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

Summary

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.

Conditions

• ALS (Amyotrophic Lateral Sclerosis)

Interventions

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.

Sponsors & Collaborators

• Institute of Hematology & Blood Diseases Hospital, China

  lead OTHER

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

35 Years

Max Age

50 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2025-12-29

Primary Completion

2027-12-31

Completion

2027-12-31

Countries

• China

Study Locations