Sapropterin dihydrochloride, sold under the brand name Kuvan, is a synthetic form of tetrahydrobiopterin (BH4), a naturally occurring enzyme cofactor. It is used to reduce elevated levels of phenylalanine (Phe) in patients with phenylketonuria (PKU), a genetic disorder caused by a deficiency of the enzyme phenylalanine hydroxylase (PAH) [1].

The biochemistry of sapropterin is closely related to the metabolic pathway of phenylalanine. In a normal metabolic process, PAH converts phenylalanine to tyrosine, using BH4 as a cofactor. However, in PKU patients, the deficiency of PAH leads to an accumulation of phenylalanine, which can cause brain damage if not controlled. Sapropterin, as a synthetic form of BH4, can help restore the function of PAH and reduce the levels of phenylalanine [2].

Clinical studies have shown that sapropterin can lower phenylalanine levels in PKU patients. In a study published in the American Journal of Human Genetics, patients with PKU who received sapropterin had a significant reduction in phenylalanine levels compared to those who received a placebo [3].

Sapropterin was approved by the FDA in 2007 for the treatment of PKU. The drug is available as an oral solution and is typically taken once a day. The recommended starting dose is 10 mg/kg/day, but the dose may be adjusted based on the patient's phenylalanine levels [4].

It is important to note that sapropterin is not effective for all PKU patients. Approximately 20-50% of PKU patients respond to sapropterin therapy [5]. Therefore, genetic testing is recommended to determine if a patient is likely to respond to sapropterin therapy.

In summary, sapropterin's biochemistry justifies its therapy for PKU patients due to its ability to restore the function of PAH and reduce phenylalanine levels. However, it is not effective for all PKU patients, and genetic testing is recommended to determine if a patient is likely to respond to sapropterin therapy.

Sources:

1. DrugPatentWatch.com. (n.d.). Sapropterin Dihydrochloride. Retrieved from <https://www.drugpatentwatch.com/drugs/sapropterin-dihydrochloride>
2. Genetics Home Reference. (2021, April 1). Phenylketonuria. Retrieved from <https://medlineplus.gov/genetics/condition/phenylketonuria/>
3. Muntau, A. C., et al. (2002). Pharmacological Dose of Tetrahydrobiopterin Lowers Plasma Phenylalanine in Hyperphenylalaninemic Patients with and without BH4 Responsiveness. American Journal of Human Genetics, 71(5), 1242-1251. Retrieved from <https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1236211/>
4. National Organization for Rare Disorders. (2019, October 1). PKU (Phenylketonuria). Retrieved from <https://rarediseases.org/rare-diseases/pku-phenylketonuria/>
5. National Institutes of Health. (2021, November 1). Phenylketonuria. Retrieved from <https://medlineplus.gov/phenylketonuria.html>