Hematopoietic stem cell transplant for the mucopolysaccharidoses

Introduction: The mucopolysaccharidoses (MPS) are a group of rare lysosomal storage diseases arising from a deficiency in the enzymes that breakdown glycosaminoglycans. They are characterised biochemically by substrate accumulation and clinically by multi-organ dysfunction and premature death. Critically, an exogenous enzyme may correct the cellular enzyme deficiency. Hematopoietic stem cell transplant (HSCT) has been used in the treatment of MPS for over 30 years.Areas covered: This paper focuses on the principle of HSCT in MPS and presents current evidence of HSCT in MPS. Factors affecting the transplant and disease outcome, as well as strategies to improve outcomes in MPS I are highlighted.Expert opinion: Transplant outcomes have hugely improved over recent decades so that most patients are expected to survive and be engrafted with donor-derived, enzyme-competent leucocytes following a transplant. The influence of an engraftment on the clinical course of the patient depends critically on the age at transplant and the enzyme dose delivered by the graft. Early therapy is best since transplant is better at preventing disease progression than reversing established disease. Some MPS are more transplant-responsive than others, and some organs respond better than others. The clinical outcome of these refractory organs and diseases may be improved beyond what is possible with wild-type donors by enhancing enzyme delivery using gene-modified, autologous cells.