Product case study Aldurazyme

Aldurazyme (tradename, also known as laronidase) is a recombinant version of one polymorphic variant of the human enzyme a-l-iduronidase. It was approved for general medical use in the USA in 2003 and is indicated for the treatment of patients with certain forms of the rare inherited disease MPS I. MPS I is caused by a deficiency of a lysosomal a-l-iduronidase, which normally catalyses the hydrolysis of terminal a-l-iduronic acid residues from the glycosaminoglycans der-matan sulfate and heparin sulfate. The deficiency results in accumulation of the glycosaminogly-cans throughout the body, causing widespread cell and tissue dysfunction.

The 628 amino acid, 83 kDa monomeric glycosylated enzyme containing six N-linked oligosaccharide side-chains is produced in an engineered CHO cell line. After cell culture it is purified by a combination of dye affinity, metal chelate and hydrophobic interaction chroma-tography. The final product is formulated as a liquid concentrate containing laronidase, as well as sodium phosphate buffer, sodium chloride and polysorbate 80. It is filled in 5 ml single-use vials and is usually administered intravenously by infusion (0.58 mg per kilogram body weight) over 3-4 h, once weekly. Fortuitously, two of the enzyme's oligosaccharide side-chains terminate in mannose-6-phosphate, facilitating product cellular uptake via the mannose-6-phosphate cell surface receptor.

Clinical evaluation entailed administration to 45 MPS I patients in a randomized, placebo-controlled clinical trial. The primary efficacy outcomes assessed were forced vital capacity and distance walked in 6 min, both of which were statistically higher relative to placebo after 26 weeks of treatment. The most serious adverse reaction noted was that of a severe anaphylactic reaction in one patient. The most common adverse effects reported were respiratory tract infection, rash and injection-site reactions. The product is manufactured by BioMarin Inc. and is distributed by Genzyme Corporation.

from cultures of the fungus Aspergillus flavus has been used to treat this condition for a number of years. More recently, a recombinant form of the fungal enzyme (tradename Fasturtec) has gained regulatory approval in the EU. Produced in an engineered strain of S. cerevisiae, the enzyme is a tetramer composed of four identical polypeptide subunits. Each subunit contains 301 amino acids, displays a molecular mass of 34 kDa and is N-terminal acetylated.

Laronidase is yet an additional recombinant enzyme now approved for general medical use. The product, used to treat mucopolysaccharidosis, is overviewed in Box 12.2.

Supplements For Diabetics

Supplements For Diabetics

All you need is a proper diet of fresh fruits and vegetables and get plenty of exercise and you'll be fine. Ever heard those words from your doctor? If that's all heshe recommends then you're missing out an important ingredient for health that he's not telling you. Fact is that you can adhere to the strictest diet, watch everything you eat and get the exercise of amarathon runner and still come down with diabetic complications. Diet, exercise and standard drug treatments simply aren't enough to help keep your diabetes under control.

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