RESUMEN
UNLABELLED: Alopecia areata is a common disorder in which autoimmune destruction of hair follicles results in patchy hair loss. Currently there is no adequate therapy, although immune modulator therapies are currently in development. Parathyroid hormone (PTH) is a hair cycle stimulator which shows promise in treating various forms of alopecia, although its short half-life limits its clinical use. PTH-CBD is a PTH analog which binds collagen, prolonging retention in skin. We tested effects of PTH-CBD in C3H/HeJ-engrafted mice, the animal model for alopecia areata, on hair growth and found that a significant proportion of animals had reduced hair loss (PTH-CBD: 13/21, 62% vs. CONTROL: 3/10, 30%; P<0.01). Histological analysis showed no change in immune response, but there was increased number of anagen hair follicles and increased production of beta-catenin, a factor which initiates the anagen phase of the hair cycle. PTH-CBD thus shows promise as a therapy for alopecia areata, either alone or in conjunction with immune modulation therapy.
Asunto(s)
Alopecia Areata/tratamiento farmacológico , Folículo Piloso/efectos de los fármacos , Hormona Paratiroidea/agonistas , Proteínas Recombinantes de Fusión/uso terapéutico , Alopecia Areata/inmunología , Alopecia Areata/patología , Animales , Modelos Animales de Enfermedad , Cabello/crecimiento & desarrollo , Folículo Piloso/patología , Ratones , beta Catenina/metabolismoRESUMEN
Alopecia is a common form of hair loss which can occur in many different conditions, including male-pattern hair loss, polycystic ovarian syndrome, and alopecia areata. Alopecia can also occur as a side effect of chemotherapy in cancer patients. In this study, our goal was to develop a consistent and reliable method to quantify hair loss in mice, which will allow investigators to accurately assess and compare new therapeutic approaches for these various forms of alopecia. The method utilizes a standard gel imager to obtain and process images of mice, measuring the light absorption, which occurs in rough proportion to the amount of black (or gray) hair on the mouse. Data that has been quantified in this fashion can then be analyzed using standard statistical techniques (i.e., ANOVA, T-test). This methodology was tested in mouse models of chemotherapy-induced alopecia, alopecia areata and alopecia from waxing. In this report, the detailed protocol is presented for performing these measurements, including validation data from C57BL/6 and C3H/HeJ strains of mice. This new technique offers a number of advantages, including relative simplicity of application, reliance on equipment which is readily available in most research laboratories, and applying an objective, quantitative assessment which is more robust than subjective evaluations. Improvements in quantification of hair growth in mice will improve study of alopecia models and facilitate evaluation of promising new therapies in preclinical studies.
Asunto(s)
Alopecia/diagnóstico , Fotograbar/métodos , Alopecia/inducido químicamente , Alopecia Areata/diagnóstico , Animales , Cabello/efectos de los fármacos , Cabello/crecimiento & desarrollo , Ratones , Ratones Endogámicos C3H , Ratones Endogámicos C57BL , Reproducibilidad de los ResultadosRESUMEN
Alopecia areata is a common form of hair loss in which autoimmune-mediated destruction of hair follicles causes patchy hair loss, for which there is no adequate therapy. Parathyroid hormone (PTH) induces the hair cycle and promotes hair growth. PTH-CBD is a fusion protein of PTH and a bacterial collagen-binding domain (CBD), leading to targeted delivery to and retention in the skin collagen. We tested the effects of a single dose of PTH-CBD (low or high dose) on an animal model for alopecia areata, the C3H/HeJ engrafted mouse. In all the treated animals, there was a rapid (1-4 days) increase in hair growth, with sustained effects observed over a 2-month period (7/10 total treated mice<40% hair loss based on gray scale analysis, vs. 2/5 in vehicle control animals). Histological examination revealed massive stimulation of anagen VI hair follicles in treated animals despite an ongoing immune response. PTH-CBD thus shows promise as a therapy for alopecia areata, likely in conjunction with a mild immune suppressant, such as hydrocortisone cream.