14154 Background: There is a major unmet need for new non-toxic orexigenic and cytoprotective agents that can ameliorate intractable symptoms in cancer such as anorexia, poor wound healing/ulcerations and poor QoL. Underlying causes of these clinical problems include excessive inflammatory/cytokine responses to either treatment related or tumor related processes, or to both at once. AVR118, a novel remarkably non-toxic peptide/nucleic acid formulation has been shown in many anecdotal reports and in small clinical trials, to stimulate appetite, improve fatigue, and assist in more rapidly reversing toxic side effects of chemotherapy, radiation and interferon therapy. It has now been re-characterized to better explain these multiple effects. It binds to adenosine receptors in vitro and increases cAMP release in HEK293 cell lines expressing A2 receptors, mechanistically involving targeted receptor binding, most likely in the gut and in the functional pathway of orexin A. Methodologies: HPLC, co-chromatography with standards, UV and mass spectrometry. Receptor binding/functional assays in vitro, animal models for anti-inflammatory and wound healing studies. Results: AVR 118 consists of a mix of 14 nucleoside derivatives, including available adenosine at a concentration of 2.1mM in stable solution. Also present is a complex aggregate of peptides showing high proline and tyrosine content. AVR 118 binds to adenosine receptors in vitro and increases cAMP release in HEK293 cell lines containing A2 receptors and enhances smooth muscle relaxation mediated by A2 and others such as NK2 and NTS1 in vitro. AVR 118 shows 20% enhancement of epithelialization when compared to saline controls in a controlled porcine wound healing model. Conclusions: AVR 118 may prove to play a major role in palliation of anorexia symptoms associated with serious debilitating diseases such as cancer or AIDS and as adjunctive therapy for these patients. [Table: see text] No significant financial relationships to disclose.
Peptide nucleic acid (PNA) binding and its effect on in vitro transcription in friedreich's ataxia triplet repeats
