Tetrahydrobiopterin (BH4) is a cofactor of the enzyme phenylalanine hydroxylase, essential to many bodily functions and one that may improve blood circulation in people with COPD. Although COPD is a lung disease, recent studies indicate that it carries multiple systemic consequences, including the vascular endothelial dysfunction that is a cause of cardiovascular disease.
In fact, researchers note that more COPD patients die from cardiovascular disease than from direct pulmonary complications.
How does tetrahydrobiopterin for COPD work?
BH4 is a substance (called cofactor) that is needed in the synthesis of nitric oxide. It is also used to convert amino acids into other essential molecules in the body, and is involved in cellular events mediated by nitric oxide production, such as the programmed death of the cells (apoptosis) and inflammation.
Researchers believe that the mechanisms that contribute to less nitric oxide being available — resulting in vascular endothelial dysfunction in people with COPD — are important because such dysfunction is an independent predictor of such cardiovascular disorders as hypertension, coronary artery disease, and heart failure. [The endothelium is a thin layer that covers the inner surface of blood vessels, and works to modulate the vascular smooth muscle cells that produce relaxation or contraction, meaning vasodilatation or vasoconstriction.]
People with COPD usually have a poor pulmonary function, inflammation, and free-radical production, which leads to a greater incidence of cardiovascular problems. It is this unbalance between free-radical generation and antioxidant defenses that makes for high oxidative stress and, subsequently, cardiovascular disorders.
Studies of tetrahydrobiopterin
A study (NCT01398943) tried to identify the role of nitric oxide bioavailability in contributing to vascular endothelial dysfunction in people with COPD, and to discover the mechanisms involved. It suggested that inflammation and oxidative stress contribute independently to less nitric oxide availability, and thus to vascular endothelial dysfunction in people with COPD.
A Phase 2 study (NCT02774226), taking place at one site in Augusta, Georgia, is currently recruiting participants. This study is evaluating long-term nitric oxide bioavailability on vascular health in people with COPD. Participants will have either a 12-week treatment with BH4 or an antioxidant cocktail (with vitamins C, E and alpha lipoic acid). Its primary objective is measures of the change in flow mediated dilation, a common test of vascular endothelial function. Measures will also be made of changes in blood markers of oxidative stress, femoral and carotid tonometry (a measurement used to assess arterial stiffness), and iontophoresis and local heating, which measure microvascular function. Collection of data on the study’s outcomes is expected to finish in September 2017.
A synthetic form of tetrahydrobiopterin, available under the brand name Kuvan (sapropterin dihydrochloride), is an approved treatment for a rare inherited disorder known as phenylketonuria. This disease is due to a defect in the gene that helps to create the enzyme needed to break down phenylalanine, which is ingested through foods.
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