Aldurazyme®, administered once weekly, has been approved in the European Union for the long-term enzyme replacement therapy (ERT) in patients with a confirmed diagnosis of MPS I, to treat the nonneurological manifestations of the disease. Aldurazyme was developed by BioMarin and Genzyme under a joint venture agreement that assigns commercial manufacturing responsibilities to BioMarin, and worldwide sales and marketing responsibilities to Genzyme. Aldurazyme is a weekly infusion lasting 3 – 4 hoursthat is usuallyadministered at home. Additional information can be obtained at www.aldurazyme.com
Vimizim® is a long term ERT for patients with a confirmed diagnosis of MPS IVA, as approved for use in the European Union since April 2013. Vimizim was developed and is produced by BioMarin Pharmaceuticals Inc. and is given as a weekly infusion over a period of 3 – 4 hours. Additional information can be obtained at www.vimizim.com
Naglazyme®, is the ERT for individuals with a confirmed diagnosis of MPS VI and has been approved for use in the European Union. It was developed and is produced by BioMarin Pharmaceuticals, Inc. Naglazyme is a weekly infusion lasting 3 – 4 hours that is administered at home. Additional information can be obtained at www.bmrn.com
To date, HSCT represents one of the few therapies with proven, long-term benefit for some, but not all, MPS diseases. The MPS diseases benefiting most significantly from HSCT include MPS I (Hurler), MPS VI (Maroteaux-Lamy), and MPS VII (Sly). Unfortunately, benefit from HSCT for the nervous system and/or the skeletal system has not been shown for MPS II (Hunter), MPS III (Sanfilippo) and MPS IV (Morquio).
Successful HSCT (then known as a bone marrow transplant) has been performed for children with Hurler since 1980. The immediate benefits include correction of the enzyme deficiency and clearance of glycosaminoglycans (GAGs). Long-term benefits include the possibility of long-term survival by protecting the heart, lungs, and brain from the effects of progression of the MPS disease. Other organs and tissues can also show benefits from the HSCT; these include the eyes and ears, liver, spleen, joints, airway, etc. However, it should be noted that many children and adults are still requiring a range of orthopeadic surgeries despite a successful transplant. While the term “cure” should not be used, HSCT has the longest track record of any effective therapy for Hurler disease, including in some cases the ability to preserve cognitive function and development in the normal range.
The principal clinical features of children with MPS VI are bone abnormalities, severe short stature, corneal clouding, respiratory problems, liver and spleen enlargement, and heart valve abnormalities. Intelligence is usually preserved in most individuals. For over twenty years, HSCT has been used successfully in some countries to treat MPS VI with resolution of liver and spleen enlargement, airway obstruction and sleep apnea, and improved joint mobility. It is reported that there has been prevention of further cardiac and respiratory deterioration. Visual acuity has improved in some individuals although corneal haze does not necessarily resolve. As in other MPS diseases, HSCT has not been able to treat effectively the skeletal abnormalities or improve growth. Consequently, successfully transplanted children and adults still require orthopeadic surgical interventions on the knees, hips and spine.
Use of HSCT for MPS VII is limited by the rarity of the disorder and tendency toward stillbirths, although there are also children and adults with attenuated forms of this disease. In certain circumstances, MPS VII can be effectively treated by HSCT provided that the developmental and clinical status of the individual is good at the time of HSCT.