The goals of managing MPS II are to improve quality of life, slow down its progression, and to prevent permanent tissue and organ damage. Early intervention may help prevent irreversible damage.
The involvement of the brain in some people with MPS II presents a special challenge in devising effective therapy. This is primarily because the brain is protected from the rest of the body by a barrier (the blood-brain barrier) that 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 II are in use. These include:
Haematopoietic Stem Cell Transplant (HSCT)
Bone marrow transplant (BMT) and umbilical cord blood transplant are both forms of HSCT.
BMT involves the reduction or removal of an affected person’s bone marrow and replacing it with bone marrow cells from an appropriate tissue-matched donor who is not affected by the same condition. This donor may be a family member or an unrelated donor from a bone marrow donor panel. It can take a considerable amount of time to find a suitable donor match.
Umbilical cord blood transplant is based on the same principle as BMT but involves taking stem cells that are found in umbilical cord blood. Cord blood is collected from the afterbirths (placenta) of newborn babies (with parental consent). The baby donors are not normally related to the patient although the cord blood needs to be a suitable match for it to be considered. In all other aspects the two procedures are the same.
The principle of HSCT is that the donor cells (cord blood or bone marrow) will reproduce (or replicate) within the affected person to produce normal amounts of enzyme (2-sulphatase in the case of MPS II) to treat the disorder: the 2-sulphatase 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 of the body.
In contrast to people with cancers (where HSCT is regularly used) in the case of MPS II it is not necessary to completely remove the individual’s own bone marrow; the level of marrow reduction must be sufficient enough to allow room for the new bone marrow cells to establish and grow. A treatment necessary to reduce a person’s own marrow (known as ‘conditioning’) is used to minimise the risk of the transplant procedure. It is important to understand, however, that HSCT in all its forms is an extensive procedure that may require quite a long stay in hospital. There are still significant risks involved with these procedures, including infection, graft vs. host disease and other complications which may be life-threatening.
There is no published evidence that HSCT improves intellectual outcomes in MPS II if the brain is affected. The reason(s) for this is not known.
HSCT has been shown to have a positive outcome in altering the progression of MPS II and improving life expectancy in those whose brain is not affected. Many of the physical features (harshness of facial features, hearing, enlarged liver and spleen, and heart function) may also improve following transplant. However, HSCT has less effect on skeletal structure, and problems such as joint stiffness and pain, carpal tunnel syndrome and compression of the spinal cord can still occur. Considerable long-term physical, medical, surgical and psychological supportive care is necessary after successful HSCT.
In view of the risks, HSCT is not usually recommended as the first choice treatment for those with MPS II whose brain is not affected. However, it may be considered where other forms of treatment are not available or considered inappropriate on medical grounds, or where the risks of the treatment are higher than the transplant procedure.
Enzyme replacement therapy (ERT)
Following extensive clinical trials ERT is now the treatment of choice for most individuals with MPS II whose brain is not affected by the disorder. This therapy is based on the same principle as HSCT except that the missing enzyme (2-sulphatase) 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. The advantages of ERT over HSCT are that (i) the problems and long-term risks associated with transplantation are avoided; (ii) there is no need to find a suitable donor; and (iii) there is no need for ’conditioning’. However, many of the same advantages and limitations apply: for example, the earlier ERT is commenced the better the outcome but skeletal and related problems can still develop.
The commercial name of the enzyme preparation for MPS II is called Elaprase. People with MPS II who have received ERT over the last six or so years, have shown that it is safely tolerated. With the reduction in mucopolysaccharide storage resulting from ERT, sustained improvements have been demonstrated in endurance, walking and stair-climbing ability, joint mobility, lung function, growth and puberty. Marked improvements have also been noted in certain characteristics such as softening of the hair and facial features, and sometimes improved growth. Individuals have also noticed that their tummies are far less prominent due to the reduced liver and spleen size. However, whilst these improvements have contributed to better quality of life, patients usually continue to require physical, medical and surgical supportive therapy alongside ERT in the longer term.
ERT is not a cure and for it to be effective it needs to be given regularly during the person’s life. Currently, this is usually on a weekly basis. Infusions are usually given slowly over several hours to minimise the risk of reactions to the introduced enzyme. In Australia, infusions are usually done in a hospital setting.
In Australia, ERT is currently funded under the Commonwealth Government Lifesaving Drugs Program (LSDP) for people whose brain is not affected by MPS II.
Because ERT does not prevent the decline in brain function if given via the bloodstream (and is therefore not considered ‘life-saving’) it has not been funded for use in those whose brain is affected. If there is uncertainty about whether an individual’s brain is affected, ERT may be approved for use until it becomes clear. Further information is available through the LSDP website (www.health.gov.au/lsdp) and should be discussed with your medical team..