Enzyme Replacement Therapy in Pompe Disease Clinical Trial
Official title:
Cardiopulmonary Exercise Test to Quantify Enzyme Replacement Response in Pediatric Pompe Disease
Introduction: Enzyme replacement therapy (ERT) with Myozyme improved the prospect of Pompe
disease patients. Our aim was to evaluate ERT acute effect on exercise capacity in pediatric
Pompe patients.
Methods: Pompe patients (10-19 years) were evaluated before and two days after ERT using
cardiopulmonary exercise testing (CPET), six minutes walking test (6MWT) and motor function
test (GMFM-88).
Pompe disease is an inherited autosomal recessive glycogen storage disease caused by partial
or total deficiency of acid α-glucosidase (GAA), resulting in the accumulation of glycogen
in the lysosomes of skeletal muscles, heart, liver and other tissues. There is an inverse
correlation between the amount of residual GAA activity and disease severity. The clinical
phenotype varies with regard to age of onset, organ involvement, and severity of
progression. In 2006, enzyme replacement therapy (ERT) with recombinant human GAA (Genzyme
Corporation, Cambridge MA, USA) was approved and, since then, decisive modification of the
course of the disease has been reported. Clinical studies in infants showed that ERT led to
improvement in cardiac, respiratory and skeletal muscle functions, with achievement of
independent walking, higher levels of physical activity, and survival beyond infancy.
Exercise capacity significantly affects Pompe patients' clinical picture and quality of life
[5]. However, data on the effects of ERT on physiological variables related to exercise
capacity is scarce. Cardiopulmonary exercise testing (CPET) is a well-known procedure to
assess exercise capacity in adults and children in healthy and chronic conditions. Little is
known regarding exercise capacity in the pediatric Pompe population. Our aim was to evaluate
the acute effect of ERT on exercise capacity and different physiological variables in
pediatric Pompe patients.
Patients were evaluated before and two days after ERT (20mg/kg/EOW). Each evaluation
included CPET, pulmonary function tests, 6MWT and GMFM-88. All tests were carried out by the
same experienced physician, exercise physiologist, and physiotherapist.
Visit 1: Patients arrived at that hospital at 7:00 am, vital signs were collected and a
complete neuromuscular evaluation was carried out (gross motor function measure score sheet
(GMFM-88), 6MWT, pre-CPET questionnaire (demographics, physical activity level, risk
assessment, asthma/atopy/smoking history, family history), pulmonary function tests and
CPET. Following the evaluation, at approximately 9 am, the patient started infusion of ERT.
Visit 2: Two days following visit 1, the patient arrived at the hospital at 2:00 pm, vital
signs were assessed and GMFM-88, 6MWT, pulmonary function tests, and CPET were performed.
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