InformationaboutBH4Whatitisandhowitworks.docxVIP

Sponsored by: Singh Research Group Emory University Department of Human Genetics Information about BH4: What it is and how it works Updated on November 20th, 2008 KuvanTM is a pharmaceutical (prescription drug) with a structure very similar to a natural compound humans make called Tetrahydrobiopterin (BH4). KuvanTM comes in pill form and is usually taken once a day with meals. Response to KuvanTM is currently defined by the medical community as a 30% or greater decrease in plasma Phe levels. Approximately 50% of all people with PKU respond this way to KuvanTM. Both severe and mild forms of PKU can respond to KuvanTM, however, those with milder forms of PKU do have a greater chance of responding General Information about BH4 BH4 Molecule Structures BH4 (Tetrahydrobiopterin) As it is naturally made by the body KuvanTM (Sapropterin Dihydrochloride) Pharmaceutical with structure similar to natural BH4 Reference for structures: /chemidplus/chemidheavy.jsp Phenylalanine (Phe) and Tyrosine (Tyr) are essential amino acids that the body must have to function properly. But too much of these amino acids in the blood can be toxic. BH4 is a cofactor naturally made by the body which the PAH (phenylalanine hydroxylase) enzyme uses to convert Phe into Tyr. For most people, this keeps the body’s Phe and Tyrosine in a healthy balance. How BH4 works to convert Phe to Tyrosine PAH BH4 Phe Tyr People with PKU make the same amount of natural BH4 as people without PKU. However, in PKU the PAH enzyme is malformed and does not function very well. This can cause Phe to increase to toxic levels inside the body. Providing extra BH4, in the form of KuvanTM, has been shown to increase the ability of the defective PAH enzyme to convert Phe into Tyrosine for some people who have PKU How can taking KuvanTM help someone with PKU? PAH BH4 Phe Tyr BH4 BH4 At the Emory Genetics Clinic: We obtain a baseline plasma Phe level You are prescribed 20mg/kg/day dose of KuvanTM For the next several days