title: Transfer of the AQP1 cDNA for the correction of radiation-induced salivary hypofunction.
abstract: The treatment of most patients with head and neck cancer includes ionizing radiation (IR). Salivary glands in the IR field suffer significant and irreversible damage, leading to considerable morbidity. Previously, we reported that adenoviral (Ad)-mediated transfer of the human aquaporin-1 (hAQP1) cDNA to rat [C. Delporte, B.C. O'Connell, X. He, H.E. Lancaster, A.C. O'Connell, P. Agre, B.J. Baum, Increased fluid secretion after adenoviral-mediated transfer of the aquaporin-1 cDNA to irradiated rat salivary glands. Proc. Natl. Acad. Sci. U S A. 94 (1997) 3268-3273] and miniature pig [Z. Shan, J. Li, C. Zheng, X. Liu, Z. Fan, C. Zhang, C.M. Goldsmith, R.B. Wellner, B.J Baum, S. Wang. Increased fluid secretion after adenoviral-mediated transfer of the human aquaporin-1 cDNA to irradiated miniature pig parotid glands. Mol. Ther. 11 (2005) 444-451] salivary glands approximately 16 weeks following IR resulted in a dose-dependent increase in salivary flow to > or =80% control levels on day 3. A control Ad vector was without any significant effect on salivary flow. Additionally, after administration of Ad vectors to salivary glands, no significant lasting effects were observed in multiple measured clinical chemistry and hematology values. Taken together, the findings show that localized delivery of AdhAQP1 to IR-damaged salivary glands is useful in transiently increasing salivary secretion in both small and large animal models, without significant general adverse events. Based on these results, we are developing a clinical trial to test if the hAQP1 cDNA transfer strategy will be clinically effective in restoring salivary flow in patients with IR-induced parotid hypofunction.
authors.affiliation: Gene Therapy and Therapeutics Branch, Bethesda, MD 20892-1190, USA. bbaum@dir.nidcr.nih.gov
authors.forename: Bruce J
authors.initials: BJ
authors.lastname: Baum
authors.forename: Changyu
authors.initials: C
authors.lastname: Zheng
authors.forename: Ana P
authors.initials: AP
authors.lastname: Cotrim
authors.forename: Corinne M
authors.initials: CM
authors.lastname: Goldsmith
authors.forename: Jane C
authors.initials: JC
authors.lastname: Atkinson
authors.forename: Jaime S
authors.initials: JS
authors.lastname: Brahim
authors.forename: John A
authors.initials: JA
authors.lastname: Chiorini
authors.forename: Antonis
authors.initials: A
authors.lastname: Voutetakis
authors.forename: Rose Anne
authors.initials: RA
authors.lastname: Leakan
authors.forename: Carter
authors.initials: C
authors.lastname: Van Waes
authors.forename: James B
authors.initials: JB
authors.lastname: Mitchell
authors.forename: Christine
authors.initials: C
authors.lastname: Delporte
authors.forename: Songlin
authors.initials: S
authors.lastname: Wang
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Kaminsky
authors.forename: Gabor G
authors.initials: GG
authors.lastname: Illei
mesh_terms: D000818:Animals; D051398:Aquaporin 1 / Q000235:genetics* / Q000378:metabolism; D018076:DNA, Complementary / Q000235:genetics*; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors; D006258:Head and Neck Neoplasms / Q000532:radiotherapy*; D006801:Humans; D010306:Parotid Gland / Q000503:physiopathology / Q000528:radiation effects; D011833:Radiation Injuries, Experimental / Q000628:therapy*; D051381:Rats; D012466:Salivary Gland Diseases / Q000628:therapy*; D012469:Salivary Glands / Q000503:physiopathology / Q000528:radiation effects*; D013552:Swine; D013556:Swine, Miniature
chemical_list: D018076:DNA, Complementary; D051398:Aquaporin 1