4.3.2. Metabolic diseases

Principles of stem cell biology and cancer: future applications and therapeutics. Edited by T. Regad, T. J. Sayers and R. C. Rees. John Wiley & Sons (2015)

Part I. Stem Cells


HSC therapy can also be used to treat certain inherited metabolic disorders caused by single gene mutations. Untreated, these can be devastating. As an example, in Hurler syndrome (lack of the lysosomal enzyme alphaL-iduronidase (Boelens et al., 2009)), patients are unable to break down glycosaminoglycans. This results in a progressive disease that is fatal in early childhood, with symptoms including psychomotor retardation, skeletal abnormalities and life-threatening cardiac and pulmonary problems. Available treatment options are limited. Cells can take up externally provided enzyme, but enzyme replacement therapy is limited by cost and, even more importantly, by the inability of the enzyme to cross the blood – brain barrier, making it impossible to treat symptoms that involve the central nervous system (CNS). The only treatment option currently available for diseases that involve the CNS is bone marrow or cord blood transplantation. The engrafting haematopoietic cells that produce the missing enzyme are present throughout the body, including – in the form of macrophages and microglial cells – the CNS (Prasad and Kurtzberg, 2010a, 2010b; Valayannopoulos and Wijburg, 2011).

Over 2000 patients with various inherited metabolic disorders have been treated this way in the past 30 years. UCB has become the preferred source, because patients have to be treated as early as possible, and UCB is available from tissue banks, engrafts better and results in higher enzyme levels. Improvement – especially developmental – can be quite dramatic. Where necessary, supplemental treatment with enzyme replacement therapy can be initiated at any time post-transplant (Valayannopoulos et al., 2010). The associated musculoskeletal defects, however, have proven unresponsive to this mode of treatment, and require other (surgical) intervention.

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