Treatment of autoimmune diseases
Inventors
Assignees
Publication Number
US-11680273-B2
Publication Date
2023-06-20
Expiration Date
2032-09-21
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Abstract
Compositions can be used to stimulate growth of a hair shaft from a hair follicle. These compositions can include methylated polynucleotides useful in treatment of autoimmune diseases or conditions, including those, such as alopecia areata, that result in hair loss.
Core Innovation
The invention relates to compositions and methods for stimulating hair growth or treating hair loss caused by autoimmune conditions, particularly alopecia areata. It specifically utilizes polynucleotides encoding a pro-apoptotic protein, such as Bax or its functional fragments, with a defined level of methylation at CpG dinucleotides. The methylation state of these polynucleotides is set to be about 2-fold to about 4-fold higher than the average methylation level found in wild type Escherichia coli genomes, or within a range of about 30% to about 60% of CpG dinucleotides methylated.
The problem addressed is the lack of effective therapies for autoimmune-related hair loss, such as alopecia areata, where the immune system attacks hair follicles resulting in hair loss. Conventional treatments for alopecia areata and related hair loss conditions are either ineffective or have limited efficacy, especially for types suspected to be immune mediated.
By administering these methylated polynucleotide compositions intradermally to the site of hair loss or adjacent areas, the immune system can be modulated to induce immune tolerance at the site of inflammation, thereby reducing the abnormal autoimmune response and stimulating hair shaft growth. The document also describes methods for preparing these methylated polynucleotides using bacteria engineered to express CpG methylase from a stably integrated chromosomal gene under the control of a constitutive promoter.
Claims Coverage
The patent contains two independent claims, each outlining the main inventive features for methods of stimulating hair growth and treating hair loss associated with autoimmune disease using methylated Bax-encoding polynucleotides.
Method of stimulating hair growth by administration of a methylated Bax polynucleotide composition
A method is provided for stimulating hair growth in a human subject suffering hair loss from an autoimmune disorder by administering an effective amount of a composition comprising a polynucleotide that encodes a Bax protein or a Bax pro-apoptotic functional fragment thereof. - The polynucleotide is: - Operably linked to an expression control element. - Methylated at CpG dinucleotides at a level about 2-fold to about 4-fold higher compared to the average methylation level in a wild type Escherichia coli genome. - The administration is intradermally at or near the site of hair loss, or to a site where hair is present, or combinations thereof.
Method of stimulating hair shaft growth using a polynucleotide with defined CpG methylation
A method of stimulating the growth of a hair shaft from a hair follicle in a human subject with an autoimmune disorder by administering an effective amount of a polynucleotide encoding Bax protein or a Bax pro-apoptotic functional fragment, operably linked to an expression control element. - About 30% to about 60% of the CpG dinucleotides of the polynucleotide are methylated. - The polynucleotide is administered intradermally directly to the site of hair loss, directly adjacent, to a site where hair is present, or combinations thereof.
In summary, the inventive features cover the specific use of Bax-encoding polynucleotides with defined levels of CpG methylation for intradermal administration to treat autoimmune-related hair loss and stimulate hair regrowth.
Stated Advantages
The invention enables the treatment of hair loss resulting from autoimmune disease, particularly in cases for which no highly effective therapies exist, such as alopecia areata.
By using defined methylation levels in polynucleotide compositions, the invention allows modulation of the immune response, promoting immune tolerance at the site of autoimmune attack.
Administration of methylated plasmid DNA at controlled CpG levels can reduce adverse immune responses and increase the duration and efficacy of gene expression for therapeutic benefit.
Documented Applications
Treatment of hair loss (including alopecia areata) caused by autoimmune disease by stimulating hair growth.
Stimulating growth of a hair shaft from a hair follicle in subjects afflicted by autoimmune disorders.
Treatment of white hair, vellus hair formation, or as an agent for inhibiting seborrheic scalp or dandruff occurrence.
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