Dr Cary O Harding
Inborn errors of metabolism (IEM) affect as many as 1:1500 people with age of onset varying from birth to adulthood. For many of these disroders, contemporary medical therapy is less than satisfactory. Gene therapy is a promising new approach to the treatment of IEM. The focus of our laboratory is the development of liver- or muscle-directed gene transfer for the treatment of IEM. Most of our efforts are concentrated upon gene transfer into the Pahenu2 mouse, a model of phenylketonuria which is a common human IEM. We are exploring a variety of viral (predominately adeno-associated virus (AAV)) and DNA-based gene transfer technologies to introduce the phenylalanine hydroxylase (PAH) cDNA into phenylketonuric mice. Additionally, we are investigating hepatocyte and bone marrow stem cell transplants as a possible therapy for PKU.
Understanding the pathophysiology of IEM is a critical requirement for the design and execution of any treatment protocol, including gene therapy. In anticipation of improved future therapies, we continue to investigate the abnormal physiology and biochemisty involved in a variety of human IEM. Currently, disorders of fatty acid oxidation are of central interest in our research program.