Treatment of mucopolysaccharidosis type III (Sanfilippo syndrome)

Abstract

Introduction: Mucopolysaccharidosis type III (MPS III or Sanfilippo syndrome or Sanfilippo disease) is caused by a deficiency in one of four enzymes involved in heparan sulfate (HS) degradation, leading to lysosomal HS accumulation. MPS III is characterized by severe central nervous system (CNS) disease, leading to progressive neurocognitive deterioration. Patients show a broad spectrum of disease progression and severity. To date, no disease modifying treatment is available for MPS III.

Areas covered: An overview of the different pathophysiological mechanisms involved in MPS III is presented. We discuss the different therapies for MPS III which are currently being investigated, either in animal models or in clinical trials and the advantages and limitations of each therapeutic approach.

Expert opinion: The blood–brain barrier (BBB) is the bottleneck in the development of drugs for MPS III and a number of very promising approaches to target the BBB are currently studied. To assess the full therapeutic potentials of any drug or combination of drugs, trials including very early diagnosed or even fully asymptomatic patients in combination with information on the natural history of the disease are necessary. However, almost all MPS III patients are diagnosed because of developmental delay with behavioral difficulties. At that time substantial and irreversible damage to the central nervous system (CNS) may already be present. In the best case scenario, disease-modifying therapy may only halt disease progression. Early diagnosis and initiation of treatment are therefore essential. This will only be feasible through family screening and perinatal diagnosis of patients' siblings or, in the general population, via newborn screening.

Keywords::

• mucopolysaccharidosis type III
• Sanfilippo syndrome
• therapy
• treatment

Notes

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