Asfotase alfa restores PLP-dependent GABA, cystathionine, and amino acid metabolism in a mouse model of hypophosphatasia.

This study assessed whether asfotase alfa treatment in Akp2-/- mice (a model of hypophosphatasia) reversibly normalizes GABA and cystathionine in brain tissue to concentrations in wild-type mice. To do this, metabolite concentrations were analyzed at postnatal days 10 and 48. The data showed that asfotase alfa treatment significantly increased GABA concentrations and significantly decreased cystathionine concentrations in Akp2-/- mice compared with vehicle-treated Akp2-/- mice (GABA: 1.28 ± 0.03 vs 0.48 ± 0.02 μmol/g [P < 0.0001]; cystathionine: 0.06 ± 0.00 vs 0.60 ± 0.02 μmol/g [P < 0.0001]). Concentrations post-treatment were similar to those in wild-type mice. Asfotase alfa withdrawal negated these effects. These analyses demonstrated that asfotase alfa restores GABA and cystathionine concentrations in a murine model of hypophosphatasia.