Introduction:
Short chain fatty acids (SCFAs) are saturated aliphatic acids consisting of one polar carboxylic acid moiety and hydrophobic hydrocarbon cahin. Among these, acetate (C2), propionate (C3) and butyrate (C4) are the cmost common and well studied molecules. SCFas are fatty acids with aliphatic tails shorter than aliphatic tails of long chain fatty acids. (WO2024/151503)
SCFAs can be deritized to provide a slat or ester thereof, for example, salts and esters of fatty acids include sodium butyrate and argine butyrate.
Examples of Short Chain Fatty Acids (SCFAs):
Examples of SCFA include acetic acid, butyric acid (BA), C3-C12 fatty acids, C3-C10 fatty acids, C3-C8 fatty acids, methoxyacetic acid, valproic acid (VPA), propionic acid, 3-methoxypropionic acid, ethoxyacetic acid, formic acid, isobutyric acid, tributyrin, N-acetylbutyrate (and other forms of butyrate, e.g., phenylbutyrate, isobutyrate, pivaloyloxymethl butryrate, monoacetone glucose 3-butyrate0, solvaleric acid, valeric acid, isocaproin acid, carpoic acid, lactic acid, succinic acid, pyruvic acid, octanoic acid, dodecanoic acid, (4R)-4-hydroxypentanoic acid, 2-ethylhydracrylic acid, 2-hydroxy-3-methylpentanoate, 2-hydroxy-3-methylpentanoic acid, 2-methylbut-2-enoic acid, 2-oxobutanoic acid, 3-hydroxypentanoic acid, 3-methylbut-2-enoic acid, butenoic acid, methylbutyric acid, demthylbutyric acid, pentadienoic acid, pentenoic acid, pivalic acid, propynoic acid. (WO2024/151503)
Treatment of Diseases with SCFAs:
(WO2024/151503) disclsoses using SCFAs in the treatment of askin disorders such as psoriasis, systemic lupus erythematosis (SLE) rash, sckeroderma (systemic sclerosis), diabetes reated skin conditions, rheumatoid arthitis and associated skin rashes (rheumatoic vasculitis), melanoma, vitiligo, eczema (atopic dermatitis), dyshidrotic exzema, rosacea, hives, impetigo, cellulitis, contact dermatitis, canker sores, acne, Lichen planus, actinic keratosis, ichthyosis vulgaris, dermatomyositis, and pemphigoid. in some embodiemtns, the SCFA includes one or more of formic acid, acetic acid, propionic acid, isobutyric acid, butyric acid, tributyrin, N-acetylbutyrate (and other forms of butyrate), isovaleric acid, valeric acid, isocaproic acid, caproic acid, lactic acid, succinic acid, pyruvic acid, octanoic acid and dodecanoic acid. In some embodimetns a seocnd compound is included for the therapeutic of skin disorders such as a PDE4 inhibitor, an anti-infoammatory compound, a disease modifying anithermatic drug (DMARD), a immunosuppressant, a biologic agetna dna Cox-2 inhibitor. Examples of PDE4 inhibitors include Apremilast, orflumilast, Crisaborole and HFP034. In some embodimetns, the methods include adminsitering at least one sCFA and one or more of vitamin D3, vitamin E and magensium.
Psoriasis: is a chronic autoimmune disorder affecting the skin. The clinical appearance of psoriasis results from a dysregulated interaction between immune cells (e.g., DCs and T cells) and keratinocytes leading to inflammatory process which drive the disease. The skin inflammation causes a rapid keratinocyte proliferation ending up in scaling of skin’s surface, which shows a common phenotype of dry, raised, red skin lesions (plaques) covered with silvery scales. Examples of psoriasis include plaque psoriasis, guttate psoriasis, inverse psoriasis, postular psoriasis, psoriasis vulgaris, seborrheic psyoriasis erythrodermic psoriasis, nail psoriasis, and psoriatic arthtritic. (WO2024/151503)
(WO2024/151503) disclsoes methods of using SCFAs to treat psoriasis. Various skin models were used such as InflammaSkin psoriasis model which is an ex vivo psoriasis skin model with a T-cell driven inflammation featuring the Th1/Th17 phenotype and NativeSkin human skin model to evaluate the response of real human skin.