Direct Lentiviral Injection Gene Therapy for MLD

August 27, 2026 updated by: Shenzhen Geno-Immune Medical Institute

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

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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

Important Regulatory Notice:

This trial record is only for global academic information registration on ClinicalTrials.gov. Neither the sponsor Beijing Meikang Jimian Biotechnology Co., Ltd. nor collaborator Shenzhen Geno-Immune Medical Institute has obtained NMPA clinical trial approval or clinical technology filing permission to carry out interventional cell therapy trials in mainland China.

ClinicalTrials.gov registration alone does not represent legal approval by Chinese health and drug regulatory authorities.

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.

Study Type

Interventional

Enrollment (Estimated)

10

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Lung-Ji Chang, Ph.D
  • Phone Number: +86 0755-86573763
  • Email: c@szgimi.org

Study Locations

  • China
    • Guangdong
      • Shenzhen, Guangdong, China, 518000
        • Lung-Ji Chang
        • Contact:
          • Lung-Ji Chang, Ph.D
          • Phone Number: +86 0755-86573763
          • Email: c@szgimi.org

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

3 years and older (Child, Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. MLD patient age >= 1 month
  2. ARSA gene sequence analysis to confirm MLD mutations
  3. Scoring system for brain MR Imaging confirmed MLD
  4. Parent / guardian / patient signing informed consent
  5. Patients and their families have a strong willingness to participate in clinical trials, and are willing to bear all the consequences caused by the failure of the trial, and sign an informed consent form

Exclusion Criteria:

  1. HIV positive patients
  2. Patients who are experiencing uncontrolled viral, bacterial or fungal infections, malignant tumors, heart abnormalities, liver dysfunction, or renal insufficiency
  3. Cannot perform an MRI
  4. Infection or dermatosis at pre-injection site
  5. Any condition that may increase the subjects' risk or interfere with the results of the trial. In addition to MLD, there are other neurological disorders.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Lentivirus-mediated delivery of ARSA to the CNS and the body
Intrathecal and intravenous injections with lentiviral TYF-ARSA vector carrying the functional gene
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Safety of IT and IV injections of lentiviral TYF-ARSA
Time Frame: up to 1 year follow up
Safety of IT and IV injections of lentiviral TYF-ARSA, determined by number of participants with treatment-related adverse events (AEs), according to scheduled assessments, vital signs, & physical examinations as assessed by CTCAE v4.0. AEs & clinically significant abnormalities (meeting grade 3, 4, or 5 criteria according to CTCAE) will be summarized by maximum intensity & relationship to the study drug(s). The grade of AEs will be summarized if related to the treatment.
up to 1 year follow up
Altered disease progression
Time Frame: up to 3 year follow up after treatment
Altered disease progression based on biochemical analysis.
up to 3 year follow up after treatment
Altered disease progression
Time Frame: up to 3 year follow up after treatment
Altered disease progression based on MRI brain imaging analysis
up to 3 year follow up after treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Shenzhen Geno-Immune Medical Institute

Investigators

  • Principal Investigator: Lung-Ji Chang, Ph.D, Shenzhen Geno-immune Medical Institute

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

May 31, 2027

Primary Completion (Estimated)

June 1, 2028

Study Completion (Estimated)

December 31, 2028

Study Registration Dates

First Submitted

September 25, 2018

First Submitted That Met QC Criteria

October 29, 2018

First Posted (Actual)

October 31, 2018

Study Record Updates

Last Update Posted (Actual)

September 1, 2026

Last Update Submitted That Met QC Criteria

August 27, 2026

Last Verified

August 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GIMI-IRB-18005

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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