Biotechnological and Cellular Therapies in the Treatment of Neurodegenerative Leukodystrophies

Abstract

Leukodystrophies are inherited neurodegenerative disorders characterized by progressive white matter damage, historically lacking effective treatments beyond symptomatic management and hematopoietic stem cell transplantation. This review analyzes contemporary biotechnological strategies, including gene therapy, cell-based approaches, and antisense oligonucleotides. Approved products like Libmeldy for metachromatic leukodystrophy and Skysona for adrenoleukodystrophy demonstrate that ex vivo lentiviral modification of autologous stem cells can stabilize neurological function when administered early. In vivo gene therapy using AAV vectors and antisense oligonucleotides targeting toxic protein accumulation show encouraging results in clinical studies. Despite challenges regarding blood-brain barrier delivery and immunogenicity, recent advances indicate a paradigm shift toward personalized genomic medicine. These innovations offer potential to halt disease progression and improve long-term outcomes for patients with previously untreatable conditions.