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Late responses to adenoviral-mediated transfer of the aquaporin-1 gene for radiation-induced salivary hypofunction
- Source :
- Gene therapy
- Publication Year :
- 2016
- Publisher :
- Springer Science and Business Media LLC, 2016.
-
Abstract
- We evaluated late effects of AdhAQP1 administration in five subjects in a clinical trial for radiation-induced salivary hypofunction (http://www.clinicaltrials.gov/ct/show/NCT00372320?order=). All were identified as initially responding to human aquaporin-1 (hAQP1) gene transfer (Baum et al, 2012). They were followed for 3-4 years after AdhAQP1 delivery to one parotid gland. At intervals we examined salivary flow, xerostomic symptoms, saliva composition, vector presence and efficacy in the targeted gland, clinical laboratory data, and adverse events. All displayed marked increases (71-500% above baseline) in parotid flow 3-4.7 years after treatment, with improved symptoms for ~ 2-3 years. There were some changes in [Na+] and [Cl−] consistent with elevated salivary flow, but no uniform changes in secretion of key parotid proteins. There were no clinically significant adverse events, nor consistent negative changes in laboratory parameters. One subject underwent a core needle biopsy of the targeted parotid gland 3.1 years post treatment and displayed evidence of hAQP1 protein in acinar, but not duct, cell membranes. All subjects responding to hAQP1 gene transfer initially had benefits for much longer times. First generation adenoviral vectors typically yield transit effects, but these data show beneficial effects can continue years after parotid gland delivery.
- Subjects :
- 0301 basic medicine
Genetic enhancement
Genetic Vectors
Physiology
aquaporin-1
Biology
Gene delivery
Xerostomia
Article
clinical
Salivary Glands
Adenoviridae
03 medical and health sciences
0302 clinical medicine
Chlorides
stomatognathic system
Biopsy
Genetics
medicine
Humans
Adenoviral vector
Secretion
Adverse effect
Molecular Biology
Aquaporin 1
Radiotherapy
medicine.diagnostic_test
Sodium
Genetic Therapy
Middle Aged
Molecular biology
Parotid gland
Clinical trial
030104 developmental biology
medicine.anatomical_structure
parotid
radiation damage
030220 oncology & carcinogenesis
Molecular Medicine
Subjects
Details
- ISSN :
- 14765462 and 09697128
- Volume :
- 24
- Database :
- OpenAIRE
- Journal :
- Gene Therapy
- Accession number :
- edsair.doi.dedup.....28ac1065b4992f25099c98ff9b41acad