Topical RT1640 treatment effectively reverses gray hair and stem cell loss in a mouse model of radiation-induced canities

Pigment Cell Melanoma Res. 2021 Jan;34(1):89-100. doi: 10.1111/pcmr.12913. Epub 2020 Jul 24.


Gray hair is a visible sign of tissue degeneration during aging. Graying is attributed to dysfunction of melanocyte stem cells (McSCs) that results in depletion of their melanin-producing progeny. This non-lethal phenotype makes the hair follicle and its pigment system an attractive model for investigating mechanisms that contribute to tissue aging and therapeutic strategies to combat this process. One potential combination therapeutic is RT1640, which is comprised of two drugs that are known to stimulate hair growth (cyclosporine A [CsA] and minoxidil), along with RT175, a non-immunosuppressive immunophilin ligand that is implicated in tissue regeneration. Using the ionizing radiation-induced acute mouse model of hair graying, we demonstrate that RT1640, over CsA alone, promotes regeneration of the hair pigment system during and following treatment. In non-irradiated mice, RT1640 is also physiologically active and successfully speeds hair growth and expands the McSC pool. It appears that this effect relies on the combined activities of the three drugs within RT1640 to simultaneously activate hair growth and McSCs as RT175 alone was insufficient to induce hair cycling in vivo, yet sufficient to drive the upregulation of the melanogenic program in vitro. This study sets the stage for further investigation into RT1640 and its components in McSC biology and, ultimately, melanocyte hypopigmentary disorders associated with disease and aging.

Keywords: FKBP; RT1640; hair follicle; hair graying; immunophilin; ionizing radiation; melanocyte; stem cell; tissue rejuvenation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Topical
  • Animals
  • Cyclosporine / administration & dosage*
  • Dermatologic Agents / administration & dosage
  • Disease Models, Animal
  • Drug Combinations
  • Female
  • Gamma Rays / adverse effects*
  • Hair Color / drug effects*
  • Hair Color / radiation effects
  • Hair Diseases / drug therapy*
  • Hair Diseases / etiology
  • Hair Diseases / pathology
  • Male
  • Melanins / metabolism
  • Melanocytes / drug effects
  • Melanocytes / radiation effects
  • Mice
  • Mice, Inbred C57BL
  • Minoxidil / administration & dosage*
  • Pigmentation Disorders / drug therapy*
  • Pigmentation Disorders / etiology
  • Pigmentation Disorders / pathology
  • Stem Cells / drug effects*
  • Stem Cells / radiation effects
  • Vasodilator Agents / administration & dosage


  • Dermatologic Agents
  • Drug Combinations
  • Melanins
  • Vasodilator Agents
  • Minoxidil
  • Cyclosporine