Gene therapy using patients' own stem cells for treating specific genetic disorders

A Phase I/II Clinical Trial of Lentiviral Hematopoietic Stem Cell Gene Therapy for Treatment of Developed Metachromatic Leukodystrophy and Adrenoleukodystrophy

This study is testing a new gene therapy that uses patients' own stem cells to see if it can help people with serious genetic disorders like Metachromatic Leukodystrophy and Adrenoleukodystrophy feel better and slow down their disease.

Quick facts

• Phase: PHASE1; PHASE2
• Study type: Interventional
• Enrollment: 50 (estimated)
• Ages: 1 Year to 16 Years
• Sex: All
• Sponsor: Shenzhen Second People's Hospital (other)
• Locations: 1 site (Shenzhen, Guangdong)
• Trial ID: NCT02559830 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the safety and efficacy of a novel gene therapy approach using lentiviral vectors to transfer specific genes into hematopoietic stem cells for patients with advanced stages of Metachromatic Leukodystrophy (MLD) and Adrenoleukodystrophy (ALD). The study aims to treat these severe genetic disorders characterized by progressive neurodegeneration by correcting the underlying genetic defects in patients' own stem cells. Participants will receive transduced CD34+ hematopoietic stem cells, which are expected to improve their condition and potentially halt disease progression.

Who should consider this trial

Good fit: Ideal candidates are children under 16 years old with confirmed diagnoses of MLD or ALD who have not reached the end stage of their respective diseases.

Not a fit: Patients who are at the pre-symptomatic stage or have reached the end stage of MLD or ALD will not benefit from this study.

Why it matters

Potential benefit: If successful, this therapy could significantly improve the quality of life and outcomes for patients suffering from MLD and ALD.

How similar studies have performed: Previous studies have shown promise with similar gene therapy approaches in treating severe forms of these disorders, indicating potential for success.

Eligibility criteria

Inclusion Criteria:

Inclusion Criteria For MLD:

1. Confirmed diagnosis as MLD by ARSA genetic diagnosis, MRI（Magnetic Resonance Imaging）and low ARSA A activity (below 20% of normal level);
2. The patient' symptoms and lesions have not been developed to the end stage of MLD.
3. age \< 16.0 years at symptom onset

Inclusion Criteria For ALD:

1. Confirmed diagnosis as ALD by ABCD1 genetic diagnosis, abnormal MRI imaging, abnormal high level of very long chain fatty acid (VLCFA) and adrenocorticotropic hormone (ACTH);
2. The patient' symptoms and lesions have not been developed to the end stage of ALD.
3. age \< 16.0 years at symptom onset

Exclusion Criteria:

Exclusion Criteria For MLD：

1. At a pre-symptomatic stage of of MLD;
2. ARSA activity \>50% compared to healthy individuals;
3. End stage of MLD;
4. Other complications, ie. Cancer;
5. human immunodeficiency virus（HIV） RNA and/or hepatitis C virus RNA and/or hepatitis B virus DNA positive patients;
6. Patients who underwent allogenic hematopoietic stem cell transplantation with evidence of residual cells of donor origin.
7. Serious organ dysfunction;
8. were enrolled in other clinical trials in the 6 months prior to screening;
9. had any other concern that hampered the compliance or safety as judged by the investigator;
10. Adult

Exclusion Criteria For ALD:

1. No evidence of brain lesions;
2. Normal level of VLCFAs in blood;
3. End stage of ALD;
4. Other complications, ie. Cancer;
5. human immunodeficiency virus（HIV） RNA and/or hepatitis C virus RNA and/or hepatitis B virus DNA positive patients;
6. Patients who underwent allogenic hematopoietic stem cell transplantation with evidence of residual cells of donor origin.
7. Serious organ dysfunction;
8. were enrolled in other clinical trials in the 6 months prior to screening;
9. had any other concern that hampered the compliance or safety as judged by the investigator;
10. Adult

Where this trial is running

Shenzhen, Guangdong

• Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University — Shenzhen, Guangdong, China (RECRUITING)

Study contacts

• Principal investigator: Qizhou Lian, M.D.,Ph.D. — The University of Hong Kong
• Study coordinator: JiaCai zhou, M.D.,Ph.D

Conditions: Metachromatic Leukodystrophy, Adrenoleukodystrophy