Enzyme replacement therapy

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 Alglucerase. ERTs were initially manufactured by isolating the therapeutic enzyme from human placenta. The FDA has approved ERTs that are derived from other human cells, animal cells (i.e. Chinese hamster ovary cells, or CHO cells), and plant cells. == Medical uses ==

Lysosomal storage diseases are a 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. This is a fatal childhood disease that requires early medical intervention. When the enzyme adenosine deaminase is deficient in the body, the result is a toxic build-up of metabolites that impair lymphocyte development and function. Many ADA deficient children with SCID have been treated with the polyethylene glycol-conjugated adenosine deaminase (PEG-ADA) enzyme. This is a form of ERT that has resulted in healthier, longer lives for patients with ADA-SCID. == Administration ==

ERT is administered by IV infusion. Typically, infusions occur every week or every two weeks. For some types of ERT, these infusions can occur as infrequently as every four weeks. == Complications ==

ERT is not a cure for lysosomal storage diseases, and it requires lifelong IV infusions of the therapeutic enzyme. In addition to this, treatment requires frequent infusions that can last several hours and must be administered on a regular basis, which can create ongoing time and logistical burdens for patients. The distribution of the therapeutic enzyme in the body (biodistribution) after these IV infusions is not uniform. The enzyme in less available to certain areas in the body, like the bones, lungs, brain. For this reason, many symptoms of lysosomal storage diseases remain untreated by ERT, especially neurological symptoms. Additionally, the efficacy of ERT is often reduced due to an unwanted immune response against the enzyme, which prevents metabolic function. == Other treatments for enzyme deficiencies ==

Substrate reduction therapy is another method for treating lysosomal storage diseases. In gene therapy, a gene encoding for a certain protein is inserted into a vector. These cells have the ability to mature into the many cell types that comprise blood, including red blood cells, platelets, and white blood cells. This treatment is often used to treat the central nervous system of patients with some lysosomal storage diseases. == See also ==