Compositions and methods of treatment of androgen-associated baldness using antisense oligomers
AssigneeGenta Incorporated
InventorsMary Ellen Harper, Tod Mitchell Woolf, Lyle John Arnold, Jr.
Life of this patent
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Abstract
Compositions and methods of treating androgen-associated hair loss, in particular decreasing the progression of male pattern baldness using a nucleoside Oligomer or Oligomers useful in the described methods are provided.
Claims35
A method of decreasing androgen-associated hair loss by decreasing levels of protein-bound 5-alpha-dihydrotestosterone present in scalp tissue without significantly interfering with testosterone metabolism in other tissues, which comprises:
- exposing scalp cells to an effective amount of an Oligomer which interacts with a gene coding for androgen receptor or 5-alpha-reductase or its transcription product or a target sequence immediately upstream from the transcription start site of said gene and thereby inhibits or alters expression of the androgen receptor or 5-alpha-reductase.
A method of decreasing androgen-associated hair loss by decreasing levels of protein-bound 5-alpha-dihydrotestosterone in scalp tissue without significantly interfering with testosterone metabolism in other tissues, which comprises:
- exposing scalp cells to an amount of an Oligomer sufficient to decrease protein-bound 5-alpha-dihydrotestosterone in said scalp cells and decrease the rate of hair loss whereby said Oligomer specifically recognizes a nucleic acid target sequence selected from the group consisting of:
- (a) single stranded RNA,
- (b) single stranded DNA,
- (c) double stranded DNA
- (d) double stranded RNA,
- (e) a DNA/RNA duplex, and
- (f) a single RNA or DNA strand contained within a duplex, whereby the Oligomer selectively interferes with transcription or translation of the nucleic acid target sequence and wherein said nucleic acid target sequence comprises a gene coding for the androgen receptor or 5-alpha-reductase or a transcription product thereof or a sequence immediately upstream from the transcription start site of the gene.
A method of treating androgen-associated hair loss by decreasing levels of protein-bound 5-alpha-dihydrotestosterone present in scalp tissue without significantly interfering with testosterone metabolism in other tissues, which comprises:
- exposing scalp cells to an amount of an Oligomer sufficient to decrease protein-bound 5-alpha-dihydrotestosterone in said scalp cells to produce a decrease in rate of hair loss wherein said Oligomer is selected from the group consisting of:
- (a) an antisense Oligomer having a sequence complementary to a sequence of RNA transcribed from a target gene present in the cells;
- (b) an antisense Oligomer having a nucleoside sequence complementary to a single stranded DNA target sequence;
- (c) an antisense Oligomer having a nucleoside sequence complementary to a single RNA or DNA strand contained within a duplex;
- (d) a Third Strand Oligomer having a sequence complementary to a selected double stranded nucleic acid sequence of a target sequence present in the cells;
- and
- (e) a Triplex Oligomer Pair which is complementary to a single stranded nucleic acid sequence of a target gene or its transcription product or to a single strand of a duplex and wherein said target gene is selected from the group consisting of those genes encoding 5-alpha-reductase and the androgen receptor or a sequence immediately upstream from the transcription start site of said gene.
A method of treating androgen-associated hair loss which comprises:
- exposing scalp to a hair loss rate diminishing amount of an Oligomer selected from the group consisting of:
- (a) an antisense Oligomer having a sequence complementary to a sequence of RNA transcribed from a gene for the androgen receptor, and
- (b) an antisense oligomer having a sequence complementary to a sequence of RNA transcribed from a gene for 5-.alpha.-reductase.
A method of decreasing levels of protein-bound 5-alpha-dihydrotestosterone in a selected tissue without significantly interfering with testosterone metabolism in other tissues or systemically, which comprises:
- exposing cells of the selected tissue with an effective amount of an Oligomer which interacts with a gene coding for androgen receptor or 5-alpha-reductase or its transcription product or a target sequence immediately upstream from the transcription start site of said gene and thereby inhibits or alters expression of the androgen receptor or 5-alpha reductase.
Dependencies are inferred from the claim text.