What Are the Types of MPS?
People with a mucopolysaccharidosis either do not produce enough of one of the 11 enzymes required to break down mucopolysaccharides (long chains of sugar molecules) into proteins and simpler molecules, or they produce enzymes that do not work properly. There are many different types of MPS syndromes, each one caused by a distinct, inherited enzyme deficiency. Upon birth, a child with MPS appears normal and will seem to develop normally for the first year or more, depending on the type of MPS they have.
The first signs can vary and are evident at different ages in affected children. Symptoms that usually prompt medical attention include frequent ear infections, runny noses, and colds.
Different types of MPS will present different characteristics:
How Is MPS Treated?
Currently, there is no cure for mucopolysaccharidosis (MPS) but treatments can help make the disease more manageable. The components for treatment are to alleviate specific symptoms of disease and to try and replace the enzyme that is missing.
Treatment recommendations for MPS varies depending on the syndrome type, clinical severity, present clinical signs and symptoms, age of the affected individual, and risks and benefits with available therapies. Treatment requires coordination of a multi-disciplinary team of specialists including surgeons, pediatricians, surgeons, cardiologists, audiologists, ophthalmologists, orthopedists, and other healthcare professionals.
Enzyme replacement therapy (ERT) and Hematopoietic stem cell transplantation (HSCT) and are the two main care therapies for MPS.
Enzyme Replacement Therapy (ERT) for MPS
Enzyme Replacement Therapy (ERT) is a medical treatment to replace an enzyme that is missing or present in abnormally lower amounts in the body. ERT does not cure the disease but slows its progress by increasing the amount of missing enzyme in the body.
The replacement enzyme is injected intravenously (through the blood vessels) into the body, on a regular schedule. These replacement enzymes are designed to perform the function of the defective enzyme and reduce the accumulation of “glycosaminoglycans” (GAGs) which are the long chains of complex sugar molecules that the MPS patient’s body cannot break down.
ERT is currently available for MPS I, MPS II, MPS IVA, MPS VI and MPS VII.
Find out more on specific ERT treatments for each MPS type by clicking on the icons above.
Hematopoietic Stem Cell Transplantation (HSCT) for MPS
Another method to replace the enzyme in patients is to perform hematopoietic stem cell transplantation (HSCT). With HSCT, healthy donor stem cells are transplanted that produce healthy blood cells and sufficient levels of white blood cells that produce the enzyme that is deficient in the tissues. The enzyme secreted by donor cells is then up taken by the recipient’s body through cross-correction. Recipients of HSCT can acquire donor cells from three different sources: bone marrow, peripheral blood, or umbilical cord blood.
The first stem cell transplantation on an MPS I patient was in 1981; a bone marrow transplantation (BMT) was performed on a 1-year old boy with MPS type I (Hurler syndrome).
View the Historical Timelines for MPS and Treatments >
Some of the advantages of HSCT include that it is generally a one-time procedure which allows the recipient to have a continuous source of enzyme, as well as rapid clearance of GAGs. With HCST, physical development may improve, cloudy corneas may become clear, the size of an abnormally enlarged liver and spleen may decrease, and mucopolysaccharide levels may drop. However, there is no change in skeletal malformations. The effect on neurological symptoms varies considerably.
Peripheral blood stem cell transplant (PBSCT) has significantly replaced the role of bone marrow transplant (BMT) in adolescent patients, due to the simplicity of donor collection associated with fewer complications and better outcomes. However, bone marrow is still the preferred donor source for adult patients because there is less incidence of Graft Versus Host Disease, (GvHD) where the donated bone marrow or blood stem cells view the recipient’s body as foreign, and the donated cells/bone marrow attack the body. Additionally, unrelated cord blood (UCB) is a source of donor cells due to its feasible and fast retrieval, and it decreases complications with immune tolerance.
Stem cell transplantation is a time-consuming process, and it can be challenging to find an acceptable donor for the transplantation. It is a procedure that carries significant risks and should only be considered in selected cases.
Investigational Therapies for MPS
Unfortunately enzyme replacement therapy does not help with symptoms related to brain damage and central nervous system because the medication cannot cross the blood-brain barrier (the protective network of blood vessels and cells that filters materials). HSCT is effective in treating neurological symptoms; however, this therapy requires the patient to undergo chemotherapy to eliminate their own stem cells before receiving the foreign, healthy stem cells.
As both of these treatment options have significant disadvantages, investigational gene and cell therapies for MPS are being researched in clinical trials to find better ways to replace the missing enzyme. These investigations include different forms of enzymes that may be able to access tissues better and gene-based therapies that could replace the missing enzyme.
In gene therapy a working version of a gene is introduced into the cells in charge of creating key proteins or enzymes. The patient is then able to produce the active enzyme thus preventing the development and progression of the disease. This form of therapy is theoretically most likely to lead to a “cure,” but technical challenges still need to be overcome before gene therapy can be advocated as a viable alternative approach.
Researchers are also exploring approaches for MPS using gene editing to correct enzyme production. The goal of gene editing is to remove, disrupt, or correct faulty elements of DNA within the gene rather than to introduce a functioning gene as gene replacement therapy would. There are no approved gene editing treatments yet, but there are some currently being researched in clinical trials.
MPS patients may consider participating in clinical trials for gene therapy. These trials offer an opportunity to receive an investigational treatment at no cost, while also benefiting the medical community and others who have the disease. Eligibility, risks, and benefits should be discussed with the individual’s disease specialist or primary provider.
For more information about active clinical studies view our Clinical Trials page.