Aquaporin-1 gene transfer to correct radiation-induced salivary hypofunction.
Irradiation damage to salivary glands is a common iatrogenic consequence of treatment for head and neck cancers. The subsequent lack of saliva production leads to many functional and quality-of-life problems for affected patients and there is no effective conventional therapy. To address this problem, we developed an in vivo gene therapy strategy involving viral vector-mediated transfer of the aquaporin-1 cDNA to irradiation-damaged glands and successfully tested it in two pre-clinical models (irradiated rats and miniature pigs), as well as demonstrated its safety in a large toxicology and biodistribution study. Thereafter, a clinical research protocol was developed that has received approval from all required authorities in the United States. Patients are currently being enrolled in this study.
Baum
Bruce J
BJ
Molecular Physiology and Therapeutics Branch and Clinical Research Core, National Institute of Dental and Craniofacial Research, NIH, Bethesda, MD 20892, USA. bbaum@dir.nidcr.nih.gov
Zheng
Changyu
C
Cotrim
Ana P
AP
McCullagh
Linda
L
Goldsmith
Corinne M
CM
Brahim
Jaime S
JS
Atkinson
Jane C
JC
Turner
R James
RJ
Liu
Shuying
S
Nikolov
Nikolay
N
Illei
Gabor G
GG
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D051398:Aquaporin 1 / Q000096:biosynthesis* / Q000235:genetics; D002460:Cell Line; D002986:Clinical Trials as Topic; D004195:Disease Models, Animal; D018014:Gene Transfer Techniques / Q000009:adverse effects; D015316:Genetic Therapy / Q000009:adverse effects / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans; D011832:Radiation Injuries / Q000209:etiology / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D011878:Radiotherapy / Q000009:adverse effects; D012107:Research Design; D012469:Salivary Glands / Q000378:metabolism* / Q000528:radiation effects; D014987:Xerostomia / Q000209:etiology / Q000235:genetics / Q000378:metabolism / Q000628:therapy*
C496020:AQP1 protein, human; D051398:Aquaporin 1