by screening using a high-throughput evaluation system relating to the promotion of the extracellular secretion of trimers of the causative proteins COL4A3/A4/A5, which decreased in the renal tissue of patients with Alport syndrome (AS), it was found that cyclosporin A has an effect of promoting extracellular secretion of trimers of type-IV collagen. From further studies, it was found that Alisporivir and NIM258, which do not inhibit calcineurin, also have an action to promote extracellular secretion of type-IV collagen. Furthermore, the present inventors have found that these actions are based on the cyclophilin D inhibitory mechanism, and have found a radical therapeutic agent for AS by inhibition of cyclophilin D. The present invention provides a composition and an AS therapeutic/prophylactic drug, which contain a cyclophilin D inhibitor as an active ingredient, for promoting the secretion of collagen trimers in cells having a mutated type-IV collagen gene.

A compound of the Formula (I) is disclosed:

##STR00001##

or pharmaceutically acceptable salt thereof, wherein the symbols are as defined in the specification. Also described are a pharmaceutical composition comprising the same and a method for treating or preventing viral infections, inflammation, dry eye, central nervous disorders, cardiovascular diseases, cancer, obesity, diabetes, muscular dystrophy, lung, and liver, and kidney diseases, and hair loss using the same.

A compound of the Formula (I) is disclosed:

##STR00001##

or pharmaceutically acceptable salt thereof, wherein the symbols are as defined in the specification. Also described are a pharmaceutical composition comprising the same and a method for treating or preventing viral infections, inflammation, dry eye, central nervous disorders, cardiovascular diseases, cancer, obesity, diabetes, muscular dystrophy, lung, and liver, and kidney diseases, and hair loss using the same.

The present invention pertains to: the provision of a method for promoting skin wound healing and a composition to be used for promoting skin wound healing; the provision of a method useful for preventing or ameliorating ulcers and bedsores or a composition therefor; the provision of a method for preventing skin aging and a composition to be used for preventing skin aging; the provision of a composition useful for preventing or ameliorating skin damage caused by an anticancer agent; and, furthermore, the provision of a method for enhancing the regeneration ability of epidermal stem cells and a composition for enhancing the regeneration ability of epidermal stem cells. More specifically, use of a composition, said composition being characterized by comprising, as an active ingredient, a substance selected from the group consisting of a substance which induces or maintains the expression of COL17A1 in cells, a substance which inhibits the degradation of COL17A1 in cells, a substance which promotes the competitive amplification ability of epidermal stem cells, a substance which suppresses genomic stress or oxidative stress in cells and a substance which prevents DNA damage in cells, enables the promotion of skin wound healing, protection from an anticancer agent and prevention of skin aging. Thus, the regeneration ability of epidermal stem cells can be enhanced.

Embodiments disclosed herein relate to compositions and methods for inducing transplantation tolerance using immunomodulation agents. In certain embodiments compositions and methods disclosed herein, concern administering a composition including, but not limited to, anti-CD3 immunotoxin and administering a composition including, but not limited to, peripheral blood cells obtained from a donor of an organ, tissue or cells to be transplanted. In some embodiments, compositions and methods disclosed here can be used for modulating B- and/or T-cell-mediated immunity and/or rejection by reducing or eliminating anti-donor antibody production. Other embodiments concern modulating T-cell production in a subject preparing for, undergoing organ, tissue or cellular transplantation; or having or expected of developing GvHD for reducing the risk of, preventing or treating rejection or GvHD. In certain embodiments, combination compositions of anti-CD3 immunotoxin and peripheral blood cells from a donor are contemplated.

Embodiments disclosed herein relate to compositions and methods for inducing transplantation tolerance using immunomodulation agents. In certain embodiments compositions and methods disclosed herein, concern administering a composition including, but not limited to, anti-CD3 immunotoxin and administering a composition including, but not limited to, peripheral blood cells obtained from a donor of an organ, tissue or cells to be transplanted. In some embodiments, compositions and methods disclosed here can be used for modulating B- and/or T-cell-mediated immunity and/or rejection by reducing or eliminating anti-donor antibody production. Other embodiments concern modulating T-cell production in a subject preparing for, undergoing organ, tissue or cellular transplantation; or having or expected of developing GvHD for reducing the risk of, preventing or treating rejection or GvHD. In certain embodiments, combination compositions of anti-CD3 immunotoxin and peripheral blood cells from a donor are contemplated.

The present invention relates to a composition comprising cyclosporine A (CsA) for use in the prevention of bronchiolitis obliterans syndrome (BOS) in a double lung transplanted patient, or for the treatment of BOS or for the prevention or delay of the progression of BOS in a double lung transplanted patient being diagnosed with BOS, wherein the composition is administered to said patient by inhalation of said composition in aerosolized form comprising a therapeutically effective dose of cyclosporine A.

The present invention relates to a composition comprising cyclosporine A (CsA) for use in the prevention of bronchiolitis obliterans syndrome (BOS) in a double lung transplanted patient, or for the treatment of BOS or for the prevention or delay of the progression of BOS in a double lung transplanted patient being diagnosed with BOS, wherein the composition is administered to said patient by inhalation of said composition in aerosolized form comprising a therapeutically effective dose of cyclosporine A.

The present invention relates to S1P receptor modulators, preferably mocravimod, for use in treating patients suffering from a hematological malignancy, e.g., acute myeloid leukemia (AML), and who have undergone allogeneic hematopoietic stem cell transplantation (HSCT). The invention relates in particular to methods of treating AML in subjects undergoing HSCT, wherein said method comprises daily administering an efficient amount of S1P receptor modulator, preferably mocravimod, to said subject in need thereof, for at least 6 months, preferably at least 12 months.

The present invention relates to S1P receptor modulators, preferably mocravimod, for use in treating patients suffering from a hematological malignancy, e.g., acute myeloid leukemia (AML), and who have undergone allogeneic hematopoietic stem cell transplantation (HSCT). The invention relates in particular to methods of treating AML in subjects undergoing HSCT, wherein said method comprises daily administering an efficient amount of S1P receptor modulator, preferably mocravimod, to said subject in need thereof, for at least 6 months, preferably at least 12 months.