This Small Business Innovation Research (SBIR) Phase II project aims to further develop ATX-Red, an in vivo imaging agent that becomes fluorescent in the presence of the enzyme autotaxin. Autotaxin and its product LPA are involved in numerous biological functions that generally involve cell movement, and their dysregulation is associated with many diseases including cancer, fibroses, cardiovascular disease, and others. In Phase I ATX-Red generated highly informative images in living organisms, essentially ?lighting up? tumors. In Phase II ATX-Red metabolic stability will be improved and increased performance will be demonstrated. Then ATX-Red will be used to monitor progression and treatment of breast cancer and pulmonary fibrosis in mice.
The broader impacts of this research are improvements to basic research, drug discovery, clinical diagnosis and disease treatment, with the ultimate result being an improvement to human health. ATXRed will be an indispensible tool to the many basic research fields associated with autotaxin and LPA, where questions regarding autotaxin in vivo were essentially unanswerable prior to the development of this tool. In addition to its usage in the research arena, ATX-Red will aid development of therapeutics. Currently significant efforts are underway to develop drugs targeting autotaxin pathways. ATX-Red will likely be employed in the extensive in vivo experimentation needed to develop these compounds. Human patients also stands to benefit from this research, since ATX-Red could act as a companion diagnostic for pharmaceuticals targeting diseases associated with autotaxin dysregulation. Further clinical applications might include diagnosing disease and even directing surgical resection of tumors.
Echelon Biosciences has developed a powerful tool for imaging tumors in live animals. ATX-Red AR-2 is an exciting advancement for pre-clinical drug discovery and development, allowing researchers the ability to monitor diseases and drug candidates using a non-invasive, mechanism-specific diagnostic. Visualizing the activity of an enzyme, autotaxin (ATX), that is elevated in a variety of diseases, including many cancers, promotes the development of treatments for these diseases by allowing researchers to witness the effectiveness of a drug candidate in a live animal non-invasively -- no surgical procedure is required. ATX-Red AR-2 enables researchers to validating that a drug candidate works against its intended target in a living animal. This overcomes a significant hurdle in the therapeutic development process that is often a bottleneck for pre-clinical drug development. Researchers at Echelon Biosciences engineered ATX-Red AR-2 to include proprietary dyes licensed from LI-COR Biosciences that emit light when viewed in the near-infrared spectrum, which is ideal for imaging in animals. When administered intravenously, ATX-Red AR-2 specifically targets ATX, which activates the probe causing it to emit light. In the absence of ATX there is no emission of light. Or, if the activity of ATX is blocked, for example by a drug candidate, there is also no light emission. Researchers can measure the effectiveness of their potential drug candidate by viewing the amount of light the probe emits – a decrease in signal reflects successful disease suppression. ATX is essential for cell growth – in both normal physiology and in several diseases – with elevated levels found in many cancers, including those of the breast, pancreas, kidney and brain. ATX is also involved in diseases such as arthritis, multiple sclerosis, Alzheimer’s disease, neuropathic pain and obesity. As a result, there is considerable effort to develop drugs that are active against ATX, as this enzyme has a fundamental role in multiple diseases. If future studies show that ATX-Red AR-2 is effective and safe, this tool could potentially be used to improve human health in several ways. Physicians could locate tumors more easily and determine if therapies are effective – if surgical resection is needed, ATX-Red AR-2’s ability to illuminate the cancerous tissue could make the surgeon’s job much easier. Additional research of ATX-Red AR-2 demonstrates applications in tumor and arthritis treatment, and other processes where ATX activity is elevated.
