Non-Viral Aquaporin-1 Gene Therapy to Restore Salivary Flow

Radiotherapy is commonly used to treat head-and-neck cancers. Because of the anatomical proximity, salivary glands often receive secondary radiation damage, resulting in xerostomia. While intensity-modulated radiotherapy significantly reduces the incidence of radiation-induced xerostomia, a need still exists for patients suffering from xerostomia.

Ultrasound-assisted gene transfer is based on sonoporation generated by ultrasound, enabling gene transfer into cells. The delivery of a water channel to glands in a large animal model restored salivary flow post-radiation to pre-treatment levels, demonstrating efficacy of our non-viral gene transfer approach.

While a recent clinical trial using a viral-based AQP1 gene delivery demonstrated an increase in saliva production, this approach has not advanced beyond Phase I/II trial due to side-effects generated by the adenovirus vector. With our non-viral based approach, it is anticipated that enhanced safety is provided in patients with AQP1 gene therapy throughout their lifetime.

Since the start of the project in the ITP program in 2018, proof-of-concept for the anticipated product/ therapy has been established. The Resource Center Cores are supporting activities to enable the FDA IND submission. The ITP program has helped in deciphering the regulatory and commercialization path, and design/execution of studies needed for the FDA IND submission.

Securing non-diluted funding to support GLP Toxicology studies

• IND submission anticipated in 2025

• Obtaining funds to initiate first-in-human trial

• Wang et al. Ultrasound-assisted nonviral gene transfer of AQP1 to the irradiated minipig parotid gland restores fluid secretion. Gene Ther 2015