Enzyme replacement therapy for lysosomal storage disorder patients

There are 38 known genetic diseases that lead to a breakdown in lysosome function and the pathological storage of substrates in lysosomes. These disorders are known as lysosomal storage disorders (LSD). The importance of LSD to health care becomes obvious when the group incidence rate for LSD (at least 1:5,000) is compared with well-known and intensively studied genetic disorders such as cystic fibrosis (1:2,500) and PKU (1:15,000). All LSD result from a deficiency of enzymes that are involved in the degradation of macromolecules (such as mucopolysaccharides, glycolipids, glycoproteins) or the transport of the products of degradation (such as amino acid, monosaccbarides and inorganic sulphate) out of the lysosome to be recycled. The deficiency of a particular enzyme activity results in lysosomal storage of the substrate for that enzyme. A number of therapies are currently in use or are under evaluation for various LSD types. Bone marrow transplantation has been tried for a number of LSD with some, but limited success. Gene therapy trials for some LSD patients are planned. However, the most effective therapy so far has been enzyme replacement (ERT) for Gaucher disease (a glycolipid LSD). We have been developing ERT for a group of LSD known as the mucopolysaccharidoses (MPS). There are 10 different MPS and we have prepared recombinant enzymes for MPS types I, II, IIIA, IIIB, IIID, IVA and VI. Preliminary results with MPS-VI cats treated with human recombinant N-acetylgalactosamine-4-sulphatase have been most encouraging. We anticipate clinical trials for some of these MPS conditions within a year or two.