Detection and treatment of conditions related to luteinizing hormone/follicle-stimulating hormone (LH/FSH) levels

Patent metadata

Field	Value
Publication number	US-12442827-B2
Application number	US-202017775040-A
Country	US
Kind code	B2
Filing date	Nov 5, 2020
Priority date	Nov 7, 2019
Publication date	Oct 14, 2025
Grant date	Oct 14, 2025

Abstract

Provided herein are methods for detecting or predicting a disease or condition related to a ratio of luteinizing hormone to follicle-stimulating hormone (LH/FSH ratio) by obtaining or having obtained a biological sample from a subject; and determining the LH/FSH ratio in the biological sample, wherein a decrease in the LH/FSH ratio when compared to an age-matched subject that does not have a disease or condition of LH/FSH is indicative of a current or future disease or condition of LH/FSH.

First claim

What is claimed is:

1. A method for treating a disease or condition of the eye related to a ratio of luteinizing hormone to follicle-stimulating hormone (LH/FSH ratio) comprising:
obtaining or having obtained a biological sample from a subject;
determining the LH/FSH ratio in the biological sample, wherein a decrease in the LH/FSH ratio when compared to an age-matched subject that does not have a disease or condition of the eye related to an LH/FSH ratio is indicative of a current or future disease or condition of the eye related to an LH/FSH ratio in the subject;
and administering to the subject with a decrease in the LH/FSH ratio an effective amount of gonadotropes, pituitary hormones, Gonadotropin-releasing hormones, LH, FSH, dehydroepiandrosterone sulfate (DHEA-S), Estrone, Estriol, or sex hormones, with a Prolactin-Inducible Protein (PIP) or a Gonadotropin-releasing hormone (GNRH) in an amount sufficient to increase the LH/FSH ratio.

2. The method of claim 1 , wherein the disease or condition of the eye is Keratoconus; or is Keratoconus and a severity of Keratoconus is determined by measuring a decrease in the LH/FSH ratio for Keratoconus levels KC-1, KC-2, KC-3 and KC-4.

3. The method of claim 1 , wherein a first biological sample is obtained at a first time that is before, during, or after puberty, and a second biological sample is obtained at a second time after the first time, wherein a decrease in the LH/FSH ratio between the first and second time is predictive of Keratoconus when the second sample is obtained prior to symptoms of Keratoconus.

4. The method of claim 1 , wherein the biological sample is a blood, plasma, tear, intravitreal, blood-serum, hair, urine, aqueous humor, saliva or sweat sample.

5. The method of claim 1 , further comprising detecting at least one of dehydroepiandrosterone (DHEA) or dehydroepiandrosterone sulfate (DHEA-S) in the biological sample, wherein an increase in DHEA or DHEA-S when compared to an age-matched subject is indicative of Keratoconus; or further comprising detecting in the biological sample at least one of estrone, estriol, or gonadotropin-releasing hormone, wherein a decrease of estrone, estriol, gonadotropin-releasing hormone, or combinations thereof when compared to an age-matched subject, is indicative of Keratoconus.

6. A method of treating a subject that will develop a disease or condition of the eye related to a ratio of luteinizing hormone to follicle-stimulating hormone (LH/FSH ratio) comprising:
obtaining or having obtained a biological sample from the subject;
determining a level of expression of LH and FSH in the biological sample;

calculating the LH/FSH ratio in the biological sample;
determining if there is a decrease in the LH/FSH ratio when compared to an age-matched subject that does not have a disease or condition of the eye related to an LH/FSH ratio, wherein a decrease in the LH/FSH ratio is indicative of a current or future disease or condition of the eye related to an LH/FSH ratio in need of treatment; and

administering to the subject with a decrease in the LH/FSH ratio an effective amount of gonadotropes, pituitary hormones, Gonadotropin-releasing hormones, LH, FSH, dehydroepiandrosterone sulfate (DHEA-S), Estrone, Estriol, or sex hormones, with a Prolactin-Inducible Protein (PIP) or a Gonadotropin-releasing hormone (GNRH) in an amount sufficient to increase the LH/FSH ratio.

7. The method of claim 6 , wherein the disease or condition of the eye is Keratoconus; or is Keratoconus and a severity of Keratoconus is determined by measuring a decrease in the LH/FSH ratio for Keratoconus levels KC-1, KC-2, KC-3 and KC-4.

8. The method of claim 6 , wherein a first biological sample is obtained at a first time that is before, during, or after puberty, and a second biological sample is obtained at a second time after the first time, wherein a decrease in the ratio of LH/FSH between the first and second time is predictive of Keratoconus, and the second sample is obtained prior to symptoms of Keratoconus.

9. The method of claim 6 , wherein the biological sample is a blood, plasma, tear, intravitreal, blood-serum, hair, urine, aqueous humor, saliva or sweat sample.

10. The method of claim 6 , further comprising detecting at least one of dehydroepiandrosterone (DHEA) or dehydroepiandrosterone sulfate (DHEA-S) in the biological sample, wherein an increase in DHEA or DHEA-S when compared to an age-matched subject is indicative of Keratoconus; or further comprising detecting in the biological sample at least one of estrone, estriol, or gonadotropin-releasing hormone, wherein a decrease of estrone, estriol, gonadotropin-releasing hormone, or combinations thereof when compared to an age-matched subject, is indicative of Keratoconus.

11. The method of claim 6 , wherein an amount of a Prolactin-Inducible Protein (PIP) effective to treat the disease or condition of the eye is administered to the subject.

12. A method for treating a patient with a disease or condition of the eye related to a ratio of luteinizing hormone to follicle-stimulating hormone (LH/FSH ratio), the method comprising the steps of:
performing or having performed a determination of the LH/FSH ratio in a biological sample obtained from a patient suspected of having a disease or condition of the eye related to an LH/FSH ratio; and
administering to the subject with a decrease in the LH/FSH ratio as compared to an age-matched control that does not have a disease or condition of the eye related to an LH/FSH ratio, an effective amount of gonadotropes, pituitary hormones, Gonadotropin-releasing hormones, LH, FSH, dehydroepiandrosterone sulfate (DHEA-S), Estrone, Estriol, or sex hormones, with a Prolactin-Inducible Protein (PIP) or a Gonadotropin-releasing hormone (GNRH) in an amount sufficient to increase the LH/FSH ratio.

13. The method of claim 12 , wherein the PIP is provided in an amount of 0.1 ng/ml to 1 mg/ml or the GNRH is provided in an amount of 0.1 pg/ml to 1 mg/ml.

14. The method of claim 12 , wherein the disease or condition of the eye is Keratoconus; or is Keratoconus and a severity of Keratoconus is determined by measuring a decrease in the LH/FSH ratio for Keratoconus levels KC-1, KC-2, KC-3 and KC-4.

15. A method of treating a patient with Keratoconus comprising:
obtaining a sample of corneal stromal cells from a patient suspected of having Keratoconus;
determining a level of expression of luteinizing hormone receptor (LHR), follicle stimulating hormone receptor (FSHR), or both in the sample, wherein an increase in LHR, or a decrease of FHSR, or both as compared to an age matched subject that does not have keratoconus, is indicative of Keratoconus; and
administering to the patient with Keratoconus a composition comprising an effective amount of gonadotropes, pituitary hormones, Gonadotropin-releasing hormones, LH, FSH, dehydroepiandrosterone sulfate (DHEA-S), Estrone, Estriol, or sex hormones, and a Prolactin-Inducible Protein (PIP) or a Gonadotropin-releasing hormone (GNRH) in an amount sufficient to increase an LH/FSH ratio in the patient.

16. The method of claim 15 , wherein the PIP is provided in an amount of 0.1 ng/ml to mg/ml or the GNRH is provided in an amount of 0.1 pg/ml to 1 mg/ml.

17. The method of claim 15 , wherein the composition is formulated for topical, or ophthalmic.

18. The method of claim 17 , wherein the composition is delivered into the conjunctival sac of the patient or administered to the patient by intravitreal, subconjunctival, retrobulbar, intracameral, or sub-Tenon's administration.

Assignees

• Univ Of North Texas Health Science Center At Fort Worth
• Univ Oklahoma

Inventors

• Karamichos Dimitrios

Classifications

• G01N2800/04

  Endocrine or metabolic disorders · CPC title

• G01N2333/59

  Follicle-stimulating hormone [FSH]; Chorionic gonadotropins, e.g. HCG; Luteinising hormone [LH]; Thyroid-stimulating hormone [TSH] · CPC title

• C07K14/59

  Follicle-stimulating hormone [FSH]; Chorionic gonadotropins, e.g.hCG [human chorionic gonadotropin]; Luteinising hormone [LH]; Thyroid-stimulating hormone [TSH] · CPC title

• A61K38/22

  Hormones (derived from pro-opiomelanocortin, pro-enkephalin or pro-dynorphin A61K38/33, e.g. corticotropin A61K38/35) · CPC title

• A61P27/02

  Ophthalmic agents · CPC title