Isotopic biomarkers of organic acidemias
AssigneeThe United States of America, as represented by the Secretary, Dept.of Health and Human Services
InventorsCharles P. VENDITTI, Irini MANOLI
Life of this patent
Estimating the term…
Abstract
Methods of using isotopic biomarkers in determining the efficacy of a treatment for an organic acidemia in a subject are disclosed herein. Methods of using isotopic biomarkers in determining the efficacy of a liver-directed treatment for an organic acidemia in a subject are likewise disclosed herein.
Claims24
A method for determining the efficacy of a treatment for an organic acidemia in a subject, the method comprising:
- prior to the treatment:
- (i) administering to the subject a composition having isotope-labeled propionate;
- (ii) collecting breath samples from the subject at a plurality of time points after step (i);
- (iii) measuring the 13CO2/12CO2 ratio of the breath samples from step (ii);
- (iv) determining a first isotope-labeled propionate oxidation rate based on the measured 13CO2/12CO2 ratio of step (iii) and measured CO2 production rate;
- following the treatment:
- (v) administering to the subject a composition having isotope-labeled propionate;
- (vi) collecting breath samples from the subject at a plurality of time points after step (v);
- (vii) measuring the 13CO2/12CO2 ratio of the breath samples from step (vi);
- (viii) determining a second isotope-labeled propionate oxidation rate based on the measured 13CO2/12CO2 ratio of step (vii) and measured CO2 production rate;
- and
- comparing the first isotope-labeled propionate oxidation rate with the second isotope-labeled propionate oxidation rate, wherein an increase in the second isotope-labeled propionate oxidation rate compared to the first isotope-labeled propionate oxidation rate indicates efficacy of the treatment.
14-16. (canceled)
21-22. (canceled)
A method for improving hepatic enzyme activity in a subject having an organic acidemia, the method comprising:
- prior to a treatment:
- (i) administering to the subject a composition having sodium isotope-labeled propionate;
- (ii) collecting breath samples from the subject at a plurality of time points after step (i);
- (iii) measuring 13CO2/12CO2 ratio of the breath samples from step (ii);
- (iv) determining a first isotope-labeled propionate oxidation rate based on the measured 13CO2/12CO2 ratio of step (iii) and measured CO2 production;
- administering a treatment to the subject to improve compromised hepatic enzyme activity associated with the organic acidemia after step (ii);
- following the treatment:
- (v) orally administering to the subject a composition having isotope-labeled propionate;
- (vi) collecting breath samples from the subject at a plurality of time points after step (v);
- (vii) measuring 13CO2/12CO2 ratio of the breath samples from step (vi);
- (viii) determining a second isotope-labeled propionate oxidation rate based on the measured 13CO2/12CO2 ratio of step (vii) and measured CO2 production rate;
- discontinuing, altering, or continuing the treatment based on the second isotope-labeled propionate oxidation rate after treatment compared to the first isotope-labeled propionate oxidation rate before the treatment.
25-30. (canceled)
A method for determining the efficacy of a treatment for an organic acidemia in a subject, the method comprising:
- After the treatment:
- (i) administering an isotope-labeled metabolite to the subject wherein the isotope-labeled metabolite is 1-13C-propionate, 1-13C-glycine, or 1-13C-methionine;
- (ii) measuring a level of an isotope-labeled product of the isotope-labeled metabolite in exhaled breath of the subject following administration of the isotope-labeled metabolite;
- (iii) comparing the measured level of isotope-labeled product of the isotope-labeled metabolite in the subject to a predetermined level;
- wherein an increase in the measured level of isotope-labeled product compared to the predetermined level indicates efficacy of the treatment.
32-37. (canceled)
Dependencies are inferred from the claim text.