Enzyme replacement therapy

From WikiMD's Wellness Encyclopedia

(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:

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]

cystic fibrosis agents

enzyme replacement therapy

glucosylceramide synthase inhibitors (substrate restriction therapy)

lysosomal acid lipase deficiency agents

miscellaneous

homocystinuria agents

Huntington disease agents

Monoclonal Antibodies

Tyrosinemia Agents

Urea Cycle Disorder Agents

Hematologic Agents

Enzyme replacement therapy Resources

Contributors: Prab R. Tumpati, MD