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

Background: The current standard of care for infantile-onset Pompe disease (IOPD), a severe form of acid α-glucosidase enzyme activity deficiency is: (1) detection by newborn screening, (2) early initiation of intravenous enzyme replacement therapy (ERT) using recombinant human acid alpha-glucosidase (rhGAA), with higher doses of rhGAA increasingly used to improve clinical outcomes, and (3) immune tolerization induction (ITI) using to prevent anti-rhGAA antibody formation, with methotrexate (MTX), rituximab, and IVIG used for patients who are cross-reactive immunologic material negative (CRIM-) and monotherapy with MTX used in patients who are cross-reactive immunologic material positive (CRIM+). Objectives/methods: A pilot study evaluates a dose-intensive therapy (DIT) using high-dose ERT (40 mg/kg/week) and more frequent exposure to ERT (i.e., 3 times weekly administration) to mitigate anti-rhGAA antibody formation, as an alternative to the standard therapeutic approach for IOPD. Results: In the first patient, DIT resulted in rapid normalization of the following: (1) bi-ventricular hypertrophy, (2) urine HEX-4, (3) CK, (4) liver transaminases. At 7 years of age, the patient continues the DIT regimen. To date, all pediatric developmental milestones have been met on time, anti-rhGAA antibodies have been negative and the patient is able to attend school and maintain normal activities of daily living. Conclusions: Over a 7-year period, DIT for CRIM-positive IOPD was well tolerated in the first patient treated. Excellent clinical outcomes were achieved, and anti-rhGAA antibodies levels were consistently undetectable. Assessments of more patients, that includes patients with CRIM-, as well as CRIM+ IOPD, will determine if this approach consistently achieves improved clinical outcomes and immune tolerization.