Enzyme replacement therapy (ERT) is a treatment approach that involves administering exogenous enzymes to compensate for deficient or defective endogenous enzymes. While historically successful for lysosomal storage disorders, ERT is being explored for neurodegenerative diseases where specific enzyme deficiencies contribute to pathology, or where enzyme administration can reduce toxic protein accumulation. [1]
Enzyme replacement therapies work through several mechanisms: [2]
Several lysosomal storage disorders cause neurodegenerative phenotypes: [3]
| Disorder | Enzyme | Therapy Status | [4]
|----------|--------|----------------|
| Gaucher disease (Type 2/3) | β-glucocerebrosidase | Approved (Cerezyme, Vpriv) |
| Pompe disease | Acid α-glucosidase | Approved (Myozyme, Lumizyme) |
| Fabry disease | α-galactosidase A | Approved (Fabrazyme, Replagal) |
| Mucopolysaccharidosis I | α-L-iduronidase | Approved (Aldurazyme) |
| Mucopolysaccharidosis II | Iduronate sulfatase | Approved (Idursulfase) |
The main challenge for CNS-directed ERT:
| Drug | Indication | Route | Status |
|---|---|---|---|
| Brineura (cerliponase alfa) | CLN2 disease | Intracerebroventricular | Approved |
| Cerezyme (imiglucerase) | Gaucher disease | IV | Approved |
| Myozyme (algucosidase alfa) | Pompe disease | IV | Approved |
| Fabrazyme (agalsidase beta) | Fabry disease | IV | Approved |
Enzyme replacement may be combined with:
Schiffmann et al. Enzyme replacement therapy for Gaucher disease and Parkinson's (2024). 2024. ↩︎
Schultz et al. Cerliponase alfa for CLN2 disease (2024). 2024. ↩︎
M. B. de Arriba et al. Enzyme delivery across the BBB (2024). 2024. ↩︎
G. J. L. K. et al. Aβ-degrading enzymes for AD (2023). 2023. ↩︎