Enzyme Replacement Therapy & Other Therapeutic Frontiers in…

Research question

What can enzyme replacement therapy (ERT) currently achieve for metabolic disorders presenting in infancy, and where are its limits?

Clinical & scientific significance

The review argues for investment in research, expanded newborn screening and equitable access so that early, innovative treatment can reach affected infants.

Key findings reported in the paper

Early intravenous recombinant acid alpha-glucosidase has markedly improved survival and cardiac function in infants with Pompe disease.
Persistent challenges include immunogenicity, limited penetration into the central nervous system and variable skeletal-muscle response.
In utero ERT, gene therapy, gene editing, substrate reduction and stem-cell transplantation are discussed as emerging or complementary strategies.
Barriers include high cost, limited global access and the need for long-term outcome surveillance.

Objectives

To review the evolution, clinical use and emerging innovations of ERT, with a focus on disorders presenting in the neonatal and infantile period.

Methods

Narrative review, using infantile-onset Pompe disease as the central example and extending to other infantile disorders and complementary therapies.

This summary is based only on the published abstract.

Enzyme replacement therapy in infants

01
Missing enzyme
A genetic change leaves an enzyme absent or not working.
General background
02
Substrate builds up
Unprocessed material accumulates and damages tissue.
General background
03
Replacing the enzyme
Early intravenous recombinant enzyme has improved survival and cardiac function in Pompe disease.
04
Known limits
Immune response to the enzyme, limited entry into the brain, variable muscle response.
05
Emerging approaches
Treatment before birth, gene therapy and editing, substrate reduction, stem-cell transplantation.

Concepts reviewed in NeoReviews 2025. Illustrative overview, not a treatment guide. Conceptual illustration — not experimental data.

Read the publication

Metabolism

Authors

Choi HJ, Sriram A, Sargiotto C, Fajardo-Martinez V

Citation

Enzyme Replacement Therapy & Other Therapeutic Frontiers in Infantile Metabolic Disorders. Neoreviews. 2025; 26(12):e835-e846. doi:10.1542/neo.26-12-081. PMID: 41319976.

Enzyme Replacement Therapy & Other Therapeutic Frontiers in Infantile Metabolic Disorders