Treatment of lysosomal storage disorders: cell therapy and gene therapy

Area of Science:

• Neuroscience
• Genetics
• Biotechnology

Background:

• Lysosomal storage diseases (LSDs) frequently impact the central nervous system (CNS).
• Currently, no effective treatments exist for the neurological manifestations of LSDs.
• Mouse models are crucial for investigating therapeutic strategies.

Purpose of the Study:

• To evaluate the efficacy of brain-directed gene therapy and cell therapy for LSDs.
• To assess the therapeutic potential for neurological symptoms in LSD mouse models.

Main Methods:

• Gene therapy involved injecting a recombinant adenovirus encoding beta-galactocerebrosidase into twitcher mice (Krabbe disease model).
• Cell therapy utilized genetically engineered human neural stem cells overexpressing beta-glucuronidase, transplanted into MPS VII mice (beta-glucuronidase deficiency model).

Main Results:

• Gene therapy in Krabbe disease models improved neurological symptoms, prolonged lifespan, increased enzyme activity, and reduced toxic metabolite levels.
• Cell therapy in MPS VII models demonstrated successful integration and migration of transplanted cells, reduced substrate accumulation, and cleared lysosomal storage.
• Both therapeutic approaches showed significant improvements in brain pathology.

Conclusions:

• Brain-directed gene and cell therapies offer a potential treatment strategy for neurological complications associated with lysosomal storage diseases.
• These findings support further investigation into gene and cell-based interventions for CNS-involved LSDs.