. Among the components, VCmax refers to maximum lung capacity; Grip quantifies upper limb strength using a dynamometer, with the Grip Strength-to-Body Weight Index calculated as Grip Strength (kg) / Body Weight (kg) × 100. The results of each assessment are compared. A change within ± 20% in the LSGI score within the first month post-transplantation compared to the pre-transplantation score is considered safe.	3 month, 6 month, 1 year
ALS related assessment	Assessment of Disease Functional Progression: The ALSFRS-R scale was used to conduct standardized assessments at baseline (1, 3, 6, 12, 18, and 24 months post-transplantation). Biomarker of Neuroaxonal Injury: Peripheral blood and CSF samples were collected from patients to assess neurofilament light chain (NFL). By analyzing changes in NFL relative to baseline, the dynamic changes in neuroaxonal injury following umbilical cord blood transplantation intervention were objectively evaluated. Imaging Evaluation: MR and PET-CT.	3 month, 6 month, 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of Drug-Induced Liver and Kidney Toxicity	Liver - RUCAM Score: <1: Excluded 1-2: Unlikely 3-5: Possible 6-8: Probable 8: Highly probable Kidney - KDIGO Score: Acute Kidney Injury (AKI) is defined by meeting any one of the following three criteria: ① Increase in serum creatinine (Scr) by ≥0.3 mg/dL (≥26.5 µmol/L) within 48 hours; ② Increase in Scr to >1.5 times the baseline value, which is known or presumed to have occurred within the prior 7 days; ③ Urine output <0.5 mL/(kg·h) for 6 hours.	up to 24 weeks
Assessment of acute GVHD	Primarily based on the modified Glucksberg criteria and the acute GVHD International Consortium (MAGIC) grading criteria.	up to 24 weeks

Collaborators and Investigators

• Sponsor: Institute of Hematology & Blood Diseases Hospital, China

Study record dates

Study Major Dates

• Study Start (Actual): December 29, 2025
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: February 9, 2026
• First Submitted That Met QC Criteria: April 13, 2026
• First Posted (Actual): April 20, 2026

Study Record Updates

• Last Update Posted (Actual): April 20, 2026
• Last Update Submitted That Met QC Criteria: April 13, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Neuromuscular Diseases; Metabolic Diseases; Neurodegenerative Diseases; Spinal Cord Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Motor Neuron Disease; Nutritional and Metabolic Diseases; Amyotrophic Lateral Sclerosis; Investigative Techniques; Therapeutics; Biological Therapy; Immunologic Techniques; Immunomodulation; Immunotherapy; Immunosuppression Therapy; Transplantation Conditioning
• Other Study ID Numbers: IIT2025142

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: No
• Studies a U.S. FDA-regulated device product: No