It is estimated that the annual incidence of spinal cord injury (SCI), not including those who die at the scene of the accident, is approximately 11,000 cases each year. The number of living patients in the United States as of December 2003 who have SCI, has been estimated as being approximately 243,000 persons. After initial injury, about half of those affected will remain completely paralyzed below the level of their spinal lesion. In the other half, the lesion is """"""""incomplete"""""""" and some movement and/or sensation is preserved. Hepatocyte growth factor (HGF), also known as Scatter factor (SF), was originally identified and cloned as a potent mitogen for hepatocytes, HGF/SF is produced by mesenchyme and acts upon target cells via its receptor, Met. HGF/SF, has documented scattering, proliferative, and protective effects on neurons in the brain, spinal cord, and peripheral nerves and has significant potential as a novel therapeutic for the treatment of brain and spinal cord injures. Administration of ah HGF/SF-like compound holds promise as a new approach to the clinical management of SCI. However, treatment modalities that employ gene- or protein- based formulations are characteristically expensive and difficult to administer. Therefore, therapeutic approaches that employ small molecule mimetics of natural growth and protective factors may be powerful alternatives to such therapies. The primary focus of research at Angion Biomedica is the development of small molecules that regulate SF/HGF/Met signaling to therapeutic advantage. Using phage display technology we have identified novel peptide ligands functionally identical to HGF/SF for Met receptor interaction. Our lead small molecule HGF/SF mimetic has been termed Refanalin (Rf). Preliminary data indicates that Rf recapitulates the biologic activity of HGF/SF in vitro by activating the HGF/SF receptor, Met resulting in impressive pro-proliferative, scattering and anti-apoptotic effects in Schwann cells. In addition Rf appears to stimulate axonal growth. Furthermore, in a preliminary in vivo study using the spinal cord ischemic injury rabbit model, we show an 80 percent recovery benefit for Rf treatment. Administration of this small molecule mimetic of HGF/SF, represents a highly innovative approach to the treatment of spinal cord injures, with significant clinical potential. ? ? ? ? ?
