CNSA-001 is an oral formulation of synthetic sepiapterin, a precursor to tetrahydrobiopterin (BH4), a crucial cell enzyme involved in various metabolic pathways. After intestinal absorption of sepiapterin into circulation, sepiapterin is actively transported into cells and rapidly converted into tetrahydrobiopterin. Sepiapterin has major advantages over direct tetrahydrobiopterin supplementation in terms of gut absorption, stability in-vivo, sensitivity to oxidation, transport through cell membrane, and ability to cross the blood brain barrier. As a result, sepiapterin induces a higher intracellular concentration of tetrahydrobiopterin in key tissues such as, liver, brain and peripheral neurons, resulting in significant improvement or even normalization of phenylalanine metabolism and the production of neurotransmitters like nitric oxide, dopamine and serotonin.


Sepiapterin is converted by sepiapterin reductase into tetrahydrobiopterin, an essential cofactor of phenylalanine hydroxylase, tyrosine hydroxylase, tryptophan hydroxylase and nitric oxide synthase. These enzymes facilitate the metabolism of phenylalanine to tyrosine and the production of neurotransmitters like dopamine, serotonin, and nitric oxide. It has been demonstrated in vivo that dose dependent increases in intracellular tetrahydrobiopterin can correct a deficiency in the natural cofactor and/or an abnormal function of tetrahydrobiopterin dependent enzymes.


Phase I clinical evaluation of CNSA-001 (Sepiapterin), a novel pharmacological treatment for phenylketonuria and tetrahydrobiopterin deficiencies, in healthy volunteers

Exploratory study of the effect of one week of orally administered CNSA-001 (sepiapterin) on CNS levels of tetrahydrobiopterin, dihydrobiopterin and monoamine neurotransmitter metabolites in healthy volunteers