title: Aquaporin-1 gene transfer to correct radiation-induced salivary hypofunction.
abstract: 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.
authors.affiliation: 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
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: Linda
authors.initials: L
authors.lastname: McCullagh
authors.forename: Corinne M
authors.initials: CM
authors.lastname: Goldsmith
authors.forename: Jaime S
authors.initials: JS
authors.lastname: Brahim
authors.forename: Jane C
authors.initials: JC
authors.lastname: Atkinson
authors.forename: R James
authors.initials: RJ
authors.lastname: Turner
authors.forename: Shuying
authors.initials: S
authors.lastname: Liu
authors.forename: Nikolay
authors.initials: N
authors.lastname: Nikolov
authors.forename: Gabor G
authors.initials: GG
authors.lastname: Illei
mesh_terms: 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*
chemical_list: C496020:AQP1 protein, human; D051398:Aquaporin 1