![]() In comparison, CERE-120 post-IR treatment groups only showed similar saliva flow to the non-IR group at 300 days, not at 90 and 120 days post-IR ( Figures 1C and 1D). At 120 days, there were differences in the 3 doses with CERE-120 at 10 8 and 10 10 vp/g being similar to non-IR. All CERE-120 treatments pre-IR (10 6, 10 8, 10 10 vp/g) resulted in improved saliva flow compared to the IR-GFP group and were similar to the non-IR group at 90 and 300 days. Saliva was collected 90 days post-IR, and the IR control group produced ∼65% less saliva compared to the non-IR group (baseline), irrespective of whether the AAV2-GFP was delivered pre- or post-IR ( Figures 1C–1E). ![]() Which was measured by pilocarpine stimulation of whole saliva production. CERE-120 gene therapy is a potential treatment for head and neck cancer patients to influence communication among neuronal, immune, and epithelial cells to prevent IR-induced salivary hypofunction and restore immune homeostasis. CERE-120 prevented IR-induced hypofunction and restored immune homeostasis, and there was a coordinated contralateral gland response to either damage or treatment. Analysis of gene expression, morphology, and immunostaining showed reduced IR-related immune responses and improved secretory mechanisms. We then used a minipig model with CERE-120 treatment pre-IR and also compared outcomes of the contralateral non-IR gland. RNA sequencing (RNA-seq) analysis showed reduced gene expression associated with fibrosis and the innate and humoral immune responses. Treatment with CERE-120 pre-IR, not post-IR, prevented hypofunction. We used an adeno-associated virus serotype 2 (AAV2) vector expressing the human neurotrophic factor neurturin (CERE-120) to treat murine submandibular glands either pre- or post-irradiation (IR). Preventing hypofunction is an unmet therapeutic need. Salivary gland hypofunction causes significant morbidity and loss of quality of life for head and neck cancer patients treated with radiotherapy. Gene Editing: Technology & Applications.
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