Cardiovascular Disease
6R-BH4 (also referred to as tetrahydrobiopterin or BH4) is a naturally occurring enzyme cofactor that is required for numerous biochemical and physiologic processes, including the synthesis of nitric oxide (NO).
6R-BH4 at a Glance
Nitric Oxide plays a key protective role throughout the cardiovascular system. It has multiple positive effects, such as relaxing smooth muscle, reducing blood pressure, controlling inflammation and reducing platelet aggregation. Nitric Oxide is synthesized in the endothelium in a process that involves the enzyme endothelial nitric oxide synthase (eNOS), the substrate arginine, and the essential enzyme cofactor BH4. A deficiency of BH4 can disrupt Nitric Oxide synthesis, resulting in a loss of normal endothelial Nitric Oxide production. This loss of endothelial Nitric Oxide production is commonly referred to as endothelial dysfunction. Endothelial dysfunction has been associated with many cardiovascular diseases, including hypertension, diabetic vascular disease, peripheral arterial disease, coronary arterial disease and pulmonary hypertension, and has been shown to be a strong predictor of cardiovascular adverse events in a number of clinical studies.
In academic studies, researchers have demonstrated that administration of BH4 improves vascular endothelial function in animal models and in patients with diabetes and other cardiovascular diseases.
Development Status
BioMarin is currently evaluating the potential application of 6R-BH4 in treating pulmonary hypertension.