Sapropterin Dihydrochloride

In multiple sclerosis patients, plasma biopterin (a tetrahydrobiopterin precursor) was persistently low and correlated with higher disability (EDSS), while neopterin (a bypass product) was elevated. In a mouse model of autoimmune encephalomyelitis (EAE), treatment with the BH4 drug sapropterin worsened disease scores, increased spinal cord T‑cell infiltration, and altered lipid profiles (increased long‑chain ceramides, decreased linolenic acid) that disrupt the blood‑brain barrier. Gene expression analysis confirmed upregulation of ceramide synthesis enzymes in brain endothelial cells. BH4 fortifies autoimmune CNS disease and should not be supplemented in MS.

Fig. 1 Effects of sapropterin medication on the disease severity in EAE mice. (Schmitz K, et al., 2021)

The SPARK extension study (51 children <4 years with BH₄‑responsive phenylketonuria or mild hyperphenylalaninemia) evaluated long‑term sapropterin plus a Phe‑restricted diet over 36 additional months. In the continuous sapropterin group, dietary Phe tolerance increased by 38.7 mg/kg/day (P<0.0001). The group that initiated sapropterin at week 27 showed a smaller, non‑significant increase (5.5 mg/kg/day). Both groups maintained normal neuromotor development and growth. Long‑term sapropterin is safe and effective, but frequent monitoring of blood Phe and careful dietary titration are essential.

Fig. 2 A Dietary Phe tolerance during the extension period. b Dietary Phe tolerance (mg/kg/day) change in baseline during the extension period. (Muntau AC, et al., 2021)