Enzyme replacement therapy for Gaucher disease
Last updated April 30, 2025, by Marisa Wexler, MS
Fact-checked by Ines Martins, PhD
Enzyme replacement therapy (ERT) is a key treatment approach for Gaucher disease that addresses the disorder’s underlying cause.
Gaucher disease is a rare genetic disorder caused by a deficiency or absence of the enzyme glucocerebrosidase, known as GCase, which is needed to break down a fatty molecule called glucocerebroside, or Gb1. When GCase is deficient, Gb1 accumulates to harmful levels inside certain cells, ultimately driving Gaucher disease symptoms.
ERT works by supplying the body with a working version of GCase, essentially replacing the defective enzyme to restore the normal breakdown of Gb1.
It was the first class of therapies to gain widespread approval as a Gaucher disease treatment. Now used for more than three decades, these medications are designed to reduce Gb1 accumulation, helping to ease symptoms and slow the progression of Gaucher disease.
Another class of treatments, substrate reduction therapy, or SRT, is also approved for Gaucher. While SRT is taken orally, offering a more convenient alternative to the regular infusions required for ERT, enzyme replacement remains the preferred first-line treatment option for most people with Gaucher disease.
What is enzyme replacement therapy?
ERT is a treatment approach that’s mainly used for lysosomal storage disorders, a group of rare inherited diseases caused by missing or malfunctioning enzymes inside lysosomes. Lysosomes are cellular compartments that act like a molecular garbage disposal, breaking down old or unneeded molecules into smaller building blocks that cells can reuse.
There are many digestive enzymes inside lysosomes, each responsible for degrading specific molecules. If an enzyme is missing or defective, the molecule it would normally break down instead accumulates to toxic levels, causing damage.
The overarching idea behind ERT for lysosomal storage disorders is to deliver a functional version of the missing enzyme into the bloodstream, which can then be picked up by affected cells. Once inside cells, the enzyme can help facilitate the breakdown of the excess molecules, reducing their harmful effects and slowing or stopping disease progression.
Enzyme replacement therapy for Gaucher disease
In Gaucher, mutations in the GBA1 gene impair the production and/or function of the lysosomal enzyme GCase. The goal of ERT for Gaucher disease is to address this GCase deficiency by delivering a functional version of the enzyme to cells. This helps facilitate the clearance of Gb1, which is expected to ease symptoms, slow disease progression, and prevent more serious complications.
ERT is generally effective at managing many of the symptoms of Gaucher disease, including an enlarged liver and spleen, bone disease, and blood-related issues. It is most beneficial when started early, as it can help to prevent long-term complications and improve quality of life.
For that reason, ERT is considered a mainstay of Gaucher disease management and is often started shortly after a Gaucher disease diagnosis, with treatment typically continuing throughout a person’s life.
ERT is especially effective for Gaucher disease type 1, the most common type of Gaucher disease, which is defined by the absence of neurological complications. In these patients, treatment should be started as soon as signs or symptoms indicative of the disease appear.
However, because available ERTs cannot cross the blood-brain-barrier, which controls which substances in the bloodstream can pass into the brain and spinal cord, they are not effective at managing the neurological symptoms seen in Gaucher disease types 2 and 3. These therapies may still be used to address non-neurological problems in Gaucher type 3, but offer little to no benefit for people with type 2.
Available enzyme replacement therapies for Gaucher disease
Three ERTs are approved by the U.S. Food and Drug Administration (FDA) for the treatment of Gaucher disease. All are administered via regular intravenous, or into-the-vein, infusions, and are specifically indicated for people with Gaucher disease type 1. They are:
Cerezyme
Cerezyme, marketed by Sanofi, was the first recombinant, or lab-made, treatment to be approved for Gaucher disease. It received clearance in 1994, replacing Ceredase, which had been introduced in 1991 but relied on enzyme extraction from donated human placental tissue.
The therapy is approved in the U.S. for adults and children ages 2 and older with Gaucher disease type 1 who experience symptoms such as low red blood cell or platelet counts, bone disease, or enlargement of the spleen or liver. In the European Union and Canada, it’s also approved for managing non-neurological symptoms of Gaucher disease type 3.
Cerezyme is administered via intravenous infusions, at a dose and frequency that are tailored to individual patient needs.
VPRIV
VPRIV, sold by Takeda Pharmaceuticals, is another recombinant, FDA-approved enzyme replacement therapy option that became available in 2010. It is indicated for the long-term treatment of children and adults with type 1 Gaucher disease. VPRIV is administered once every two weeks.
Elelyso
Elelyso, developed by Protalix Therapeutics in collaboration with Pfizer, was approved in the U.S. in 2012. for treating Gaucher disease type 1 in adults and children ages 4 and older. It is given via intravenous infusion every other week.
While the enzymes in other ERTs are produced using mammalian cells, Elelyso is notably the only ERT that is made by plant cells, namely carrot cells. This makes it inherently more effective at reaching and entering the affected cells in people with Gaucher.
Potential side effects or complications
As with any treatment, Gaucher disease ERT carries certain benefits as well as potential risks and safety concerns, although it usually has fewer negative side effects compared with SRT.
Side effects that may occur due to ERT include:
- pain in the abdomen, back, extremities, and/or joints
- fatigue or weakness
- headache
- fever
- nausea and vomiting
- dizziness
- chills
- flushing
- itching
- hives
- blood-clotting issues.
In some cases, ERT can also cause allergic reactions. All of these available medications carry a boxed warning for potentially life-threatening allergic reactions, including anaphylaxis. For that reason, they must be administered under the supervision of a healthcare provider trained in managing these reactions and in a healthcare setting with appropriate medical monitoring and emergency support.
Some patients may also develop antibodies against the delivered enzyme, which are considered risk factors for severe allergic reactions.
Gaucher Disease News is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.
