Method for treating or preventing a cardiovascular disease or condition utilizing estrogen receptor modulators based on APOE allelic profile of a mammalian subject

• US 20100022497A1
• Filed: 05/29/2009
• Published: 01/28/2010
• Est. Priority Date: 07/24/2008
• Status: Abandoned Application

• Current Assignee: Searete LLC (Intellectual Ventures LLC)
• Original Assignee: Searete LLC (Intellectual Ventures LLC)
• Inventors: Ishikawa, Muriel Y., Wood, Lowell L. JR., Rivet, Dennis J., Hyde, Roderick A., Sweeney, Elizabeth A., Wood, Victoria Y.H., Leuthardt, Eric C.
• Application Number:
  US12/455,272
• Publication Number:
  US 20100022497A1
• Time in Patent Office: Days
• US Class Current: 514/182
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/00 Medicinal preparations containing organic active ingredients
• CPC Class Codes: A61K 31/415 1,2-Diazoles
• CPC Class Codes: A61K 31/423 condensed with carbocyclic rings
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system

Abstract

A method for treating cardiovascular disease in a mammalian subject includes providing to the subject at least one treatment regimen including at least one estrogen receptor modulator, wherein the at least one treatment regimen is determined based on the APOE allelic profile in the subject, and based on the steroid hormone levels prior to disease diagnosis and on current steroid hormone levels in the subject.

Claims

1. A method for treating a cardiovascular disease or condition in a mammalian subject comprising:

providing to the mammalian subject at least one estrogen receptor modulator, wherein the at least one estrogen receptor modulator is determined based on an APOE allelic profile in the mammalian subject, and wherein the mammalian subject has at least one reduced steroid hormone level compared to a steroid hormone level prior to disease diagnosis.

2. The method of claim 1, wherein the subject'"'"'s APOE allelic profile is at least one of APOE ε

2 positive and APOE ε

3 positive.

3. The method of claim 2, wherein the at least one estrogen receptor modulator includes at least one selective estrogen receptor α

agonist.

4. The method of claim 2, wherein the subject'"'"'s APOE allelic profile is ε

4 negative.

5. The method of claim 1, further including providing at least one treatment regimen including at least one replacement therapy including one or more steroid hormones or metabolites or modulators thereof.

6. The method of claim 5, wherein the at least one treatment regimen including the least one replacement therapy is configured to increase levels of one or more of an estrogen or a progestogen, or metabolites or modulators thereof.

7. The method of claim 5, wherein the at least one treatment regimen includes replacement therapy with one or more of an estrogen or a progestogen.

9. The method of claim 1, wherein the subject'"'"'s APOE allelic profile is ε

4 positive.

10. The method of claim 9, wherein the at least one estrogen receptor modulator includes at least one selective estrogen receptor β

agonist.

12. The method of claim 1, wherein the at least one estrogen receptor modulator is configured to maintain the subject'"'"'s one or more steroid hormones or metabolites or modulators thereof at substantially physiological pre-disease cyclic levels, and the at least one estrogen receptor modulator is in an amount effective to reduce the cardiovascular disease or condition or alleviate symptoms thereof in the subject.

13. The method of claim 1, wherein the mammalian subject is female.

14. The method of claim 13, wherein the mammalian subject is perimenopausal or postmenopausal.

15. The method of claim 13, wherein the at least one estrogen receptor modulator is determined at least in part based on the premenopausal cyclic steroid hormone levels in the mammalian subject and on current cyclic steroid hormone levels in the mammalian subject.

16. The method of claim 1, wherein the mammalian subject is male.

18. The method of claim 1, further including providing to the mammalian subject at least one treatment regimen including at least one aromatase inhibitor.

19. The method of claim 1, further including providing to the mammalian subject at least one treatment regimen including at least one or more of an estrogen receptor α

antagonist or an estrogen receptor β

antagonist.

20. The method of claim 1, further including providing to the mammalian subject at least one treatment regimen including one or more of an aromatase inhibitor, an estrogen receptor α

antagonist or an estrogen receptor β

antagonist.

21. The method of claim 1, wherein the at least one estrogen receptor modulator is configured to maintain the subject'"'"'s one or more steroid hormones or metabolites or modulators thereof at substantially physiological pre-disease levels.

22. The method of claim 1, wherein the current cyclic steroid hormone levels are based on steroid hormone levels during a period of disease in the subject.

23. The method of claim 1, further including determining the one or more steroid hormones levels in the subject during a treatment period.

24. The method of claim 23, wherein the treatment period includes a time period preceding treatment with the at least one estrogen receptor modulator.

25. The method of claim 23, wherein the treatment period includes a time period during treatment with the at least one estrogen receptor modulator.

26. The method of claim 25, wherein the determining of the one or more steroid hormones levels occurs at multiple time points during the treatment period.

27. The method of claim 23, further including providing to the subject the at least one estrogen receptor modulator and at least one treatment regimen including at least one replacement therapy including one or more steroid hormones or metabolites or modulators thereof configured to maintain the subject'"'"'s one or more steroid hormones or one or more metabolites or modulators thereof at substantially physiological levels.

29. The method of claim 1, further including determining a genetic profile including at least an APOE profile of the subject.

30. The method of claim 5, wherein the at least one treatment regimen is determined based at least in part on one or more of a time-history of serum steroid hormone levels in the subject, on inferred peak values or minimal values of serum steroid hormone levels in the subject, on age of the subject, or on categorization relative to profiles of patient populations.

31. The method of claim 5, wherein the at least one treatment regimen is determined based at least in part on Fourier analysis of the cyclic steroid hormone levels in the subject, or on harmonic analysis of the cyclic steroid hormone levels in the subject.

32. The method of claim 5, wherein the at least one treatment regimen is determined based at least in part on scaled values of the steroid hormone levels prior to the disease diagnosis in the subject.

33. The method of claim 32, wherein the at least one treatment regimen is determined based at least in part on the scaled value approximately equal to one.

34. The method of claim 32, wherein the at least one treatment regimen is determined based at least in part on the scaled value dependent on age of the subject.

8. (canceled)

11. (canceled)

17. (canceled)

28. (canceled)

35-97. -97. (canceled)

98. A method for treating a cardiovascular disease or condition in a perimenopausal or menopausal mammalian subject, the subject characterized as having one or both of APOE ε

2 positive or APOE ε

3 positive allelic profile, the method comprising;

administering an estrogen receptor-α

agonist in an amount and for a time sufficient to increase expression of one or both of an APOE ε

2 or APOE ε

3 gene; and

administering at least one replacement therapy including one or more steroid hormones or metabolites or modulators thereof in an amount and for a time sufficient to cause the mammalian subject'"'"'s steroid hormone level to be substantially similar to the mammalian subject'"'"'s premenopausal steroid hormone level.

99. The method of claim 98, wherein the subject'"'"'s APOE allelic profile is ε

4 negative.

100. The method of claim 98, wherein the at least one treatment regimen including the least one replacement therapy is configured to increase levels of one or more of an estrogen and a progestogen, or metabolites or modulators thereof.

103. The method of claim 98, wherein the at least one estrogen receptor modulator is configured to maintain the subject'"'"'s one or more steroid hormones or metabolites or modulators thereof at substantially physiological pre-disease cyclic levels, and the at least one estrogen receptor modulator is in an amount effective to reduce the cardiovascular disease or condition or alleviate symptoms thereof in the subject.

101. (canceled)

102. (canceled)

104-123. -123. (canceled)

124. A method for treating a cardiovascular disease or condition in a perimenopausal or menopausal mammalian subject, the subject characterized as having APOE ε

4 positive allelic profile, the method comprising;

administering an estrogen receptors agonist in an amount and for a time sufficient to decrease expression of an APOE ε

4 gene; and

administering at least one replacement therapy including one or more steroid hormones or metabolites or modulators thereof in an amount and for a time sufficient to cause the mammalian subject'"'"'s steroid hormone level to be substantially similar to the mammalian subject'"'"'s premenopausal steroid hormone level.

125. The method of claim 124, wherein the at least one treatment regimen including the least one replacement therapy is configured to increase levels of one or more of an estrogen and a progestogen, or metabolites or modulators thereof.

128. The method of claim 124, wherein the at least one estrogen receptor modulator is configured to maintain the subject'"'"'s one or more steroid hormones or metabolites or modulators thereof at substantially physiological pre-disease cyclic levels, and the at least one estrogen receptor modulator is in an amount effective to reduce the cardiovascular disease or condition or alleviate symptoms thereof in the subject.

144. The method of claim 124, wherein the at least one treatment regimen is determined based at least in part on one or more of a time-history of serum steroid hormone levels in the subject, on inferred peak values or minimal values of serum steroid hormone levels in the subject, on age of the subject, or on categorization relative to profiles of patient populations.

126. (canceled)

127. (canceled)

129-143. -143. (canceled)

145-148. -148. (canceled)

149. A method for preventing a cardiovascular disease or condition in a perimenopausal or menopausal mammalian subject, the subject characterized as having one or both of APOE ε

2 positive or APOE ε

3 positive allelic profile, the method comprising;

administering an estrogen receptor-α

agonist in an amount and for a time sufficient to increase expression of one or both of the APOE ε

2 or APOE ε

3 gene; and

administering at least one replacement therapy including one or more steroid hormones or metabolites or modulators thereof in an amount and for a time sufficient to cause the mammalian subject'"'"'s steroid hormone level to be substantially similar to the mammalian subject'"'"'s premenopausal steroid hormone level.

150. The method of claim 149, wherein the subject'"'"'s APOE allelic profile is ε

4 negative.

151. The method of claim 149, wherein the at least one treatment regimen including the least one replacement therapy is configured to increase levels of one or more of an estrogen and a progestogen, or metabolites or modulators thereof.

154. The method of claim 149, wherein the at least one estrogen receptor modulator is configured to maintain the subject'"'"'s one or more steroid hormones or metabolites or modulators thereof at substantially physiological pre-disease cyclic levels, and the at least one estrogen receptor modulator is in an amount effective to reduce the cardiovascular disease or condition or alleviate symptoms thereof in the subject.

152. (canceled)

153. (canceled)

155-174. -174. (canceled)

175. A method for preventing a cardiovascular disease or condition in a perimenopausal or menopausal mammalian subject, the subject characterized as having APOE ε

4 positive allelic profile, the method comprising;

administering an estrogen receptor-β

agonist in an amount and for a time sufficient to decrease expression of an APOE ε

4 gene; and

administering at least one replacement therapy including one or more steroid hormones or metabolites or modulators thereof in an amount and for a time sufficient to cause the mammalian subject'"'"'s steroid hormone level to be substantially similar to the mammalian subject'"'"'s premenopausal steroid hormone level.

176. The method of claim 175, wherein the at least one treatment regimen including the least one replacement therapy is configured to increase levels of one or more of an estrogen and a progestogen, or metabolites or modulators thereof.

179. The method of claim 175, wherein the at least one estrogen receptor modulator is configured to maintain the subject'"'"'s one or more steroid hormones or metabolites or modulators thereof at substantially physiological pre-disease cyclic levels, and the at least one estrogen receptor modulator is in an amount effective to reduce the cardiovascular disease or condition or alleviate symptoms thereof in the subject.

195. The method of claim 175, wherein the at least one treatment regimen is determined based at least in part on one or more of a time-history of serum steroid hormone levels in the subject, on inferred peak values or minimal values of serum steroid hormone levels in the subject, on age of the subject, or on categorization relative to profiles of patient populations.

177. (canceled)

178. (canceled)

180-194. -194. (canceled)

196-210. -210. (canceled)