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Allegheny Health Network Researchers Move Toward First Clinical Trial of Innovative Gene Therapy Technique to Treat Xerostomia, a Common Cancer Treatment Side Effect

Friday, December 7, 2018

NIH Support Allows Researchers to Petition FDA for Investigational New Drug Status for Technology That Uses Ultrasound to Transmit Gene Therapy to Patients’ Cells

PITTSBURGH, Pa.  – The Michigan-Pittsburgh-Wyss Regenerative Medicine Resource Center has awarded researchers from Allegheny Health Network (AHN) and the University of Michigan $92,000 to advance research of a new gene transfer technology that could help patients suffering from xerostomia (dry mouth), a devastating side effect of radiation treatment for head and neck cancers. The resource center is supported by the National Institutes of Health (NIH)/National Institute of Dental and Craniofacial Research.

Researchers Michael J. Passineau, Ph.D., of AHN and Isabelle Lombaert, Ph.D., of the University of Michigan will complete preclinical studies of their Interdisciplinary Translational Project (ITP) needed to petition the U.S. Food and Drug Administration to authorize an IND (Investigational New Drug) application. This would lead to a Phase I clinical trial of a technology that uses ultrasound to deliver a gene drug known as Aquaporin-1 (AQP1) directly to the patient’s salivary gland, potentially resulting in restoration of salivary flow.

Hundreds of thousands of cancer patients suffer from radiation-induced xerostomia, a treatment side effect that causes severe tooth decay, pain, loss of taste, inability to eat properly and increased oral infections, all of which greatly diminish the quality of life in survivors of head and neck cancers.  Once xerostomia onset begins, it is a permanent condition. 

Medications offer little relief, and researchers have turned to gene therapy – treating a disease by genetically modifying a patient’s cells - in search of an effective treatment. But delivering gene therapy to the salivary glands without complications has proven difficult.

A recent Phase I clinical trial used an adenoviral vector to deliver AQP1 gene therapy directly to the salivary gland via an oral cannula, and successfully increased saliva production. However, the technology is not advancing due to concerns about the inflammatory response created by the virus, making it difficult to provide repeated treatments.

“Our solution, ultrasound-assisted gene transfer (UAGT), delivers gene drugs to the salivary glands through sonoporation – using sound to permeate a cell’s membrane - rather than viral infection,” said Dr. Passineau, Director of Gene Therapy for AHN.  “This approach avoids activating the patient’s immune response, and makes it possible to provide repeat treatments, whenever the patient begins to feel dryness returning. We believe this solution will allow patients suffering from radiation-induced xerostomia to benefit from AQP1 gene therapy throughout their lives.”

“While head and neck cancers linked to tobacco use are declining, the number of cancers linked to HPV, human papilloma virus, is increasing,” said Mark Trombetta Director of Clinical Program Development, AHN Cancer Institute, and a Co-Investigator on this study.  “Thus, we expect the incidence of xerostomia to remain stable in the coming years. We believe that our technology may provide long-lasting relief of radiation-induced xerostomia, with adjustable dosing and potential for booster doses over time. No other existing treatment offers long-lasting relief for this life-altering condition.”

“Thanks to new, advanced treatments, cancer is now often treated as a chronic disease that patients live with for many years,” said David Parda, MD, Chair, Allegheny Health Network Cancer Institute. “In keeping with AHN’s philosophy of holistic, patient-centered care, we want them to retain a good quality of life during those years. So it is important for us to effectively treat the side effects of their treatments, particularly life-altering side effects such as xerostomia.”

“We are excited to see Dr. Passineau and his team making this contribution to gene therapy research and development, a novel approach to cancer therapy that holds much promise,” Dr. Parda said. “These researchers follow in the long tradition of AHN researchers and clinicians who have changed the way cancer is treated, from proving the value of lumpectomies to establishing tamoxifen and raloxifene as medications that help prevent breast cancer recurrence.”