Principes des approches thérapeutiques pour les mucopolysaccharidoses

Abstract

Mucopolysaccharidoses (MPS) are caused by a deficiency of enzymes involved in the catabolism of glycosaminoglycans (GAGs) and are multisystemic diseases, often including the central nervous system. Despite their rare prevalence, specific treatments for MPS are available. One of them is enzyme replacement therapy, which provides the missing enzyme in the form of a recombinant protein administered intravenously. The effectiveness of this treatment relies on the enzymes being taken up by the different tissues via mannose-6-phosphate receptors. Treatment is currently available for MPS I, II and VI, and may be available for other forms of the disease in the near future. An alternative in MPS I is hematopoietic stem cell transplantation, the indications for which must be very clearly defined, particularly given the inherent risks of the procedure. Other new treatment strategies are currently being investigated, including substrate reduction therapy which uses GAG biosynthesis inhibitors (genistein,...), which reduces the accumulation of pathological compounds and their repercussions on tissues. Other molecular therapies using molecular chaperones or read-through molecules for stop codon mutations are also being studied. Finally, gene therapy, by introducing a normal gene sequence through a viral vector, either directly or using genetically modified cells, is a potential future method (the first clinical trials are undergoing).