Enzyme replacement therapy

Enzyme replacement therapy (ERT) is a medical treatment which replaces an enzyme that is deficient or absent in the body. Usually, this is done by giving the patient an intravenous (IV) infusion of a solution containing the enzyme.

ERT is currently available for some lysosomal storage diseases: Gaucher disease, Fabry disease, MPS I, MPS II (Hunter syndrome), MPS VI and Pompe disease. ERT does not correct the underlying genetic defect, but it increases the concentration of the enzyme that the patient is lacking. ERT has also been used to treat patients with severe combined immunodeficiency (SCID) resulting from an adenosine deaminase deficiency (ADA-SCID).

Other treatment options for patients with enzyme or protein deficiencies include substrate reduction therapy, gene therapy, and bone-marrow derived stem cell transplantation.[1]

ERT was developed in 1964 by Christian de Duve and Roscoe Brady. Leading work was done on this subject at the Department of Physiology at the University of Alberta by Mark J. Poznansky and Damyanti Bhardwaj, where a model for enzyme therapy was developed using rats. ERT was not used in clinical practice until 1991, after the FDA gave orphan drug approval for the treatment of Gaucher disease with imiglucerase. ERTs were initially manufactured by isolating the therapeutic enzyme from human placenta. The FDA has now approved ERTs that are derived from other human cells, animal cells (i.e Chinese hamster ovary cells, or CHO cells), and plant cells.

Lysosomal storage diseases are fatal group of diseases and a main application of ERT. Lysosomes are cellular organelles that are responsible for the metabolism of many different macromolecules and proteins. They use enzymes to break down macromolecules, which are recycled or disposed. As of 2012, there are 50 lysosomal storage diseases, and more are still being discovered. These disorders arise because of genetic mutations that prevent the production of certain enzymes used in the lysosomes. The missing enzyme often leads to a build-up of the substrate within the body. This can result in a variety of symptoms, many of which are severe and can affect the skeleton, brain, skin, heart, and the central nervous system. Increasing the concentration of the missing enzyme within the body has been shown to improve the body's normal cellular metabolic processes and reduce substrate concentration in the body.

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