Methods for identifying and monitoring drug side effects
The present invention relates generally to methods for identifying drug side effects by detecting perturbations in organ-specific molecular blood fingerprints. The invention further relates to methods for identifying drug-specific organ-specific molecular blood fingerprints. As such, the present invention provides compositions comprising organ-specific proteins, detection reagents for detecting such proteins, and panels and arrays for determining organ-specific molecular blood fingerprints.
1. A method for determining the presence or absence of a drug side effect in a subject taking the drug comprising,
(a) detecting a level of each of a plurality of organ-specific proteins in a test blood sample from the subject, wherein the plurality of organ-specific proteins are secreted from the same organ, wherein the organ-specific proteins comprises at least 5 organ-specific proteins;
(b) comparing said level of each of the plurality of organ-specific proteins in the test blood sample from the subject to a level of each of the plurality of organ-specific proteins in a control sample of blood from one or more subjects who have not taken the drug;
wherein a statistically significant altered level of one or more of the plurality of organ-specific proteins in the test blood sample as compared to the control sample is indicative of the presence or absence of a drug side effect.
2. The method of claim 1 wherein the level of each of the plurality of organ-specific proteins is detected using a method selected from the group consisting of mass spectrometry, and an immunoassay.
3. The method of claim 2 wherein the level of each of the plurality of organ-specific proteins is measured using tandem mass spectrometry.
4. The method of claim 2 wherein the level of each of the plurality of organ-specific proteins is measured using ELISA.
5. The method of claim 2 wherein the level of each of the plurality of organ-specific proteins is measured using an antibody array.
6. The method of claim 1 wherein the organ-specific proteins comprise liver-specific proteins.
7. The method of claim 1 wherein the organ-specific proteins comprise kidney-specific proteins.
8. The method of claim 1 wherein the organ-specific proteins are from an organ other than the expected therapeutic target of the drug.
9. The method of claim 1 , wherein the organ-specific proteins comprise at least 10 organ-specific proteins.
10. The method of claim 1 , wherein the organ-specific proteins comprise at least 20 organ-specific proteins.
11. The method of claim 1 , wherein the monitoring is performed during development of the drug.
12. The method of claim 1 , wherein the monitoring is performed after approval of the drug.
13. A method for determining the presence or absence of a drug side effect of a drug for which a first organ is expected to be the therapeutic target, wherein the side effect is associated with a second organ different from the first organ, and wherein the second organ is not the therapeutic target of the drug, the method comprising,
(a) detecting a level of each of a plurality of organ-specific proteins in a test blood sample from a subject taking the drug, wherein the plurality of organ-specific proteins are secreted from the second organ;
(b) comparing the level of each of the plurality of the organ-specific proteins in the test blood sample to a level of each of the plurality of the organ-specific proteins in a control sample of blood from one or more subjects who have not taken the drug, wherein the organ-specific proteins comprises at least 5 organ-specific proteins;
wherein a statistically significant altered level of one or more of the plurality of the organ-specific proteins in the test blood sample as compared to the control sample is indicative of the presence of a drug side effect,
wherein the monitoring is performed during development of the drug.
14. A method for determining the presence or absence of a drug side effect of a drug for which a first organ is expected to be the therapeutic target, wherein the side effect is associated with a second organ different from the first organ, and wherein the second organ is not the therapeutic target of the drug, the method comprising,
(a) detecting a level of each of a plurality of organ-specific proteins in a test blood sample from a subject taking the drug, wherein the plurality of organ-specific proteins are secreted from the second organ;
(b) comparing the level of each of the plurality of the organ-specific proteins in the test blood sample to a level of each of the plurality of the organ-specific proteins in a control sample of blood from one or more subjects who have not taken the drug, wherein the organ-specific proteins comprises at least 5 organ-specific proteins;
wherein a statistically significant altered level of one or more of the plurality of the organ-specific proteins in the test blood sample as compared to the control sample is indicative of the presence of a drug side effect,
wherein the monitoring is performed after approval of the drug.