Laronidase for treating mucopolysaccharidosis type I

Mucopolysaccharidoses are a group of inherited metabolic diseases caused by the absence or deficiency of the lysosomal enzymes that are needed for breaking down glycosaminoglycans (GAGs). Over time, GAGs collect in cells, blood and connective tissues, and increased amounts are excreted in the urine. The result is permanent and includes progressive cell damage that affects the individual’s appearance, physical abilities, organ and system functioning and, in certain cases, mental development. Enzyme replacement therapies are currently in use or are being tested for at least three different subtypes (I, II and VI). The aim of the present study was to evaluate the effectiveness and safety of laronidase for treating mucopolysaccharidosis type I. A systematic review of the literature was conducted. A computerized electronic search was then conducted using the CENTRAL, Pubmed, EMBASE, and LILACS databases, to identify any randomized controlled trials. The last date of the search was June 2006. There was no possibility of combining the results, because only one study was included. In the pivotal placebo-controlled trial conducted over a 26-week period, there was a reduction in the urinary excretion of GAGs among treated patients. Regarding adverse events, there were no laronidase-related serious adverse events or deaths. Laronidase seems to be a promising agent for treating mucopolysaccharidosis type I, as shown by the reduction in the urinary excretion of GAGs and the associated improvements in vital capacity and in the performance of defined physical tasks.

Extended interval between enzyme therapy infusions for adult patients with Gaucher's disease type 1.

BACKGROUND: Enzyme replacement therapy (ERT) for Gaucher's disease with alglucerase or imiglucerase is efficacious, well-tolerated and safe. However, cost considerations, visits to medical facilities, potentially duration of theray for life, are issues of major concern to a proportion of treated patients and has, in some cases, led to the withdrawal of therapy. AIMS: To elucidate whether an extension of the interval between enzyme infusions to once every three weeks is as effective in maintaining the clinical responses achieved with the bi-monthly regimen. MATERIALS AND METHODS: Four patients with an optimal response to ERT (at 30 units/kg every two weeks for an average of 27 months), were subjected to enzyme dose/frequency changes that essentially constituted a reduction in cumulative dose over the treatment period. Patients were assessed every 6 months for alterations in haematological parameters, plasma chitotriosidase levels, liver and spleen size, and bone symptoms. RESULTS: All patients had to resume the previous infusion schedule of once every two weeks; one because of new bone marrow infiltrates, two because of visceral enlargement, and the fourth due to progressive anaemia. CONCLUSIONS: This limited experience suggests that a reduction in enzyme dose associated with an extended interval between infusions may lead to variable disease control, and underscores the need for individualization of enzyme therapy.