Enzyme replacement therapy
(Redirected from Pegademase)
Enzyme Replacement Therapy (ERT) is a medical treatment approach targeting congenital enzyme deficiencies. It makes use of purified enzyme preparations sourced from human, animal, or recombinant (genetically engineered) origins. These preparations are typically administered parenterally, most commonly via intravenous infusion.
Indications[edit | edit source]
The primary candidates for ERT are individuals with rare genetic disorders that cause severe disabilities and increase the risk of premature mortality.
Mechanism of Action[edit | edit source]
ERT serves to compensate for the absence or inadequacy of a particular enzyme in individuals suffering from inherited enzyme deficiency syndromes. The therapy introduces an externally sourced enzyme, either harvested from human or animal tissues/blood or synthesized through recombinant methods. Often, the introduced enzyme undergoes modifications to enhance its half-life, improve its potency, increase its resistance to degradation, or to target a specific organ, tissue, or cellular structure.
Examples of ERT[edit | edit source]
Alpha-1-Antitrypsin deficiency: The earliest success stories in ERT pertained to A1AT deficiency, which was treated using purified human A1AT derived from plasma. This deficiency, leading to early-onset emphysema, results from a lack of leukocyte elastase inhibitor, causing continuous pulmonary damage. The therapy demonstrated its efficacy, especially among patients showing early or intermediate pulmonary dysfunction signs. Notably, no instances of viral hepatitis were reported, even though the therapy derived from human plasma.
Gaucher disease: Gaucher disease arises from an inherited deficiency of lysosomal acid β-glucocerebrosidase. This leads to substrate buildup (like glucocerebroside) within lysosomes. The primary affected areas are the liver, spleen, and bone. Initial treatments employed glucocerebrosidase extracted from placental tissue, modified for macrophage-specific uptake and lysosome delivery. However, the current standard employs recombinant forms of glucocerebrosidase for treating type 1 Gaucher disease.
Other Genetic Conditions Treated with ERT[edit | edit source]
ERT has expanded to address multiple enzyme deficiency syndromes. Some notable diseases include:
- Adenosine deaminase deficiency
- Lysosomal acid lipase deficiency
- Fabry disease
- Pompe disease
- Hurler syndrome
- Hunter syndrome
Other rare mucopolysaccharidoses forms A comprehensive table enumerating approved enzymes for ERT in the U.S. – including their first approval year, generic and brand names, and the associated disease – provides an overview of its widespread applications.
Side Effects[edit | edit source]
While most patients tolerate both natural purified and recombinant enzymes, potential side effects include:
- Localized infusion reactions
- Hypersensitivity responses, which may manifest as rash, fever, hypotension, bronchospasm, angioneurotic edema, anaphylaxis, or even cardio-pulmonary collapse.
It's noteworthy that hypersensitivity reactions are generally more severe in patients completely lacking the enzyme. Mild reactions often subside over time and may be preventable through premedication with antipyretics, antihistamines, or corticosteroids.
List of Enzyme replacement therapy[edit source]
Generic Name | Brand Name | Enzyme | Year | Disease |
---|---|---|---|---|
Alpha1-Proteinase inhibitor | Prolastin-C Glassia | Alpha1-Antitrypsin | 2009/2010 | A1AT Deficiency |
Alglucerase alfa | Ceredase* | β-Glucocerebrosidase | 1991 | Gaucher |
Imiglucerase | Cerezyme | β-Glucocerebrosidase | 1995 | Gaucher |
Taliglucerase alfa | Elelyso | β-Glucocerebrosidase | 2012 | Gaucher |
Velaglucerase alfa | VPRIV | β-Glucocerebrosidase | 2010 | Gaucher |
Pegademase | Adagen | Adenosine Deaminase | 2000 | ADA Deficiency |
Agalsidase beta | Fabrazyme | Alpha-Galactosidase A | 2003 | Fabry |
Alglucosidase alfa | Lumizyme | Acid alpha-Glucosidase | 2010 | Pompe |
Laronidase | Aldurazyme | α-L-Iduronidase | 2003 | Hurler, MPS I |
Idursulfase | Elaprase | Iduronate-2-Sulfatase | 2006 | Hunter, MPS II |
Elosulfase alfa | Vimizim | N-Acetylgalactosamine-6 Sulfatase | 2014 | Morquio Snydrome A, MPS IVA |
Galsulfase | Naglazyme | N-Acetylgalactosamine-4 Sulfatase | 2005 | Maroteaux-Lamy, MPS VI |
Sebelipase alfa | Kanuma | Lysosomal Acid Lipase | 2015 | Wolman, LAL Deficiency |
* Withdrawn from market. MPS=Mucopolysaccharidosis.
genetic disorder agents[edit source]
- gaucher disease agents
- glucocerebrosidase (enzyme replacement therapy)
- imiglucerase, taliglucerase alfa, velaglucerase alfa
glucosylceramide synthase inhibitors (substrate restriction therapy)
lysosomal acid lipase deficiency agents
miscellaneous
- agalsidase beta, alglucosidase alfa, alpha1-proteinase inhibitor, elosulfase alfa, galsulfase, idursulfase, laronidase, pegademase
homocystinuria agents
Huntington disease agents
- Vesicular Monoamine Transporter 2 (VMAT2) Inhibitors
Tyrosinemia Agents
Urea Cycle Disorder Agents
Hematologic Agents
Enzyme replacement therapy Resources | ||
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Contributors: Prab R. Tumpati, MD