Use of relaxin to treat placental syndromes
View Patent ↗The subject application relates to methods for treating a placental syndrome, wherein relaxin is administered during the late secretory/luteal (LS) phase of the menstrual cycle in women who have a propensity for developing the placental syndrome. In certain embodiments, administration of relaxin continues beyond the LS phase and into pregnancy.
1. A method for treating a placental syndrome in a woman comprising the steps of: (a) identifying a woman who has experienced a placental syndrome during a previous pregnancy; (b) determining the late secretory/luteal (LS) phase of the menstrual cycle of the woman from step (a); and (c) administering a therapeutically effective amount of relaxin to the woman from step (a) only during the LS phase of the menstrual cycle to treat the placental syndrome, wherein the LS phase of the menstrual cycle refers to the phase that commences several days following ovulation in the woman.
2. The method according to claim 1 , wherein the relaxin is an RXFP-1 agonist or mimetic.
3. The method according to claim 1 , wherein determination of the LS phase of the menstrual cycle is performed using a kit that is able to detect LH surge.
4. The method according to claim 1 , wherein the therapeutically effective amount of relaxin is 0.1 to about 100 μg/kg of subject body weight per day.
5. The method according to claim 4 , wherein the administration of the relaxin results in serum concentrations of relaxin of about 0.1-10.0 ng/ml during the LS phase of the menstrual cycle.
6. The method according to claim 4 , wherein administration of the relaxin results in serum concentrations of relaxin of about 0.1-3.0 ng/ml during the LS phase of the menstrual cycle.
7. The method according to claim 1 , further comprising the step of (d) determining whether the woman is pregnant and (e) if the woman is determined to be pregnant following step (d), administering a therapeutically effective amount of relaxin to the woman through the 1 st trimester of pregnancy.
8. The method according to claim 7 , wherein the relaxin is an RXFP-1 agonist or mimetic.
9. The method according to claim 1 , wherein the placental syndrome is preeclampsia.
10. A method for treating a placental syndrome in a woman comprising the steps of: (a) determining that a woman has a propensity for developing a placental syndrome; (b) determining the late secretory/luteal (LS) phase of the menstrual cycle of the woman from step (a); and (c) administering a therapeutically effective amount of a relaxin to the woman of step (a) only during the LS phase of the menstrual cycle,
wherein the LS phase of the menstrual cycle refers to the phase that commences several days following ovulation in the woman.
11. The method according to claim 10 , wherein the relaxin is an RXFP-1 agonist or mimetic.
12. The method according to claim 10 , wherein determination of the LS phase of the menstrual cycle is performed using a kit that is able to detect LH surge.
13. The method according to claim 10 , wherein the therapeutically effective amount of relaxin is 0.1 to about 100 μg/kg of subject body weight per day.
14. The method according to claim 13 , wherein administration of the relaxin results in serum concentrations of relaxin of about 0.1-10.0 ng/ml during the LS phase of the menstrual cycle.
15. The method according to claim 13 , wherein administration of the relaxin results in serum concentrations of relaxin of about 0.1-3.0 ng/ml during the LS phase of the menstrual cycle.
16. The method according to claim 10 , further comprising the step of (d) determining whether the woman is pregnant and (e) if the woman is determined to be pregnant following step (d), administering a therapeutically effective amount of relaxin (or RXFP-1 agonist or mimetic) to the woman through the 1 st trimester of pregnancy.
17. The method according to claim 10 , wherein the placental syndrome is preeclampsia.
18. The method according to claim 17 , wherein step (a) comprises:
obtaining a biological sample from the woman during the LS phase;
performing analysis of the biological sample to determine whether the following one or more genes are downregulated: ALDH1L2; RORB; EPAS1; DLGAP1; SPOCK1; MAOB; GZMB; IL2RB; GNLY; NOG; TRA@; MUC15; KLRC2; IL15; CHRDL1; PRL; SCARA5; CHST6; NTN1; CPM; IL1B; ITGB6; MMP12; BDKRB2; SLC16A6; FN1; PP14; FSTL3; WT1; IGFBP1; CFH/CFHR1; C3; C4BPA; Flt-4; HTR2B; and ERAP2; and
performing analysis of the biological sample to determine whether the following one or more genes are upregulated: ACOT8; BICD1; ADCYAP1R1; DPYSL4; COL5A1; FOSB; CR1; and S100A8.
19. The method according to claim 18 , wherein step (a) further comprises the use of an immunoassay for (i) binding one or more polypeptide species in the biological sample to an antibody and quantitatively determining the amount of said one or more polypeptide species in said biological sample to determine downregulation or upregulation of the one or more genes, and (ii) comparing the amount of the polypeptide species from step (i) to a standard control representing the amount of the polypeptide species in the corresponding sample from an average non-preeclamptic woman, wherein an increase or a decrease in the amount of the polypeptide species from the standard control indicates upregulation or downregulation of the one or more genes.
20. The method according to claim 19 , wherein said immunoassay is selected from the group consisting of: a radioimmunoassay, ELISA (enzyme-linked immunosorbant assay), sandwich immunoassay, immunoradiometric assay and Western blot.
21. The method according to claim 18 , wherein the biological sample can be blood, washing from the reproductive tract, urine, saliva, or endometrial biopsy.
22. The method according to claim 17 , wherein step (a) comprises:
obtaining a biological sample from the woman during the LS phase;
quantitatively determining the amount of endogenous relaxin in the biological sample; and
comparing the amount of the quantified amount of endogenous relaxin to a standard control representing the amount of the endogenous relaxin in the corresponding sample from a woman without symptoms of placental syndromes; wherein an increase and decrease in the amount of the endogenous relaxin in the biological sample as compared to the standard control indicates an increased risk of developing preeclampsia.
23. The method according to claim 22 , wherein the step of quantitatively determining the amount of endogenous relaxin in the biological sample comprises determining the amount of one or more nucleic acid species in the biological sample that hybridizes with any one or more probe set for RLN-1, RLN-2, RLN-3 and RXFP1.