Therapeutic approaches for neuronopathic lysosomal storage disorders

Area of Science:

• Neuroscience
• Genetics
• Biochemistry

Background:

• Central nervous system (CNS) involvement in lysosomal storage diseases (LSDs) presents significant therapeutic challenges.
• The intact blood-brain barrier restricts efficient delivery of therapeutic agents to the CNS.

Purpose of the Study:

• To review current and emerging therapeutic strategies for CNS manifestations of LSDs.
• To highlight the potential of various approaches in overcoming blood-brain barrier limitations.

Main Methods:

• Review of existing literature on LSDs and CNS therapies.
• Analysis of non-specific therapies (e.g., hematopoietic stem cell transplantation), anti-inflammatory agents, enzyme replacement therapy, small molecules, and gene therapy.

Main Results:

• Hematopoietic stem cell transplantation shows utility in specific LSDs like Krabbe disease.
• Enzyme replacement therapy (high-dose, modified enzymes) and small molecules demonstrate promise for CNS correction.
• Gene therapy is under development, and combination approaches are anticipated.

Conclusions:

• A combination of therapeutic strategies, informed by disease mechanisms, is likely essential for treating the neurological complications of LSDs.
• Overcoming the blood-brain barrier remains a critical factor for successful CNS-targeted therapies in LSDs.