Treatment options vary across the lysosomal storage disorders, and patients often undergo a variety of therapies and care. For most LSDs, no disease-specific therapy is available, and only palliative care--for example, dialysis, surgery, or physical therapy--can address clinical symptoms. These methods can be effective in managing symptoms, but they do not affect the biochemical cause of the disease.^[1] However, some LSDs do have disease-specific options, discussed below.

LSDs may affect multiple systems

LSD symptoms can affect nearly every bodily system (see the Presentation and Progression page), so treatment requires a multidisciplinary approach, with a lead physician (usually a geneticist) directing care and referring to other specialists as necessary.[1,2]

Disease-specific therapies may address the underlying enzyme and/or storage problem and are available for some of the LSDs. The three approaches to address lysosomal storage include:

Hematopoietic stem cell transplant (HSCT) - Healthy stem cells (usually from bone marrow, sometimes from cord blood)^[1] are transplanted intravenously to the patient to produce the enzyme as well as new healthy cells.

Enzyme replacement therapy (ERT) - A recombinant form of the deficient enzyme is administered intravenously.

Substrate inhibition - The rate of production of the substrate is slowed by drug therapy.

Bone marrow transplant was first attempted in the 1980s^[2] and has been most used to treat MPS I. Despite its challenges and risks (difficulty finding a good donor match; transplant failure or rejection;^[3] toxicity of the conditioning regimen^[1]) it has had some positive results, especially when performed early in a disease’s course.^[2] It has an increased chance for success with newborns, whose naturally suppressed immune systems lower the risk of transplant rejection.^[3]

Initial research on ERT began in the mid-1960s, and by the 1980s clinical trials were underway. In the early 1990s, advances in recombinant DNA manufacturing enabled enzyme production in quantities large enough for commercial development.^[2] The first ERT for Gaucher type I went on the market in 1991.^[2,3] ERT is a treatment option for Gaucher Type I, Fabry, and MPS I, with clinical investigations underway for Pompe, MPS II, and MPS VI.

Substrate inhibition has recently been introduced in 2002 for Gaucher Type I patients where ERT is not an option. Further clinical studies for substrate inhibition in Gaucher disease, Fabry disease, GM2-gangliosidoses (Tay-Sachs disease, Sandhoff disease, GM2 activator disease), and Niemann-Pick type C are in progress.

Both ERT and HSCT have limited efficacy on neurologic symptoms, since the large enzyme molecules introduced intravenously cannot penetrate the blood-brain barrier.^[1,2,3,4] ERT development continues to face challenges, such as difficulties targeting the affected cells. Today, neuronopathic LSDs are primarily managed palliatively, but new treatment modes are under development in this area:

Small molecule drugs can generally be administered orally^[2] and are small enough to cross the blood-brain barrier. They act as pharmacologic “chaperones”^[3] to enable:

Enzyme enhancement therapy, which attempts to stabilize faulty enzymes in LSDs caused by enzyme malfunctions (rather than total deficiency).^[3]

Substrate synthesis inhibition therapy, which attempts to block a step in the production of waste to minimize the amount of accumulation.^[?] It may be most effective in patients with some residual enzyme presence (rather than total deficiency) and as an adjunct to other treatments (such as ERT).^[2,4]

Gene therapy involves replacing the patient’s mutated gene with a normal copy so proper enzyme production can occur. Gene therapy is still only in preclinical (animal) studies, and much research is needed, especially in identifying appropriate vectors for gene delivery.^[2]

Disease registries (learn more at the Disease Registries page) are in place for many of the LSDs to help aggregate patient data, keep physicians up to date on clinical findings and care options, and fuel ongoing treatment research efforts.

1. Muenzer, J. The Mucopolysaccharidoses: A Heterogeneous Group of Disorders with Variable Pediatric Presentations. Journal of Pediatrics; May 2004: S27-S34.

2. Wilcox, WR. Lysosomal Storage Disorders: The Need for Better Pediatric Recognition and Comprehensive Care. Journal of Pediatrics; May 2004: S3-S14.

3. Desnick, RJ, Schuchman, EH. Enzyme Replacement and Enhancement Therapies: Lessons from Lysosomal Storage Disorders. Nature Reviews - Genetics. 2002; 3: 954-966.

4. Wenger, DA. Insights into the Diagnosis and Treatment of Lysosomal Storage Diseases. Arch Neurol; 60: 322-328.