Parathyroid hormone linked to a collagen binding domain promotes hair growth in a mouse model of chemotherapy-induced alopecia in a dose-dependent manner.
Chemotherapy-induced alopecia is a major source of psychological stress in patients undergoing cancer chemotherapy, and it can influence treatment decisions. Although there is currently no therapy for alopecia, a fusion protein of parathyroid hormone and collagen binding domain (PTH-CBD) has shown promise in animal models. The aim of this study was to determine whether there are dose-dependent effects of PTH-CBD on chemotherapy-induced alopecia in a mouse model. C57BL/6J mice were waxed to synchronize hair follicles; treated on day 7 with vehicle or PTH-CBD (100, 320, and 1000 mcg/kg subcutaneous injection); and treated on day 9 with vehicle or cyclophosphamide (150 mg/kg intraperitoneally). Mice were photographed every 3-4 days and killed on day 63 for histological analysis. Photographs were quantified by gray scale analysis to assess hair content. Mice not receiving chemotherapy showed regrowth of hair 2 weeks after waxing and normal histology after 2 months. Mice receiving chemotherapy alone showed marked hair loss after chemotherapy, which was sustained for 10 days and was followed by rapid regrowth of a normal coat. Histological analysis revealed rapid cycling dystrophic anagen/catagen follicles. Animals receiving chemotherapy and PTH-CBD showed decreased hair loss and more rapid regrowth of hair than that seen with chemotherapy alone (increased hair growth by gray scale analysis, P<0.05), and the effects were dose dependent. Histologically, hair follicles in animals receiving the highest dose of PTH-CBD were in a quiescent phase, similar to that in mice that did not receive chemotherapy. Single-dose subcutaneous administration of PTH-CBD showed dose-dependent effects in minimizing hair loss and speeding up recovery from chemotherapy-induced alopecia.
aPediatric Endocrinology bDepartment of Pathology, Children's Hospital at Montefiore and Albert Einstein College of Medicine, Bronx, New York cDepartment of Chemistry and Biochemistry, University of Arkansas, Fayetteville, Arkansas, USA.
Ranjitha
R
Katikaneni
Tulasi
T
Ponnapakkam
Andrew
A
Seymour
Joshua
J
Sakon
Robert
R
Gensure
D000505:Alopecia / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects*; D003520:Cyclophosphamide / Q000009:adverse effects; D004195:Disease Models, Animal; D005260:Female; D006197:Hair / Q000187:drug effects* / Q000503:physiopathology; D008810:Mice, Inbred C57BL; D011993:Recombinant Fusion Proteins / Q000494:pharmacology* / Q000627:therapeutic use
D000970:Antineoplastic Agents; C000591831:PTH-CBD fusion protein; D011993:Recombinant Fusion Proteins; D003520:Cyclophosphamide