Fabry disease is a life limiting condition and patients have to take treatment throughout their lives - irrespective of whether it is treating the signs and symptoms of disease or managing the underlying metabolic defect.
Broadly speaking, there are currently two complementary approaches to the management of Fabry: 1) Treatment of the metabolic defect, using enzyme replacement therapy (ERT) and 2) chaperone therapy symptomatic treatment of disease symptoms
Enzyme replacement therapy ERT is the standard treatment for Fabry disease. ERT offered the first opportunity to treat the underlying enzyme deficiency. Considered the standard treatment for Fabry disease, ERT provides an exogenous source of α-galactosidase (α-Gal) A, replacing the deficient enzyme in the body’s cells, thus helping to slow disease progression.
Chaperone therapy Some α-Gal A gene mutations (termed ‘amenable mutations’) can lead to misfolded α-Gal A variants that have residual enzyme activity but are unstable. This results in impaired delivery of the enzyme into lysosomes and misassembled or aggregated enzyme in the endoplasmic reticulum, leading to a loss of or reduction in enzyme function. These variants may be stabilized by chemical chaperones, which bind to the enzyme’s active site to promote correct folding and trafficking of endogenous α-Gal A. Chaperone therapy is administered orally and is only feasible and approved for patients with an amenable mutation.
- Symptomatic treatment of Fabry disease requires a multidisciplinary approach as a result of the varied nature of symptoms; multiple, concomitant treatments are therefore usually necessary. Organ function, symptom control and psychosocial aspects of the condition all require consideration.