Transfer of the AQP1 cDNA for the correction of radiation-induced salivary hypofunction.
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.
Baum
Bruce J
BJ
Gene Therapy and Therapeutics Branch, Bethesda, MD 20892-1190, USA. bbaum@dir.nidcr.nih.gov
Zheng
Changyu
C
Cotrim
Ana P
AP
Goldsmith
Corinne M
CM
Atkinson
Jane C
JC
Brahim
Jaime S
JS
Chiorini
John A
JA
Voutetakis
Antonis
A
Leakan
Rose Anne
RA
Van Waes
Carter
C
Mitchell
James B
JB
Delporte
Christine
C
Wang
Songlin
S
Kaminsky
Stephen M
SM
Illei
Gabor G
GG
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
D018076:DNA, Complementary; D051398:Aquaporin 1