Seattle, WA – January 23, 2024
Washington Research Foundation (WRF) has awarded a $250,000 phase 2 technology commercialization grant to support the development of a novel gene therapy for the treatment of severe asthma and eosinophilic esophagitis by investigators Sinduja Marx, Ph.D., and Jason Price, Ph.D., postdoctoral scholars at the Olson Lab in Seattle Children’s Research Institute. This project is in collaboration with Benaroya Research Institute’s Karen Cerosaletti, Ph.D., and Steven Ziegler, Ph.D. WRF previously provided Dr. Price with a phase 1 grant of $58,000 that supported the generation of antibody targets that will be used during the phase 2 antibody discovery campaign and the development of a new gene therapy platform.
Before being approved for human use, new medical treatments undergo rigorous testing in animal models. However, human therapeutic targets may be different or absent in animal models. These discrepancies can cause treatments that are ineffective or unsafe in animal models to be incorrectly deemed ineffective or unsafe in humans, hindering the progression of promising treatments to clinical trials. It is in this challenging landscape that a team led by Price and Marx pioneered a method for isolating antibodies that bind a desired protein target across different species. They are now using this method to discover cross-species reactive binders that will facilitate the development of a novel targeted gene therapy aimed at treating eosinophilic esophagitis and severe asthma.
Eosinophilic esophagitis (EoE) is a chronic disease in which abnormal immune responses to certain foods and allergens cause the cells lining the esophagus to excrete proteins called thymic stromal lymphopoietin (TSLP). These proteins promote inflammation, leading to pain and difficulty swallowing. Existing treatments for EoE include swallowed steroids that can have harmful side effects with prolonged use, and elimination diets that can be ineffective and challenging for patients to implement. Current antibody therapies target the TSLP signaling cascade but require expensive weekly injections. Price and Marx are developing a gene therapy that enables patients to produce their own antibodies targeting the TSLP receptor after a single treatment. These antibodies will block the TSLP signaling cascade to prevent inflammation.
This therapy has potential applications beyond treating EoE. Severe asthma is a result of inflammation in the airways triggered by TSLP, leading to pain and difficulty breathing. Furthermore, research indicates that TSLP plays a role in promoting tumor growth in various cancers, including colon cancer. Inhibiting the TSLP signaling pathway would not only be an effective approach for treating severe asthma but might also improve cancer therapies.
Having completed the phase 1 project, during which the team created structures they want their antibodies to target, they will now focus on developing antibodies capable of binding their target in multiple species. In future work, the researchers will develop a gene therapy in which patient immune cells are genetically engineered to excrete these effective antibodies.
“What we care about is improving patients’ lives,” Price said. “We are both pursuing a needed treatment and advancing the process of gene therapy development, paving the way for gene therapies for other diseases.”
“We are delighted to support this type of forward-looking innovation that is pushing boundaries in inventing medicines for the future,” said Meher Antia, Ph.D., WRF’s director of grant programs. “We hope that these studies will pave the way for future development of a one-time treatment for EoE and potentially other diseases.”