Direct lentiviral gene therapy for metachromatic leukodystrophy
Direct Lentiviral TYF-ARSA Injection Gene Therapy for Metachromatic Leukodystrophy (MLD)
Testing a lentiviral gene therapy given into the spine and bloodstream to try to restore ARSA enzyme function in people with metachromatic leukodystrophy (MLD).
Quick facts
| Phase | Not applicable |
|---|---|
| Study type | Interventional |
| Enrollment | 10 (estimated) |
| Ages | 1 Month to 50 Years |
| Sex | All |
| Sponsor | Shenzhen Geno-Immune Medical Institute Academic / other |
| Locations | 1 site (Shenzhen, Guangdong) |
| Trial ID | NCT03725670 on ClinicalTrials.gov |
What this trial studies
This Phase I/II trial uses a self-inactivating lentiviral vector called TYF-ARSA to deliver a working ARSA gene directly to the central nervous system and systemically via intrathecal and intravenous injections. The trial enrolls genetically confirmed MLD patients (age ≥1 month) and follows them for safety, vector integration, biochemical markers of sulfatide degradation, and neurological outcomes. Primary goals are to determine whether the direct gene transfer is safe and can reduce pathogenic metabolite accumulation, while secondary analyses will examine vector integration profiles and long-term symptom change. The approach delivers the vector directly to patients rather than using ex vivo hematopoietic stem cell modification.
Who should consider this trial
Good fit: Ideal candidates are people of any onset age with genetically confirmed ARSA mutations and MRI findings consistent with MLD who can undergo intrathecal/IV procedures and required follow-up.
Not a fit: Patients with advanced, irreversible neurological damage or those excluded for active uncontrolled infections, HIV, malignancy, major organ dysfunction, or inability to undergo MRI may not receive benefit from this intervention.
Why it matters
Potential benefit: If successful, this therapy could restore ARSA activity, reduce sulfatide buildup, and slow or halt the demyelination that drives neurological decline in MLD.
How similar studies have performed: Ex vivo lentiviral gene therapy using modified hematopoietic stem cells has shown clinical benefit and regulatory approval in MLD, but direct intrathecal/intravenous lentiviral injection is a newer and less-tested approach.
Eligibility criteria
Show full inclusion / exclusion criteria
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.
Where this trial is running
Shenzhen, Guangdong
- Lung-Ji Chang — Shenzhen, Guangdong, China (Recruiting)
Study contacts
- Principal investigator: Lung-Ji Chang, Ph.D — Shenzhen Geno-Immune Medical Institute
- Study coordinator: Lung-Ji Chang, Ph.D
- Email: c@szgimi.org
- Phone: +86 0755-86573763
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.