%0 Journal Article
%T Gene therapy for inborn errors of liver metabolism: progress towards clinical applications
%A Nicola Brunetti-Pierri
%J Italian Journal of Pediatrics
%D 2008
%I BioMed Central
%R 10.1186/1824-7288-34-2
%X Significant advances in the diagnosis and treatment of inborn errors of metabolism have occurred in recent years. Expanded newborn screening using tandem mass spectrometry has led to the ability to identify and treat neonates who have metabolic conditions before symptoms appear [1]. Developments in nutritional support and pharmacological treatments with vitamin cofactors, end-product replacement, and drugs inducing specific enzymes or alternative pathways have also led to better outcomes. Cell therapy, primarily orthotopic liver transplantation (OLT), has significantly changed the prognosis of some of these diseases. Patients undergoing solid organ transplantation have benefited from innovative surgical techniques and novel, less toxic nonsteroidal immunosuppressive regimens. However, pharmacological treatments are often insufficient in the face of the activation of catabolic states, many patients succumb while waiting for a donor organ (approximately 15%), and short-term peri-transplant morbidity and long-term morbidity associated with lifelong immunosuppression continue to be significant issues [2-5]. Therefore, a risk/benefit assessment could make gene therapy an acceptable option for several inborn errors of metabolism.Progress in the direction of clinical application of gene replacement therapy has been scarce so far despite extensive investigations for over 20 years. A general skepticism toward gene therapy was raised by the death of one patient in the ornithine transcarbamylase deficiency (OTCD) clinical trial [6] and by the recent report of leukemia occurred in few patients with severe combined immunodeficiencies (SCID) treated with retroviral ex vivo gene therapy [7]. However, with regard to the SCID trial, it is important to emphasize that despite the adverse events, it clearly demonstrated the benefits of gene therapy as treated patients can now cope with environmental microorganisms and live a normal life in the absence of any specific therapy [8].Severa
%U http://www.ijponline.net/content/34/1/2