BoneKEy Reports | BoneKEy Watch
Enzyme-replacement therapy for hypophosphatasia
DOI:10.1038/bonekey.2012.122
This study represents the first human trial of therapeutic enzyme replacement therapy for hypophospotasia. Caused by mutations in the gene that encodes a tissue-nonspecific isozyme of alkaline phosphatase (TNSALP), hypophosphatasia usually causes premature infant death due to respiratory problems and severe bone disease. Previous studies have shown that ENB-0040, a recombinant human TNSALP, prevents some of the more serious aspects of the disease in mice that have had their TNSALP gene knocked out.
Eleven young children with severe infantile or perinatal hypophosphatasia were given ENB-0040 treatment, which targets bone specifically. A single infusion of ENB-0040 (40 mg/ml) was given at the start of treatment, with dosing at 2 mg/kg body weight. Half that dose as repeated injections was then given three times a week. For infants who did not show improvements, or who actually deteriorated, the dose was increased to 3 mg/kg.
The nine patients who completed 12 months of therapy showed reduced evidence of rickets by 6 months, general skeletal healing and also improved pulmonary function and achievement of developmental milestones. The treatment appeared to be well tolerated with no sign of serious adverse events after 48 weeks.
Editor's comment: A therapeutic revolution; children with this currently untreatable and devastating genetic disorder show improvement of skeletal abnormalities and physical function after recombinant enzyme replacement therapy.
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