Enzyme Replacement Therapy for Sanfilippo A Lysosomal Rare Disease

DESCRIPTION (provided by applicant): Current practice in the USA for inoperable esophageal cancer is a palliative treatment using metal stent for end-stage cancer patients. Outside the USA (especially in Far East countries including China and Korea), therehave been reported clinical benefits of attaching sealed sources such as prostate seeds to the outside of an esophageal stent. Although simple and preliminary, such radioisotope sources had doubled the mean survival period with high statistical confidence. The investigators have analyzed the current state-of-the-art and have formed a critical cluster of interdisciplinary experts for the development of advanced radioactive esophageal stents that will maximize dose to the tumors and significantly shorten thedose delivery time to more quickly achieve maximized clinical benefits. The Phase I research focuses on the therapeutic energy of radioisotopes and the integration of radioisotope sources with popular stents. The ultimate goal is to improve treatment efficacy by matching radiation dose distribution to tumor distribution. The specific aims include (1) identifying the best radioisotope sources for integration with the best esophageal stents; (2) preserving the device classification as 510K for faster FDA approval. The Phase II research will begin with in vivo biocompatibility assessment and end with preliminary clinical assessment using the proposed advanced radioactive esophageal stents. PUBLIC HEALTH RELEVANCE PUBLIC HEALTH RELEVANCE: The successful introduction of radioactive esophageal stent has the potential to dramatically improve the efficacy of esophageal cancer treatment, especially for earlier stage inoperable esophageal cancers. The use of proper radiation sources is expected to improve the safety and efficacy of radioactive esophageal stent. This project is to establish the feasibility of new radioactive esophageal stent with personalized dosimetry, to fill the void in the USA for radioactive esophageal stents, and to increase the USA's competitiveness in esophageal cancer treatment. With early detection and accurate dosimetry, it is possible to elevate the palliative esophageal treatment to a possible cure for inoperable esophageal cancers.