Manipulation of androgen receptors in treatment of hair loss

United States Patent     5,556,956

Roy, et al.     Sept. 17, 1996

Methods and compositions relating to the androgen receptor gene and uses thereof.



Roy; Arun K. (San Antonio, TX); Chatterjee; Bandana (San Antonio, TX).



Board of Regents, The University of Texas System (Austin, TX).


Appl. No:




Nov. 4, 1993


Related U.S. Application Data:

Intl. Cl.: C07H 21/00, C07H 21/02, C07H 21/04

Current U.S. Cl.: 536/24.1; 536/23.1; 536/24.3; 536/24.31

Field of Search: 536/24.1, 24.31, 24.3, 23.1; 514/44



Disclosed are methods and compositions, including antisense and antigene constructs and pharmaceutical formulations thereof, for use in regulating androgen receptor gene expression. The promoter activity of the androgen receptor gene is herein shown to include a critical upstream acting domain with a unique sequence, the unique nucleic acid sequence corresponding to positions 1697 and 2084, particularly between positions 1697 and 1717, as defined in SEQ ID NO:1. The AR gene promoter sequence, herein characterized as having a a particular nucleotide sequence defined between nucleotides 1697 and 2084 of SEQ ID NO:1, is characterized as important in the regulation of androgen receptor gene expression. Oligonucleotides and triple helix forming oligonucleotides (TFO) that bind to this region and that have nucleic acid sequences corresponding particularly to the region between positions 1697 and 2084 of the androgen receptor gene promoter region provide specific and potent inhibition of AR promoter region function in cellulo. Rat and human nuclear proteins, more specifically described as novel trans-activating proteins that specifically bind to this region of the androgen receptor gene, are also identified. These proteins may be used to prepare specific antibodies to the protein, as well as to regulate the expression of the AR gene. The oligonucleotide compositions of the invention may be used as molecular probes for the androgen receptor gene, as well as to inhibit the expression of the androgen receptor gene. The compositions may also be used in the treatment of pathologies characterized by overexpression of the androgen receptor gene, including prostatic hypertrophy and androgenetic alopecia.

15 Claims, 7 Drawing Figures

The government owns rights in the subject matter of the claimed invention as research was funded by NIH grants R01-AG- 63527 NIH grant P01-AG 06872, and NIH grant R 37-DK 14744.


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Dialog Search Report dated Jan. 26, 1994.
Primary Examiner: Fleisher; Mindy
Assistant Examiner: Schmickel; David
Attorney, Agent or Firm: Akin, Gump, Strauss, Hauer & Feld, L.L.P.