NCT01560182

Gene Therapy for Metachromatic Leukodystrophy (MLD)

Completed Phase 1, PHASE2 Last updated 5 December 2025

What this trial tests

Phase 1, PHASE2 trial testing OTL-200 Gene Therapy in Lysosomal Storage Disease in 20 participants. Completed in 19 September 2025.

Timeline

9 April 2010

Primary endpoint
9 April 2018

19 September 2025

Quick facts

Lead sponsor	Orchard Therapeutics
Phase	Phase 1, PHASE2
Status	Completed
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	20
Start date	9 April 2010
Primary completion	9 April 2018
Estimated completion	19 September 2025
Sites	1 location across Italy

Drugs / interventions tested

• OTL-200 Gene Therapy

Conditions studied

• Lysosomal Storage Disease — all drugs for Lysosomal Storage Disease →
• Metachromatic Leukodystrophy — all drugs for Metachromatic Leukodystrophy →

Sponsor

Orchard Therapeutics — full company profile →

Who can join

Under 7, any sex, with Lysosomal Storage Disease or Metachromatic Leukodystrophy. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

This Phase I/II clinical trial consists of the application of lentiviral vector-based gene therapy to patients affected by Metachromatic Leukodystrophy (MLD), a rare inherited Lysosomal Storage Disorder (LSD) resulting from mutations in the gene encoding the Arylsulfatase A (ARSA) enzyme. The medicinal product consists of autologous CD34+ hematopoietic stem/progenitor cells in which a functional ARSA cDNA is introduced by means of 3rd generation VSV-G pseudotyped lentiviral vectors.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Lentiviral haemopoietic stem-cell gene therapy in early-onset metachromatic leukodystrophy: an ad-hoc analysis of a non-randomised, open-label, phase 1/2 trial.
   Sessa M, Lorioli L, Fumagalli F, Acquati S, et al · · 2016 · cited 384× · PMID 27289174 · DOI 10.1016/s0140-6736(16)30374-9
2. Lentiviral haematopoietic stem-cell gene therapy for early-onset metachromatic leukodystrophy: long-term results from a non-randomised, open-label, phase 1/2 trial and expanded access.
   Fumagalli F, Calbi V, Natali Sora MG, Sessa M, et al · · 2022 · cited 212× · PMID 35065785 · DOI 10.1016/s0140-6736(21)02017-1
3. Clinical development of gene therapy: results and lessons from recent successes.
   Kumar SR, Markusic DM, Biswas M, High KA, et al · · 2016 · cited 155× · PMID 27257611 · DOI 10.1038/mtm.2016.34
4. A systematic review and meta-analysis of gene therapy with hematopoietic stem and progenitor cells for monogenic disorders.
   Tucci F, Galimberti S, Naldini L, Valsecchi MG, et al · · 2022 · cited 109× · PMID 35288539 · DOI 10.1038/s41467-022-28762-2
5. Metachromatic Leukodystrophy: Diagnosis, Modeling, and Treatment Approaches.
   Shaimardanova AA, Chulpanova DS, Solovyeva VV, Mullagulova AI, et al · · 2020 · cited 81× · PMID 33195324 · DOI 10.3389/fmed.2020.576221
6. Update on Clinical Ex Vivo Hematopoietic Stem Cell Gene Therapy for Inherited Monogenic Diseases.
   Tucci F, Scaramuzza S, Aiuti A, Mortellaro A. · · 2021 · cited 72× · PMID 33221437 · DOI 10.1016/j.ymthe.2020.11.020
7. Correction of brain oligodendrocytes by AAVrh.10 intracerebral gene therapy in metachromatic leukodystrophy mice.
   Piguet F, Sondhi D, Piraud M, Fouquet F, et al · · 2012 · cited 69× · PMID 22642214 · DOI 10.1089/hum.2012.015
8. Gene therapy for metachromatic leukodystrophy.
   Rosenberg JB, Kaminsky SM, Aubourg P, Crystal RG, et al · · 2016 · cited 61× · PMID 27638601 · DOI 10.1002/jnr.23792