Clinical trial NCT03725670: Lentiviral Gene Therapy for MLD
Official title: Gene Therapy for Metachromatic Leukodystrophy (MLD) Using a Self-inactivating Lentiviral Vector (TYF-ARSA)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Metachromatic Leukodystrophy (MLD)
Keywords: Metachromatic leukodystrophy (MLD)
lentiviral vector
Lead sponsor: Shenzhen Geno-Immune Medical Institute
Sponsor class: OTHER
First posted: 2018-10-31
Enrollment: 10
Sex: ALL
Minimum age (years): 1
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a Phase I/II clinical trial of gene transfer for treating Metachromatic leukodystrophy (MLD) using a safety and efficiency 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 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 some 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 efficiency improved self-inactivating lentiviral vector carrying a functional MLD gene to correct the genetic defect by intracerebral injection to delivery the lentiviral vector carrying a normal ARSA gene to correct the pathogenic defect. The primary objectives are to evaluate the safety of the improved self-inactivating lentiviral vector TYF-ARSA, the in vivo gene transfer clinical protocol and the efficacy of degradative metabolite in patients at the time of treatment, assessment of vector integration sites, and finally the long-term correction of the related pathological symptoms.

Eligibility criteria: Inclusion Criteria:

1. MLD patient age \>= 0 year
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.

Primary outcomes:
measure: Safety of intracerebral injection of lentiviral TYF-ARSA.
timeFrame: up to 1 year follow up
measure: Altered disease progression
timeFrame: up to 3 year follow up after treatment
Secondary outcomes:
Other outcomes:
Locations:
city: Shenzhen
country: China
facility: Lung-Ji Chang
state: Guangdong
Study officials:
affiliation: Shenzhen Geno-Immune Medical Institute
name: Lung-Ji Chang, Ph.D
role: PRINCIPAL_INVESTIGATOR
References: