Zeitschrift für klinische und experimentelle Dermatologieforschung
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Treatment of Alopecia Areata in Mice by Stimulating the Hair Follicles Using Parathyroid Hormone Agonists Linked to a Collagen Binding Domain

Ranjitha Katikaneni, Tulasi Ponnapakkam, Rohan Gulati, Andrew A. Seymour and Robert Gensure

Alopecia Areata is a patchy hair loss from autoimmune-mediated destruction of hair follicles, for which there is no adequate therapy. PTH-CBD is a fusion protein of parathyroid hormone and a bacterial collagen-binding domain, providing targeted delivery of a hair cycle stimulator to skin and promoting hair growth.

Objectives: We tested the effects of PTH-CBD on hair growth in an established animal model for alopecia areata, the C3H/HeJ engrafted mouse.

Methods: C3H/HeJ engrafted mice (Jackson Laboratories, Bar Harbor, ME) were treated subcutaneously for 8 weeks with either vehicle or different doses of PTH-CBD (320 mcg/kg x1, 1000 mcg/kg x1 or 1000 mcg/kg/wk).

Results: Vehicle animals showed progressive hair loss, as expected. In PTH-CBD treated animals, grey scale quantification showed a greater proportion of PTH-CBD treated animals without significant hair loss at the end of the 2 month period (18/22 PTH-CBD vs. 4/11 vehicle), with no observed differences between the different PTH-CBD treatment regimens. Histological examination revealed no change in CD8+ cells, but there was a marked increases in the number of anagen VI hair follicles in PTH-CBD treated animals. There were also increased levels of betacatenin, a known initiator of the hair cycle, observed around the bulge region of hair follicles.

Conclusions: C3H/HeJ engrafted animals treated with PTH-CBD showed rapid and persistent improvements in hair growth in the majority of tested animals. There were marked increases in anagen hair follicles despite an ongoing immune reaction. Increased beta catenin levels suggest that PTH-CBD stimulates hair growth by activating the Wnt pathway.