Boston University

Barbara A Gilchrest

Mina Yaar

Mark S Eller

Philip R Gordon

Hee-Young Park

Described are methods for treating hyperproliferative disorders, including cancers, by administering to the affected mammal (e.g., human) an effective amount of a composition comprising one or more oligonucleotides which share at least 33% but less than 100% nucleotide sequence identity with the human telomere overhang repeat. Methods of treatment or prevention of hyperproliferative diseases or pre-cancerous conditions affecting epithelial cells, such as psoriasis, atopic dermatitis, or hyperprolferative diseases of other epithelia and methods for reducing photoaging, or oxidative stress or for prophylaxis against or reduction in the likelihood of the development of skin cancer, are also disclosed. The compositions and methods are also useful to treating other cancers.

Method to inhibit cell growth using oligonucleotides

Methods to control, or manipulate, melanocyte and keratinocyte cell death are disclosed. In particular, a method of preventing epidermal melanocyte cell loss due to injury in a vertebrate is disclosed. Also disclosed is a method of inducing hair growth in a vertebrate, a method of inducing hair color in a vertebrate, a method of inducing skin color in a vertebrate, a method of treating baldness in an individual, and a method of treating alopecia areata in an individual.

Inhibition of apoptosis in keratinocytes by a ligand of p75 nerve growth factor receptor

Methods of treatment or prevention of hyperproliferative diseases or pre-cancerous conditions affecting epithelial cells, such as psoriasis, vitiligo, atopic dermatitis, or hyperproliferative or UV-responsive dermatoses, hyperproliferative or allergically mediated diseases of other epithelia and methods for reducing photoaging, or oxidative stress or for prophylaxis against or reduction in the likelihood of the development of skin cancer, are disclosed.

Use of locally applied DNA fragments

Described are methods for treating hyperproliferative disorders, including cancers, by administering to the affected mammal (e.g., human) an effective amount of a composition comprising pTT or a composition comprising one or more oligonucleotides which share at least 50% nucleotide sequence identity with the human telomere overhang repeat. Methods of treatment or prevention of hyperproliferative diseases or pre-cancerous conditions affecting epithelial cells, such as psoriasis, atopic dermatitis, or hyperproliferative or UV-responsive dermatoses, hyperproliferative diseases of other epithelia and methods for reducing photoaging, or oxidative stress or for prophylaxis against or reduction in the likelihood of the development of skin cancer, are also disclosed.

Methods of inducing hair growth and coloration

Methods for evaluating the risk of an individual to develop Alzheimer's disease using cultured neural crest-derived melanocytes are described. Also described are methods of therapy for Alzheimer's disease using peptides that bind to the neurotrophin receptor (p75 ) and competitively inhibit the binding of &bgr;-amyloid to the p75 .

Identifying substances using cells that express p75NTR

Methods of inhibiting &bgr;-amyloid-mediated activation of the p75 nerve growth factor receptor of a cell that expresses the p75 nerve growth factor receptor are provided. Methods of inhibiting the binding of &bgr;-amyloid protein and &bgr;-amyloid peptides to the p75 nerve growth factor receptor, and methods of inhibiting &bgr;-amyloid-mediated apoptosis of neural crest-derived cells are provided. The methods comprise contacting the cell with a substance, comprising, for example, the amino acid sequence lysine-glycine-lysine (KGK) or lysine-glycine-alanine (KGA), wherein the substance binds to the p75 nerve growth factor receptor, resulting in the inhibition of &bgr;-amyloid protein or &bgr;-amyloid peptide binding to and/or activation of the p75 nerve growth factor receptor, or wherein the substance inhibits &bgr;-amyloid protein or &bgr;-amyloid peptide mediated apoptosis of the cell which expresses the p75 nerve growth factor receptor.

Inhibition of &bgr;-amyloid binding to the p75 nerve growth factor receptor

Methods of treatment or prevention of hyperproliferative diseases or pre-cancerous conditions affecting epithelial cells, such as psoriasis, vitiligo, atopic dermatitis, or hyperproliferative or UV-responsive dermatoses, hyperproliferative or allergically mediated diseases of other epithelia and methods for reducing photoaging or for prophylaxis against or reduction in the likelihood of the development of skin cancer, are disclosed.

A method for maintaining hair growth and coloration in humans by using neurotrophin ligands to prevent p75 nerve growth factor (NGF) receptor mediated apoptosis in melanocytes and keratinocytes is described.

Methods are described whereby vertebrate skin, hair, wool or fur may be lightened, or darkened, in color by administration of a substance, e.g., peptide, antibody, antibody fragment or DNA sequence encoding a peptide, that modulates the protein kinase C-beta-mediated activation of tyrosinase, the rate-limiting enzyme in melanogenesis.

Methods of modulating melanin synthesis

Methods of treatment or prevention of hyperproliferative diseases or pre-cancerous conditions affecting epithelial cells, such as psoriasis, vitiligo, atopic dermatitis, or hyperproliferative or UV-induced dermatoses, and methods for reducing photoaging or for prophylaxis against or reduction in the likelihood of the development of skin cancer, are disclosed. The methods comprise administering to the cells of interest an effective amount of DNA fragments, either single- or double-stranded, or a mixture of both single- and double-stranded fragments, or deoxynucleotides, dinucleotides, or dinucleotide dimers. The DNA fragments, deoxynucleotides, dinucleotides, or dinucleotide dimers can be administered in an appropriate vehicle, such as a liposomal preparation or propylene glycol. Preparations useful in the present methods are additionally disclosed. The preparations comprise DNA fragments, either single- or double-stranded, or a mixture of both single- and double-stranded fragments, or deoxynucleotides, dinucleotides, or dinucleotide dimers, and an appropriate delivery vehicle, such as liposomes or propylene glycol.

A method for inducing melanin synthesis in melanocytes, thereby increasing the melanin content of melanocytes and, thus, increasing pigmentation, melanocytes with increased melanin content produced by these methods, and uses thereof.

Methods for increasing melanin content in melanocytes using

Methods for enhancing melanin synthesis in melanocytes, thereby increasing the melanin content of melanocytes with subsequent transfer of the melanic pigments to keratinocytes resulting in increased pigmentation of vertebrate skin and hair; melanocytes with increased melanin content produced by these methods; and uses thereof are disclosed.

Methods for enhancing melanin synthesis in melanocytes using

A method of stimulating pigment production in mammalian skin, as well as protecting mammalian skin against ultraviolet damage, is disclosed. Also disclosed is a method of stimulating pigment production in mammalian cells, a method of stimulating melanogenesis in mammalian melanocytes, and a culture medium for stimulating melanin production. Preparations useful in the present methods are additionally disclosed. The methods comprise administering to the epidermis or to the cells DNA fragments, either single- or double-stranded, or a mixture of both, or deoxynucleotides, dinucleotides, or dinucleotide dimers, in an appropriate vehicle, such as a liposomal preparation or propylene glycol. The preparations include DNA fragments, deoxynucleotides, dinucleotides, or dinucleotide dimers and an appropriate delivery vehicle, such as liposomes or a propylene glycol. The DNA fragments, deoxynucleotides, or dinucleotides used in the methods or in the preparations can be ultraviolet-irradiated. The preparations are sunlight-independent tanning or melanogenesis-stimulating agent.

Stimulation of tanning by DNA fragments or single-stranded DNA

A method of increasing pigmentation in mammalian skin, as well as protecting mammalian skin against ultraviolet damage, is disclosed. Also disclosed is a method of increasing pigmentation in mammalian cells, as well as a method of enhancing melanin production in mammalian melanocytes. A preparation useful in the present methods is additionally disclosed. The methods comprise administering to the epidermis or to the cells DNA fragments, either single- or double-stranded, or a mixture of both, or deoxynucleotides, in a liposomal preparation or other appropriate vehicle. The preparation includes DNA fragments or deoxynucleotides and an appropriate delivery vehicle, such as liposomes.

Growing community of inventors

Boston, MA, United States of America

Barbara A Gilchrest