New era in treatment for phenylketonuria: Pharmacologic therapy with sapropterin dihydrochloride

Abstract

Oral administration of sapropterin hydrochloride, recently approved for use by the US Food and Drug Administration and the European Commission, is a novel approach for the treatment of phenylketonuria (PKU), one of the most common inborn errors of metabolism. PKU is caused by an inherited deficiency of the enzyme phenylalanine hydroxylase (PAH), and the pathophysiology of the disorder is related to chronic accumulation of the free amino acid phenylalanine in tissues. Contemporary therapy is based upon restriction of dietary protein intake, which leads to reduction of blood phenylalanine levels. This therapy is difficult to maintain throughout life, and dietary noncompliance is commonplace. Sapropterin dihydrochloride is a synthetic version of tetrahydrobiopterin, the naturally occurring pterin cofactor that is required for PAH-mediated phenylalanine hydroxylation. In a subset of individuals with PAH deficiency, sapropterin administration leads to reduction in blood phenylalanine levels independent of dietary protein. For these individuals, sapropterin is an effective novel therapy for PKU.

Inborn Errors of Metabolism and Brain Involvement - 5 Years Experience from a Tertiary Care Center in South India

“…Vernon et al (2010), Trefz et al (2010), Harding (2010), Burton et al (2010), Somaraju & Merrin (2010) and others report that saptopterin hydrochloride, a synthetic analog of tetrahydrobiopterin, is a promising new drug in the treatment of PKU. This modality of treatment is especially important considering the report by Enns et al (2010) who state that PKU treated with diet alone has sub-optimal outcome with relation to neurocognitive, psychological and physical parameters.…”

Open, Non-Comparative Phase III Clinical Study to Evaluate the Efficacy and Safety of Sapropterin in Patients with Phenylketonuria and Hyperphenylalaninemia

“…Для детей первого года жизни материнское молоко в питании сохра-няют, но ограничивают его потребление (ранее заменяли на детские адаптированные смеси). При искусственном вскармливании предпочтение отдают смесям, содержа-щим меньшее количество белка [9][10][11][12][13].…”

“…В настоящее время наряду с гипофенилаланиновой диетой активно разрабатывают новые методы лечения ГФА [2,[13][14][15][16][17][18], наиболее перспективным из которых представляется терапия сапроптерином. Сапроптерин, или сапроптерина дигидрохлорид (Куван, Мерк КГаА и Ко, Австрия) -искусственно синтезированный экви-валент природного 6R-тетрагидробиоптерина (6R-BH 4 ), который является кофактором гидроксилаз фенилалани-на, тирозина и триптофана.…”

Optimized loading test to evaluate responsiveness to tetrahydrobiopterin (BH4) in Brazilian patients with phenylalanine hydroxylase deficiency

“…Studies, however, have used different protocols to evaluate responsiveness: BH 4 doses are different and may range from 10 to 20 mg/kg/day in a single dose or distributed along the day; test evaluation times range from some hours to weeks or even months; the cut-off point of Phe variation defined to determine responsiveness also varies, and the criterion most frequently adopted is a decrease of 30% in Phe levels 24 h after BH 4 administration. In addition, different diets are used during tests: normal diets, Phe-restricted diet, or even a Phe-loading diet using, for example, powder milk or L-Phe [7,[9][10][11][12][13][14][15][16][17][18][19][20][21][22].…”