Common hereditary lysosomal storage diseases

The outlook for patients has improved dramatically for these diverse disorders. Orphan drug legislation in Europe and the US makes it financially attractive to companies to develop medications for patients with rare diseases by granting market exclusivity and extended patent protection. However, major areas of unmet need remain. Current treatment approaches are extremely expensive, and there is debate about cost-effectiveness. Most available treatments do not access the central nervous system (CNS).

Tissue distribution of enzyme replacement therapy (ERT) is limited, and whereas ERT is extremely effective for the visceral and bone marrow manifestations of Gaucher disease, it is less effective for the skeletal manifestations. Treatment of Fabry disease and Pompe disease is more challenging, as is ERT for the mucopolysaccharidosis disorders.

Antibody formation is likely to reduce the effectiveness of ERT. Data for Gaucher disease show little impact of enzymes on ERT effectiveness. Antibodies are likely to affect efficacy of ERT in Pompe disease. Studies are under way for the other lysosomal storage diseases (LSDs).

Gaucher disease

Type 1 Gaucher disease is amenable to ERT and life expectancy is improved. Substrate reduction therapy is suitable for less severely affected patients with type 1 disease who are unable to tolerate intravenous therapy, or who are allergic to available enzyme replacement therapy preparations. Type 2 remains essentially untreatable. Type 3 is clinically diverse and the non-CNS aspects of the disease respond well to ERT. Cheaper ERT will allow expanded access across the globe. Chaperone and gene therapy approaches are being explored.

Fabry disease

ERT has made a substantial impact in the treatment of men, women, and children. It is likely that life expectancy is improved as ERT improves function of critical organs (e.g., kidney, heart). However, ERT does not reverse severe organ damage and there are questions over when to start treatment, dose, and impact of antibodies.

Pompe disease

ERT extends the life of sufferers, particularly neonates. Antibody formation may be reduced with novel approaches at desensitisation.

Other LSDs

Although there is a greatly improved outlook for other LSDs, challenges remain. Many continue to be untreatable, and supportive care is important. Access to drugs, earlier diagnosis, and raising awareness among physicians are other challenges.