How Do Pharmacologic Chaperones Work?

Pharmacological chaperones are a class of drugs used for treating Fabry disease.

Human cells have a compartment called the endoplasmic reticulum, responsible for the production and distribution of proteins. Faulty proteins are immediately destroyed in the endoplasmic reticulum as a part of a tight quality-control mechanism.

Fabry disease is a condition that occurs due to a mutation in the GLA genes. GLA genes provide instructions for producing an enzyme called alpha-galactosidase A. This enzyme has a major role in lysosomes—structures that act as recycling centers within cells. Lysosomes remove worn-out cell components and recycle usable parts with the help of digestive enzymes. Alpha-galactosidase A breaks down a molecule called globotriaosylceramide (Gb3) in the lysosome as a part of the natural mechanism. Mutation in GLA genes leads to the production of faulty alpha-galactosidase A. Faulty alpha-galactosidase A does not reach the lysosome to break down the Gb3 molecules, resulting in the accumulation of these molecules.

Pharmacological chaperones are small molecules that help proteins become functional by assisting them to take their ideal shape and remain stable. Chaperones help correct the alpha-galactosidase A, thereby delivering it to lysosomes to process excess Gb3 molecules.

Pharmacologic chaperones are used in the treatment of Fabry disease. Their use in Niemann-Pick disease type C is pending approval from the FDA.

Pharmacologic chaperones can cause the following side effects:

• Headaches
• Urinary tract infection
• Nausea
• Fever
• Abdominal pain
• Back pain
• Cough
• Diarrhea
• Epistaxis (nosebleed)

The information contained herein is not intended to cover all possible side effects, precautions, warnings, drug interactions, allergic reactions, or adverse effects. Check with your doctor or pharmacist to make sure these drugs do not cause any harm when you take them along with other medicines. Never stop taking your medication and never change your dose or frequency without consulting your doctor.

Generic and brand names of pharmacologic chaperones include:

• Arimoclomol
• Galafold
• Migalastat