Biomarker for thoracic aortic aneurysm
View Patent ↗A method for detecting thoracic aortic aneurysm (TAA) or predisposition to TAA in a subject comprises measuring the amount of tetrahydrobiopterin (H 4 B) present in the test sample; and comparing a measured amount of HUB to a standard amount of H 4 B. A decreased amount of H 4 B present in the test sample compared to the standard is indicative of TAA or predisposition to TAA. The method can further comprise identifying a candidate for further testing or monitoring for TAA, such as by ultrasound or by repeated testing for H 4 B after one or more designated intervals. The method can also further comprise prescribing treatment for TAA to the subject, such as with folic acid therapy, and/or DHFR therapy, including gene therapy, and other therapies effective for recoupling eNOS and/or therapies targeting uncoupled eNOS. Methods are also described for monitoring the efficacy of treatment of TAA, and for evaluating the severity of TAA or risk of TAA.
1. A method for treating thoracic aortic aneurysm (TAA) in a subject having TAA, the method comprising:
(a) measuring, in a test sample of serum, plasma or whole blood from the subject, the amount of tetrahydrobiopterin (H 4 B) present in the test sample; wherein a decrease is detected in the measured amount of H 4 B present in the test sample relative to a standard amount of H 4 B; and
(b) treating the subject with oral administration of folic acid or dihydrofolate reductase (DHFR) gene therapy.
2. The method of claim 1 , wherein the decrease is a 30% decrease in the amount of H 4 B present in the test sample compared to the standard.
3. The method of claim 1 , wherein the decrease is a 40% decrease in the amount of H 4 B present in the test sample compared to the standard.
4. The method of claim 1 , wherein the decrease is a 50% decrease in the amount of H 4 B present in the test sample compared to the standard.
5. The method of claim 1 , wherein the measuring comprises an immunoassay or a chemiluminescence assay.
6. The method of claim 1 , wherein the measuring comprises high performance liquid chromatography (HPLC).
7. The method of claim 1 , wherein the treating comprises oral administration of folic acid.
8. The method of claim 1 , wherein the decrease is a 20% decrease in the amount of H 4 B present in the test sample compared to the standard.
9. The method of claim 1 , wherein the sample is plasma.
10. The method of claim 1 , further comprising measuring, in a second test sample of serum, plasma or whole blood obtained from the subject at a second time point, the amount of H 4 B present in the second test sample; wherein treatment with folic acid therapy is administered to the subject prior to the second time point.
11. The method of claim 10 , wherein a 20% increase is measured in the amount of H 4 B present in the second test sample compared to the amount of H 4 B measuring in step (a).
12. The method of claim 10 , further comprising prescribing a modified treatment for TAA to the subject whose H 4 B is decreased in the second test sample compared to the amount measured in step (a).
13. The method of claim 1 , further comprising prescribing a modified treatment for TAA to the subject whose H 4 B is insufficiently increased in the second test sample compared to the amount measured in step (a).
14. The method of claim 1 , wherein the decrease is a 60% decrease in the amount of H 4 B present in the test sample compared to the standard.
15. The method of claim 1 , wherein the decrease is a 70% decrease in the amount of H 4 B present in the test sample compared to the standard.
16. The method of claim 1 , wherein the decrease is a 80% decrease in the amount of H 4 B present in the test sample compared to the standard.