Currently, there is no effective treatment or cure for MPS III and treatment options are generally aimed at symptom management and supportive or palliative care.
The involvement of the brain in MPS III presents a special challenge in devising effective therapies. This is primarily because the brain is protected from the rest of the body by a barrier (the blood-brain barrier) that carefully controls what can and cannot enter the brain. This creates problems for treatments that are given via the bloodstream, such as enzyme replacement, for example (see below): the enzyme circulates throughout the body to treat the physical symptoms of the disorder but it does not readily enter the brain to stop the progressive decline in brain function. Researchers are therefore devising different methods by which to deliver enzyme to the brain, and progress is being made.
Several forms of treatment for MPS III have been tried or are in clinical trial. These include:
Haematopoietic Stem Cell Transplant (HSCT)
Bone marrow transplant and umbilical cord blood transplants are both forms of HSCT. The principle of HSCT is that cells taken from a healthy, unaffected donor (either bone marrow or cord blood) are transplanted into an affected person to produce normal amounts of the enzyme that is otherwise defective and thereby treat the disorder. The donor enzyme is not only produced within the transplanted cells but is also released by those cells into the circulation where it can be taken up by other cells in the body, including the brain.
HSCT has been used in children with MPS III but there is no evidence that it stops the decline in brain function and is therefore not recommended as a treatment. The reason(s) why it does not work in MPS III is not yet known.
Enzyme replacement therapy (ERT)
This form of therapy is based on the same principle as HSCT except that the missing enzyme (one of the four listed in What causes MPS III?) is replaced with a pharmaceutical-grade enzyme prepared commercially and given by infusion into the bloodstream rather than being produced inside the body by transplanted cells.
At the present time, ERT is not generally available for MPS III. However, a clinical trial is currently being conducted in patients with MPS III type A. Patients enrolled in this trial are receiving enzyme (in this case, sulphamidase) via injection directly into the cerebrospinal fluid (the fluid that surrounds the brain and spinal cord). To find out more about this trial visit www.clinicaltrials.gov [ID: NCT 01299727]
Gene therapy aims to replace the defective gene with a functional one. The principle is that the functional gene will code for the normal production of enzyme, reproduce within the cells of the body (and brain) and produce sufficient amounts of enzyme to remove stored mucopolysaccharide and prevent further storage. Unlike ERT, which requires repeated administration, it is hoped that gene therapy will be a once-off treatment. A clinical trial of gene therapy in patients with MPS III type A commenced in 2011. For further information about the trial, visit www.sanfilippo-syndrome.org/news/.
It is important to note that ERT and gene therapy specific for one form of MPS III will not work for the other three. This is because they are all caused by different enzyme deficiencies. Therefore, these forms of treatment will need to be developed independently for each of the four MPS III disorders.
Substrate Deprivation/Reduction Therapy
This aims to reduce the amount of mucopolysaccharide that is being made by the body, leading to a reduction in the amount being stored. Two clinical trials of this form of therapy have been trialled in MPS III patients. The first used a compound called Miglustat, which did not improve clinical symptoms and has not been recommended for use as a treatment for MPS III. The second compound tested is called genistein; the results have been inconclusive and further studies are needed. Further information on these trials can be obtained by visiting www.sanfilippo-syndrome.org/news/.
As a general rule, substrate deprivation/reduction therapy will only work in those individuals whose mutations allow some active enzyme to be made by the body.
In common with all of the MPS disorders, treatment and management for MPS III continue to evolve so the information presented here will change with time. It is important to keep up a regular dialogue with your medical team. Regular monitoring is an important way of managing problems before they become potentially serious, and to maximise quality of life. Living with a progressive disorder such as MPS III is difficult and challenging and this monitoring can also be a way to share some of that difficulty. As knowledge is built up and shared new treatments can be developed and quality of life improved for all..