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Mucopolysaccharidoses (MPS) represent a heterogeneous group of genetic lysosomal storage disorders caused by the deficiency of enzymes catalyzing the degradation of glycosaminoglycans (previously known as mucopolysaccharides). This leads to accumulation of glycosaminoglycans in the lysosomes of most cells, resulting in cell, tissue and organ dysfunction.
The first successful treatment for mucopolysaccharidoses was bone marrow transplantation, which was introduced for the therapy in 1980. Over the last decade a panoply of different therapeutic approaches has either become available or is currently in development to address this disease.
Before the advent of therapies targeting the deficient enzyme activity, the treatment of mucopolysaccharidosis was predominantly focused on the prevention and care of complications, which still represents a very important aspect in the management of these patients.
Due to a large number of comorbidities that need to be addressed, a whole team of specialists such as orthopedic surgeons, neurosurgeons, cardiologists, pneumologists, ophtalmologists, otorhinolaryngologists and physiotherapists are required when approaching these rare conditions.
Many complications of mucopolysaccharidoses require surgery, although its burden is often very high for patients with severe somatic involvement. These include common interventions such as hernia repair, orthopedic surgery for joint contractures and skeletal deformities, carpal tunnel release operation, corneal transplants and adenotonsillectomy.
Due to the complexity and rarity of these disorders, as well as high risk of anesthetic and surgical complications, individuals with this disease should be monitored and treated at a facility with an expertise in treating patients with mucopolysacchardioses.
Hematopoietic stem cell transplantation (HSCT) has been used in patients with mucopolysaccharidosis in order to correct the enzyme-deficiency. Although it is considered to be a high-risk procedure with a high morbidity and mortality rate, various studies show that it can change the natural history of the disease, increase life expectancy and improve many systemic abnormalities.
The treatment consists of transplanting stem cells from the blood of a healthy donor into the body of the affected individual. If the procedure works, the donated cells begin to multiply and produce all the enzymes they produced in the donor – including the one that the transplant recipient was lacking. HSCT should be done as early as possible, i.e. before significant accumulations have developed in the brain.
Following the success of enzyme replacement therapy (ERT) for the treatment of Gaucher disease (another type of lysosomal storage disorder), this method was also developed for mucopolysaccharidosis. The treatment involves regular-infusions of a recombinant product which is similar to the deficient enzyme missing in the specific type of the disease.
ERT represents a life-long therapy, and each infusion takes from one to four hours, depending on the enzyme and the dose. Up to one half of all patients can initially experience reactions such as flushing, headache and fever, but potentially life-threatening anaphylaxis can also occur in some patients receiving ERT.
Over the last decade a whole new set of therapeutic measures have become available or are currently in the development. Those emerging treatment options include substrate inhibition therapy using small molecules which cross the blood–brain barrier, the use of chaperones, stop-codon read-through strategy, gene therapy and the use of neural stem cells.
It is important to specify that all mucopolysaccharidoses are hard to treat and demand specific therapies with a broad range of supportive measures. An additional challenge is a high cost of these technology intensive approaches, which needs to be addressed if the treatments are to become even more entrenched in the clinical routine.