TY  - JOUR
UR  - http://dx.doi.org/10.1358/dot.2023.59.2.3461911
ID  - discovery10168772
N2  - Metachromatic leukodystrophy (MLD) is a rare autosomal recessive disorder of sphingolipid metabolism, due to a deficiency of the enzyme arylsulfatase A (ARSA). The main clinical signs of the disease are secondary to central and peripheral nervous system demyelination. MLD is subdivided into early and lateonset subtypes based upon the onset of neurological disease. The earlyonset subtype is associated with a more rapid progression of the disease that leads to death within the first decade of life. Until recently, no effective treatment was available for MLD. The blood?brain barrier (BBB) prevents systemically administered enzyme replacement therapy from reaching target cells in MLD. The evidence for the efficacy of hematopoietic stem cell transplantation is limited to the lateonset MLD subtype. Here, we review the preclinical and clinical studies that facilitated the approval of the ex vivo gene therapy atidarsagene autotemcel for earlyonset MLD by the European Medicines Agency (EMA) in December 2020. This approach was studied in an animal model first and then in a clinical trial, eventually proving its efficacy in preventing disease manifestations in presymptomatic patients and stabilizing its progression in paucisymptomatic subjects. This new therapeutic consists of patients? CD34+ hematopoietic stem/progenitor cells (HSPCs) transduced with a lentiviral vector encoding functional ARSA cDNA. The genecorrected cells get reinfused into the patients after a cycle of chemotherapy conditioning.
Y1  - 2023/02/01/
JF  - Drugs of Today
A1  - Messina, M
A1  - Gissen, P
PB  - PROUS SCIENCE, SAU-THOMSON REUTERS
SP  - 63
VL  - 59
EP  - 70
IS  - 2
AV  - public
SN  - 1699-3993
TI  - Atidarsagene autotemcel for metachromatic leukodystrophy
KW  - Science & Technology
KW  -  Life Sciences & Biomedicine
KW  -  Pharmacology & Pharmacy
KW  -  Atidarsagene autotemcel
KW  -  Metachromatic leukodystrophy
KW  -  - Arylsulfatase A (ARSA) mimetics
KW  -  Lysosomal storage diseases
KW  -  Gene therapy
KW  -  LYSOSOMAL STORAGE DISORDERS
KW  -  CELL GENE-THERAPY
KW  -  OPEN-LABEL
N1  - This version is the author accepted manuscript. For information on re-use, please refer to the publisher?s terms and conditions.
ER  -