Tetrahydrobiopterin, an essential enzyme involved in the production of nitric oxide, plays a key protective role in the cardiovascular system. In patients with sickle cell disease, inflammation and production of superoxide (a highly reactive form of oxygen) in blood vessels may decrease levels of tetrahydrobiopterin, creating a deficiency. Restoring tetrahydrobiopterin levels could potentially improve endothelial function, alleviating this complication associated with sickle cell disease.
A total of 27 patients with sickle cell disease were treated every four weeks with escalating doses of tetrahydrobiopterin (2.5, 5, 10, and 20 mg/kg/day). The primary endpoint of the study was the overall safety and efficacy of tetrahydrobiopterin as measured by a non-invasive fingertip test (PAT) that scores endothelial dysfunction. A value of less than or equal to 1.67 represents endothelial dysfunction. At the start of the study, 18 patients had abnormal mean PAT scores (1.33 ± 0.17) and nine patients had normal mean PAT scores (2.09 ± 0.31).
More than one-third (67 percent) of patients with abnormal PAT scores achieved statistically significant dose-dependent improvements in endothelial dysfunction over 16 weeks of tetrahydrobiopterin treatment (2.5 mg/kg: 24 percent improvement; 5mg/kg: 31.2 percent improvement; 10 mg/kg: 39.9 percent improvement; and, 20 mg/kg: 56.6 percent improvement). Patients with normal PAT scores showed no improvement with therapy, which is consistent with the mechanism of action of tetrahydrobiopterin.
This was designed as a safety study, and additional studies in larger numbers of patients will be needed to confirm these preliminary data on the use of tetrahydrobiopterin for the treatment of endothelial dysfunction in patients with s
|SOURCE American Society of Hematology|
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