Iduronidase (EC 3.2.1.76, L-iduronidase, alpha-L-iduronidase, laronidase), sold as Aldurazyme, is an enzyme with the systematic name glycosaminoglycan alpha-L-iduronohydrolase. This enzyme catalyses the hydrolysis of unsulfated alpha-L-iduronosidic linkages in dermatan sulfate.It is a glycoprotein enzyme found in the lysosomes of cells. It is involved in the degeneration of glycosaminoglycans such as dermatan sulfate and heparan sulfate. The enzyme acts by hydrolyzing the terminal alpha-L-iduronic acid residues of these molecules, degrading them. The protein is reported as having a mass of approximately 83 kilodaltons. Pathology
A deficiency in the IDUA protein is associated with mucopolysaccharidoses (MPS). MPS, a type of lysosomal storage disease, is typed I through VII. Type I is known as Hurler syndrome and type I,S is known as Scheie syndrome, which has a milder prognosis compared to Hurlers. In this syndrome, glycosaminoglycans accumulate in the lysosomes and cause substantial disease in many different tissues of the body. IDUA mutations result in the MPS 1 phenotype, which is inherited in an autosomal recessive fashion. The defective alpha-L-iduronidase results in an accumulation of heparan and dermatan sulfate within phagocytes, endothelium, smooth muscle cells, neurons, and fibroblasts. Under electron microscopy these structures present as laminated structures called Zebra bodies. Prenatal diagnosis of this enzyme deficiency is possible. Aldurazyme
General
Aldurazyme is the name of the commercialized variant of the enzyme iduronidase, which hydrolyzes the alpha-L-iduronic acid residues of dermatan sulfate and heparin sulfate. Produced in Chinese hamster ovaries by recombinant DNA technology, Aldurazyme is the manufactured by BioMarin Pharmaceutical Inc. and distributed by Genzyme Corporation (a subsidiary of Sanofi).
We select product candidates for diseases and conditions that represent a significant unmet medical need, have well-understood biology and provide an opportunity to be first-to-market or offer a significant benefit over existing products. Based on this business model, it is easy to understand why BioMarin would have targeted a disease like MPS I for treatment. It is, as described, an orphan condition with a well-defined mechanism. Furthermore, before the development of Aldurazyme, there were no drugs to treat MPS I, allowing BioMarin to be first-to-market with its new pharmaceutical. Since the release of Aldurazyme, one more drug has been released to treat MPS; Elaprase is a treatment for MPS II. In 2016, Aldurazyme had an average cost-per-patient of $355,816. Collaboration between BioMarin and Genzyme
BioMarin/Genzyme is a 50/50 Limited Liability Company which co-owns the intellectual rights to Aldurazyme and works collaboratively on research and development. BioMarin is responsible for the production of Aldurazyme. It sells the finished product to Genzyme, which is a fully owned subsidiary of Sanofi. Genzyme pays a 39.5% - 50% royalty quarterly on worldwide net product sales to BioMarin. A portion of this royalty is considered to be product transfer royalties, meaning that if any Aldurazyme goes unsold, BioMarin merely retains the product transfer royalty, while not receiving any further royalties. Only in the case of defective product  is Genzyme reimbursed for Aldurazyme product. References
Further reading
External links
"Mucopolysaccharidosis type I". MedlinePlus. NBK1162. "Laronidase". Drug Information Portal. U.S. National Library of Medicine. Iduronidase at the US National Library of Medicine Medical Subject Headings (MeSH)