 | Enzyme replacement therapy with Aldurazyme® (laronidase) |
| Symptomatic management |
| Bone marrow transplant |
Aldurazyme enzyme replacement therapy
Management of MPS I may now include Aldurazyme, a targeted enzyme replacement therapy that may help doctors and other health care professionals address the actual disease process itself. Aldurazyme is a polymorphic variant of the human enzyme deficient in MPS I, alpha-L-iduronidase. It is produced by recombinant DNA technology and is indicated for patients with Hurler and Hurler-Scheie forms of MPS I and for patients with the Scheie form who have moderate to severe symptoms. The risks and benefits of treating mildly affected patients with the Scheie form have not been established. With Aldurazyme, the many effects of MPS I may be eased and possibly reversed. Progressive accumulation of GAG may be stopped, which directly addresses the underlying cause of the disease.
Aldurazyme has not been evaluated for effects on the central nervous system manifestations of the disorder. [2]
Symptomatic management
Symptomatic management for MPS I includes using supportive care and the treatment of complications - with attention to the respiratory and cardiovascular complications, skeletal manifestations, arthropathy, loss of hearing and vision, gastrointestinal symptoms, and communicating hydrocephalus. Although these treatments are valid strategies in managing MPS I and typically improve the quality of life for patients and their families, they do not address the underlying cause of MPS I -- the alpha-L-iduronidase deficiency leading to progressive cellular accumulation of GAG throughout the patient’s body.
Examples of symptomatic management techniques include: [1]
| Oxygen for respiratory insufficiency |
| Continuous positive airway pressure (CPAP machines) |
| Tracheostomy for severe airway obstruction |
| Physical therapy for joint stiffness |
| Cardiac valve replacement therapy |
Bone marrow transplant
For the most severe patients, bone marrow or umbilical cord blood transplantation may be an option. [1] [3] Bone marrow transplantation (BMT) may improve some physical (especially facial) features and may stabilize CNS disease in some patients. With engraftment of donor marrow, the derived monocytes/macrophages enzyme activity is corrected.
However, BMT is restricted to severe MPS I patients because of the risks associated with this procedure. In general, the clinical outcome of BMT in patients with MPS I is varied and depends on the degree of clinical involvement and the age of the child at the time of transplantation. Failure to achieve stable engraftment and graft-vs.-host disease represent significant barriers to success for many patients. For patients with MPS I, BMT carries a high risk of morbidity and mortality. Due to the risks, BMT is primarily used to treat selected severe patients with MPS I.[1]
While BMT has modified disease progression and improved survival in some cases, it is not curative.[1] Ongoing issues in this area of treatment for MPS I include developing methods to accurately assess MPS I patients for significant disease-related risks prior to hematopoietic cell transplant, and addressing pneumonias, airway obstruction, poor cardiac contractility and hydrocephalus.
References:
1. Neufeld EF, Muenzer J. The mucopolysaccharidoses. In: Scriver CR, Beaudet AL, Sly WS, Valle D, Childs B, Kinzler KW, et al, editors. The Metabolic and Molecular Bases of Inherited Disease. Vol. III. 8th ed. New York: McGraw-Hill; 2001. p. 3421-52.
2. Aldurazyme® [package insert]. Novato, CA: BioMarin Pharmaceutical Inc.; 2003 (lines 4-8, 57-79, 80-7).
3. Whitley CB, Belani KG, Chang PN, Summers CG, Blazar BR, Tsai MY, Latchaw RR, et al. Long-term outcome of Hurler syndrome following bone marrow transplantation. Am J Med Genet 1993;46:209.
4. Aldurazyme® [package insert]. Novato, CA: BioMarin Pharmaceutical Inc.; 2003 (lines 80-7, 89, 148-58, 192-4, 297).
