NCT03725670

Direct Lentiviral Injection Gene Therapy for MLD

Direct Lentiviral TYF-ARSA Injection Gene Therapy for Metachromatic Leukodystrophy (MLD)

• Status: Recruiting
• Phase: N/A
• Study type: Interventional
• Enrollment: 10 (estimated)
• Sponsor: Shenzhen Geno-Immune Medical Institute · Academic / Other
• Sex: All
• Age: 1 Month – 50 Years
• Healthy volunteers: Not accepted

Summary

This is a Phase I/II clinical trial of gene therapy for treating Metachromatic leukodystrophy (MLD) using a safety and efficacy improved self-inactivating lentiviral vector TYF-ARSA to functionally correct the genetic defect. The primary objectives are to evaluate the safety and efficacy of the direct gene transfer clinical protocol.

Detailed description

Metachromatic leukodystrophy (MLD) is a rare lysosomal storage disease. This disease is an inherited single gene autosomal recessive defect. MLD is caused by a mutation in the ARSA gene encoding arylsulfatase A which leads to a deficiency in sulfatide degradation, resulting in its accumulation in oligodendrocytes, Schwann cells and neurons. A critical level of sulfatide storage can trigger demyelination, the hallmark of MLD, which results in multiple neurological symptoms. MLD has different onset ages including late infancy (1-2 years), adolescence (4 years-before sexual maturity) and adulthood (after sexual maturity). MLD patients are normally rescued by hematopoietic stem cell transplantation (HSCT) from a matched healthy donor. However, HSCT must be performed at a very early stage of the disease thus restricting its therapeutic opportunies in MLD patients. This trial aims to treat MLD using a safety and efficacy improved self-inactivating lentiviral vector (LV) carrying a functional MLD gene to correct the genetic defect by intrathecal (IT) and intravenous (IV) injections to delivery the lentiviral vector carrying a normal ARSA gene to correct the genetic defect. The primary objectives are to evaluate the safety of the improved LV TYF-ARSA and the direct injection gene transfer clinical protocol, the efficacy of degradative metabolite in patients after treatment, vector integration profile, and finally the long-term correction of the related pathological symptoms.

Conditions

• Metachromatic Leukodystrophy (MLD)

Interventions

Type	Name	Description
GENETIC	Intrathecal and intravenous LV gene therapy	Direct IT and IV LV gene therapy to deliver high levels of LVs at 1-2×10\^9 transduction units/ml which carry a normal ARSA gene

Timeline

• Start date: 2025-05-31
• Primary completion: 2025-05-31
• Completion: 2030-12-31
• First posted: 2018-10-31
• Last updated: 2025-06-26

Locations

1 site across 1 country: China