Magnetic Flow Sorter for Pancreatic Islet Isolation

DESCRIPTION (provided by applicant): Bone metastasis is common in patients with advanced breast, prostate, and lung cancers as these tumors have a remarkable ability to metastasize to bone. Two-thirds of patients with metastatic bone cancer experience severe pain which is usually described as dull in character, constant in presentation, and gradually increasing in intensity with time. Bone cancer pain is one of the most difficult of all persistent pains to control because the metastases are generally not limited to a single site and bone cancer pain is associated with unique pathophysiology. Nonsteroidal anti-inflammatory drugs (NSAIDs) and opioids are the most commonly used an- algesics, but are limited by significant adverse side effects, such as gastric bleeding and neuropsychiatric symptoms. APT102 is a proprietary, optimized human apyrase of the CD39 family. APT102 selectively scav- enges excess pro-inflammatory and algogenic ATP and pro-metastatic ADP to AMP, thereby attenuating vas- cular inflammation,preventing metastasis, and reducing pain. Ubiquitous CD73 further metabolizes AMP to adenosine, which has been shown to reduce neuropathic pain in humans. Hence, the analgesic effect of APT102 results both from the elimination of ATP and from the production of adenosine. In the proposed studies, we will evaluate the dose-response of APT102 in a model of osteolytic bone cancer pain. This model is driven by in- tra-tibial injections of syngeneic MRMT-1 rat mammary gland carcinoma cells and closely mirrors the human condition. We also will determine the potential side effects of APT102 in the rotarod and Functional Observa- tional Battery (FOB) assays in healthy rats. The long-term goal is to develop APT102 as a safe and effective analgesic therapy. Weekly orbi-weekly dosing will provide sustained pain relief for bone cancer pain patients without significant side effects or addiction. PUBLIC HEALTH RELEVANCE PUBLIC HEALTH RELEVANCE: The analgesic effect of human apyrase results both from the elimination of ATP and from the production of adenosine. In the proposed studies, we will evaluate the dose-response of APT102, an optimized human apyrase, in a model of osteolytic bone cancer pain. The long-term goal is to develop APT102 as a safe and effectiveanalgesic therapy for bone cancer pain patients without significant side effects or addiction.