Dose-intensive therapy (DIT) for infantile Pompe disease: A pilot study

Area of Science:

• Biochemistry
• Genetics
• Pediatrics

Background:

• Infantile-onset Pompe disease (IOPD) is a severe lysosomal storage disorder caused by acid alpha-glucosidase deficiency.
• Current standard of care involves enzyme replacement therapy (ERT) with recombinant human acid alpha-glucosidase (rhGAA) and immune tolerization induction (ITI).
• Treatment strategies vary based on cross-reactive immunologic material (CRIM) status, with different approaches for CRIM-positive and CRIM-negative patients.

Observation:

• A pilot study investigated dose-intensive therapy (DIT) with high-dose ERT (40 mg/kg/week, thrice weekly) as an alternative to standard care for IOPD.
• The first patient, diagnosed with CRIM-positive IOPD, received DIT.
• Clinical assessments included bi-ventricular hypertrophy, urine HEX-4, creatine kinase (CK), and liver transaminases.

Findings:

• DIT resulted in rapid normalization of cardiac, biochemical, and liver markers in the first patient.
• The patient met all developmental milestones on time and maintained normal daily activities.
• Anti-rhGAA antibodies remained undetectable throughout the 7-year treatment period, and the therapy was well tolerated.

Implications:

• DIT may offer an effective alternative to standard ERT and ITI for managing IOPD, potentially improving clinical outcomes and immune tolerance.
• Further studies involving larger cohorts, including CRIM-negative patients, are needed to confirm the consistent efficacy and safety of DIT.
• This approach could lead to improved long-term management and quality of life for children with IOPD.