Mucopolysaccharidoses disorders
Mucopolysaccharidoses (MPS) disorders are inherited metabolic diseases that occur at a frequency of about 1 in 7,700 live births. The disease results from a deficiency in lysosomal enzymes involved in the degradation of glycosaminoglycans (GAG). In general, MPS diseases are associated with progressive systemic tissue pathology and, in severe forms, with neurological dysfunction and mental retardation. MPS type I, which is caused by the deficiency of alpha-L-iduronidase, is the most common MPS disease with variable clinical phenotypes ranging from Hurler syndrome to Scheie syndrome. The progression of disease includes visceral, cardiovascular, pulmonary, hematological and skeletal disease manifestations, as well as CNS abnormalities in severe patients. Many of these patients would die before age 10 without treatment. MPS I is thus a model disease entity for therapeutic studies of many inherited and acquired diseases. Animal models (e.g., mouse MPS I) are available to provide in vivo evaluation of potential therapeutic effects. Allogeneic bone marrow transplantation (BMT) has demonstrated variable degree of clinical response in MPS I patients, but is limited by the risk of significant mortality, high rate of engraftment failure and complications related to graft-versus-host disease. Enzyme replacement therapy, which was pioneered by Dr. Greg Grabowski at CCHMC, has led to clinical improvement in some patients with non-neuronopathic forms of Gaucher disease. However, it has proven far less efficient in the treatment of neurological complications of lysosomal storage diseases due to the existence of brain-blood barrier (BBB). We aim to study both in vivo and ex vivo stem cell gene transfer, with the hope of potentially providing a more efficient life-long treatment of the CNS and the hematopoietic system for MPS I patients.
Related Publications
Where possible, article titles are linked to an abstract of the article. Selected citations may also be linked to PDFs of the article available on a Journal's site. Depending on the Journal's publishing policy, you may need a subscription to download the PDF.
Schiffmann, R. and R.O. Brady, New prospects for the treatment of lysosomal storage diseases. Drugs, 2002. 62(5): p. 733-42.
Sly, W.S., Enzyme replacement therapy: from concept to clinical practice. Acta Paediatr Suppl, 2002. 91(439): p. 71-8.
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For additional information, please contact Dr. Dao Pan Division of Experimental Hematology, at 513-636-6315. Dr. Pan's office can be found in room 6529 of Location R (Research Foundation Building).
