14800-DvRappard

36 Chapter 2 which has proven to be able to stop the disease. One of the main problems regarding HSCT is the slow replacement of resident tissue compared to rapid progression of the disease. It can take 12 to 24 months until the disease stabilizes, which makes HSCT ineffective for patients with overt neurological symptoms or for those with the aggressive infantile onset type. 1 In these patients, who are already symptomatic at the time of transplantation, neurologic involvement continues to deteriorate. 21 Even in asymptomatic patients with the infantile onset type, neurological deterioration and progression of white matter abnormalities on MRI were reported, 22 suggesting that disease progression is too fast for HSCT to influence. When HSCT was performed in patients suffering from the juvenile and adult form of MLD, both cerebral demyelination as well as disease progression have been reported to be delayed or stopped. 23-25 Even improvements in motor and behavioral functions have been reported, together with a decrease of the white matter abnormalities seen on MRI. 26-28 However, also cases, in which the disease takes the natural course or even worsens, have been reported. Smith et al 29 report a case of a symptomatic patient with adult onset MLD in which HSCT does not halt disease progression and results in relentless cognitive decline. Hosson et al 30 describe 5 symptomatic patients with adult onset MLD who were treated with HSCT. Stabilization of the disease occurred only in one of the five patients who later also experienced disease progression. Levels of donor chimerism (and achieved enzyme level) are important, as mixed chimerism will dilute the post- HSCT enzyme level. In other lysosomal storage diseases, such as mucopolysaccaridosis(MPS) 1, the enzyme level achieved after HSCT is associated with long-term outcome, including development. 31,32 Mesenchymal stem cells (MSC) are non-hematopoietic multipotent stem cell-like cells that are capable of differentiating into both mesenchymal and non-mesenchymal lineages. They have been found to be able to differentiate into neurons and astrocytes. Because of these capabilities, concomitant infusion of MSC with HSCT has been performed for a symptomatic patient with adult onset MLD by Meuleman et al. 23 She had a complete stabilization of her disease during the 40-month follow up period. Apart from the uncertain long-term effects, HSCT is furthermore complicated by substantial risks of the procedure and post-transplant complications such as graft versus host disease (GvHD) and infections. Mortality is estimated to be 10 to 15%, improving over time. Another limitation of HSCT is the fact that the involvement of the peripheral nervous system does not seems to be influenced, causing severe motor impairment in a substantial part of transplanted patients. 7