Many experimental therapies will rely on the local parenchymal delivery of macromolecules or nucleic acids for their success. However, the volume of distribution of many of these potential therapeutic agents is restricted by their interactions with the extracellular matrix and cellular receptors. Heparin-sulfate proteoglycans are cell surface components which bind to many different types of molecules such as growth factors, cytokines and chemokines and viruses such as cytomegalovirus, herpes simplex virus and HIV.
These inventions provide a method of dramatically increasing the volume of distribution and effectiveness of certain therapeutic agents after local delivery by the use of facilitating agents as described in Neuroreport. 2001 Jul 3;12(9):1961-4 entitled "Convection-enhanced delivery of AAV-2 combined with heparin increases TK gene transfer in the rat brain" and in Exp Neurol. 2001 Mar;168(1):155-61 entitled "Heparin coinfusion during convection-enhanced delivery (CED) increases the distribution of the glial-derived neurotrophic factor (GDNF) ligand family in rat striatum and enhances the pharmacological activity of neurturin." These methods are especially useful when used in conjunction with technology described and claimed in U.S. Patent 5,720,720 entitled "Convection-enhanced drug delivery." Licenses for methods to enhance the distribution of all claimed therapeutics except adeno-associated viral vectors are available.