title: Treatment and prevention of chemotherapy-induced alopecia with PTH-CBD, a collagen-targeted parathyroid hormone analog, in a non-depilated mouse model.
abstract: Alopecia is a psychologically devastating complication of chemotherapy for which there is currently no effective therapy. PTH-CBD is a collagen-targeted parathyroid hormone analog that has shown promise as a therapy for alopecia disorders. This study compared the efficacy of prophylactic versus therapeutic administration of PTH-CBD in chemotherapy-induced alopecia using a mouse model that mimics the cyclic chemotherapy dosing used clinically. C57BL/6J mice were treated with a single subcutaneous injection of PTH-CBD (320 mcg/kg) or vehicle control before or after hair loss developing from three courses of cyclophosphamide chemotherapy (50-150 mg/kg/week). Mice receiving chemotherapy alone developed hair loss and depigmentation over 6-12 months. Mice pretreated with PTH-CBD did not develop these changes and maintained a normal-appearing coat. Mice treated with PTH-CBD after development of hair loss showed a partial recovery. Observations of hair loss were confirmed quantitatively by gray scale analysis. Histological examination showed that in mice receiving chemotherapy alone, there were small, dystrophic hair follicles mostly in the catagen phase. Mice receiving PTH-CBD before chemotherapy showed a mix of normal-appearing telogen and anagen hair follicles with no evidence of dystrophy. Mice receiving PTH-CBD therapy after chemotherapy showed intermediate histological features. PTH-CBD was effective in both the prevention and the treatment of chemotherapy-induced alopecia in mice, but pretreatment appears to result in a better cosmetic outcome. PTH-CBD shows promise as an agent in the prevention of this complication of chemotherapy and improving the quality of life for cancer patients.
authors.affiliation: aPediatric Endocrinology, Children's Hospital at Montefiore and Albert Einstein College of Medicine, Bronx, New York bDepartment of Chemistry and Biochemistry, University of Arkansas, Fayetteville, Arkansas, USA cDepartment of Bacteriology, Okayama University Graduate School of Medicine, Okayama, Japan.
authors.forename: Ranjitha
authors.initials: R
authors.lastname: Katikaneni
authors.forename: Tulasi
authors.initials: T
authors.lastname: Ponnapakkam
authors.forename: Osamu
authors.initials: O
authors.lastname: Matsushita
authors.forename: Joshua
authors.initials: J
authors.lastname: Sakon
authors.forename: Robert
authors.initials: R
authors.lastname: Gensure
mesh_terms: D000505:Alopecia / Q000139:chemically induced / Q000188:drug therapy* / Q000517:prevention & control; D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects*; D001426:Bacterial Proteins / Q000235:genetics; D003094:Collagen / Q000378:metabolism*; D017364:Collagenases / Q000235:genetics; D003520:Cyclophosphamide / Q000009:adverse effects*; D018859:Hair Follicle / Q000187:drug effects / Q000254:growth & development; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D058990:Molecular Targeted Therapy; D010281:Parathyroid Hormone / Q000819:agonists / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000627:therapeutic use
chemical_list: D018906:Antineoplastic Agents, Alkylating; D001426:Bacterial Proteins; D010281:Parathyroid Hormone; D011993:Recombinant Fusion Proteins; D003520:Cyclophosphamide; D003094:Collagen; C118796:ColH protein, Clostridium histolyticum; D017364:Collagenases
references.citation: FASEB J. 1994 Feb;8(2):226-30
references.pmid: 8119493
references.citation: Support Care Cancer. 1997 Mar;5(2):136-8
references.pmid: 9069614
references.citation: J Am Acad Dermatol. 1996 Jul;35(1):74-8
references.pmid: 8682968
references.citation: Cancer. 1984 Jul 1;54(1):34-7
references.pmid: 6372986
references.citation: Pharm Res. 2006 Nov;23(11):2505-14
references.pmid: 16972183
references.citation: Cancer Res. 1996 Oct 1;56(19):4438-43
references.pmid: 8813138
references.citation: Cell. 2001 May 18;105(4):533-45
references.pmid: 11371349
references.citation: Cancer Nurs. 1984 Jun;7(3):221-8
references.pmid: 6372990
references.citation: N Engl J Med. 1978 May 25;298(21):1204-5
references.pmid: 651958
references.citation: Life Sci. 2008 Jan 16;82(3-4):218-25
references.pmid: 18164732
references.citation: J Invest Dermatol. 2009 Feb;129(2):506-9
references.pmid: 18704109
references.citation: Ann Oncol. 2006 Feb;17(2):350
references.pmid: 16166175
references.citation: Nutrition. 1996 Jun;12(6):448-9
references.pmid: 8875542
references.citation: Lab Invest. 1996 Oct;75(4):601-9
references.pmid: 8874390
references.citation: Ann Oncol. 2005 Mar;16(3):352-8
references.pmid: 15642703
references.citation: Int J Cancer. 2012 Sep 1;131(5):E813-21
references.pmid: 22130912
references.citation: Cancer Pract. 2001 Nov-Dec;9(6):283-9
references.pmid: 11879330
references.citation: Br Med J. 1966 Nov 5;2(5522):1138
references.pmid: 5920683
references.citation: Cancer Nurs. 1988 Jun;11(3):170-3
references.pmid: 3401852
references.citation: J Invest Dermatol. 1998 Oct;111(4):598-604
references.pmid: 9764839
references.citation: Calcif Tissue Int. 2012 Sep;91(3):196-203
references.pmid: 22806683
references.citation: J Endocrinol Invest. 2011 Dec;34(11):e392-7
references.pmid: 21750397
references.citation: J Dermatol Sci. 2001 Sep;27(1):7-13
references.pmid: 11457638
references.citation: Tumori. 2010 Mar-Apr;96(2):271-5
references.pmid: 20572585
references.citation: Skin Therapy Lett. 2010 Jul-Aug;15(7):5-7
references.pmid: 20700552
references.citation: J Invest Dermatol. 2013 Jan;133(1):7-9
references.pmid: 23299447
references.citation: Australas J Dermatol. 2000 May;41(2):106-8
references.pmid: 10812705
references.citation: Cell Stress Chaperones. 2008 Spring;13(1):31-8
references.pmid: 18347939
references.citation: J Invest Dermatol. 2001 Aug;117(2):173-8
references.pmid: 11511291
references.citation: South Med J. 1993 May;86(5):489-96
references.pmid: 8488392
references.citation: Eur J Cancer. 2000 Apr;36(6):766-71
references.pmid: 10762750
references.citation: Nat Med. 2005 Dec;11(12):1351-4
references.pmid: 16288281
references.citation: Semin Cutan Med Surg. 2009 Mar;28(1):11-4
references.pmid: 19341937
references.citation: J Natl Cancer Inst. 2001 Dec 19;93(24):1858-64
references.pmid: 11752010
references.citation: J Endocrinol. 2001 Dec;171(3):403-16
references.pmid: 11739006
references.citation: Cancer Nurs. 1984 Dec;7(6):499-503
references.pmid: 6568869
references.citation: J Invest Dermatol. 2005 Jul;125(1):42-51
references.pmid: 15982301
references.citation: Differentiation. 2004 Dec;72(9-10):548-57
references.pmid: 15617565
references.citation: Neth J Med. 1990 Dec;37(5-6):231-5
references.pmid: 2074916
references.citation: Am J Pathol. 1994 Apr;144(4):719-34
references.pmid: 8160773