Substrate reduction therapy is one possible treatment for Gaucher disease. It is sometimes used in combination with enzyme replacement therapy.
What is Gaucher disease?
Gaucher disease is a rare heritable disease that affects several body systems and causes symptoms that vary widely among patients.
The disease is caused by mutations in the GBA gene, which contains the instructions to make an enzyme called beta-glucocerebrosidase. This enzyme is involved in breaking down a component of cell membranes called glucocerebroside.
Mutations in the gene cause the enzyme to be made incorrectly, which means that when cells try to break down pieces of cell membranes, there is a buildup of toxic waste products. Over time, these waste products poison the cell, causing the symptoms of the disease.
GBA is active in many different cell types, so depending on which cells are affected, the symptoms may be very different among patients.
What is substrate reduction therapy?
Substrate reduction therapy uses small molecules that inhibit the synthesis of the cell membrane component that is broken down by beta-glucocerebrosidase. By reducing the substrate of the enzyme, the levels of the waste products can be reduced.
Substrate reduction therapy can be used in combination with enzyme replacement therapy — a treatment that supplies artificially produced, active enzyme to a patient’s body.
There are two substrate reduction therapies approved by the U.S. Food and Drug Administration (FDA) for the treatment of Gaucher disease:
Cerdelga (eliglustat) is the first-line treatment for adults with type 1 Gaucher disease, and is considered suitable for long-term treatment.
Zavesca (miglustat) is only used in patients with mild to moderate type 1 Gaucher disease who cannot be treated with enzyme replacement therapy.
Substrate reduction therapy can cause side effects such as fatigue, headache, nausea, diarrhea, back pain, pain in extremities, and upper abdominal pain.