Topics

2009/09/30

  • available-technologies
  • Biotechnology
  • Other

We found that cannabinoid agonists or vanilloid agonists can increase Serca2 gene expression and ATP2A2 calcium pump expression in human and mouse cultured keratinocytes and human epidermis in vivo. Additionally, we found that both cannabinoid receptor 1 (CB1) and cannabinoid receptor 2 (CB2) are expressed in human epidermal keratinocytes. We also found that several isoforms of TRPV, (TRPV1, 3, 4, 5, 6) vanilloid receptors are expressed in human epidermal keratinocytes.
These actions are useful for a prevention and/or a treatment for skin diseases induced by abnormality of calcium metabolism in epidermal keratinocyte such as Darier’s disease and also useful for a variety of skin diseases those are characterized by the hyperkeratosis and accelerated mitosis including psoriasis.

The present invention thus provides:
(1) A pharmaceutical agent for the prevention and/or treatment of a skin disease induced by accelerated keratinization, wherein the pharmaceutical agent comprises a substance selected from the group consisting of a cannabinoid agonist and a vanilloid agonist as an active ingredient.
(2) The pharmaceutical agent as described above, wherein the skin disease induced by accelerated keratinization is an inflammatory keratosis (non-hereditary) or a congenital keratoderma (hereditary).
(3) The pharmaceutical agent as described above, wherein the skin disease induced by accelerated keratinization is a congenital keratoderma induced by abnormality of calcium metabolism in epidermal keratinocyte.
(4) The pharmaceutical agent as described above, wherein the congenital keratoderma induced by abnormality of calcium metabolism in epidermal keratinocyte is Darier disease or Hailey-Hailey disease.
(5) The pharmaceutical agent as described above, which comprises a vanilloid agonist and a cannabinoid agonist as an active ingredient.

[Effect of the present invention]
-The pharmaceutical agent has actions that enhance Serca2 gene expression, increase expression level of ATP2A2 protein (calcium pump), which is encoded by Serca2 gene, and decrease intracellular calcium concentration. Therefore, the pharmaceutical agent enables to control an abnormally accelerated keratinization and to recover a normal keratinization.
-The pharmaceutical agent shows a very high efficiency for a skin disease induced by accelerated keratinization, such as an inflammatory keratosis (nonhereditary) or a congenital keratoderma (hereditary), preferably a hereditary skin disease induced by abnormality of calcium metabolism in epidermal keratinocyte such as Darier disease and Hailey-Hailey disease.
-The pharmaceutical agent could completely treat for intractable hereditary congenital keratoderma including Darier disease and Hailey-Hailey disease, of which therapeutic approach was conventionally only palliative care.

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