Dr James Davison 

James Davison is a consultant in paediatric metabolic medicine at Great Ormond Street Hospital, London. His clinical practice encompasses all aspects of inherited metabolic disorders, with a focus on lysosomal storage disorders. He supports novel therapy implementation through roles on the Trust Drugs and Therapeutics Committee, as PI/CI on several interventional clinical trials, and has acted as clinical expert for NICE appraisal processes. James is engaged in endeavours to expand newborn screening for metabolic disorders. He is also passionate about education and training, and is a faculty member of the SSIEM Academy/ Education and Training Committee. James is currently chair of the BIMDG.

Are indications for haematopoietic stem cell transplant in IMD changing?

Haematopoietic stem cell transplant (HSCT) was first undertaken as a treatment for Hurler syndrome by John Hobbs in 1980. 45 years later, HSCT as a means of enzyme replacement via cross-correction mechanisms remains the standard of care treatment for mucopolysaccharidosis type 1 (Hurler phenotype) and for other lysosomal disorders including alpha mannosidosis and forms of osteopetrosis. HSCT is also considered in some situations as a therapy for other mucopolysaccharidoses where central nervous system treatment is warranted including MPS II (Hunter) and MPS VII (Sly) syndromes.  The role of HSCT in other storage disorders including metachromatic and globoid cell (Krabbe) leukodystrophies, and fucosidosis is less established but remains a clinical option. HSCT is also a proven therapy for early cerebral involvement in the peroxisomal disorder X-linked adrenoleukodystrophy (X-ALD), albeit by a different mechanism of action than for the lysosomal enzyme defects. Recently, availability of HSCT has been expanded to adult males with cerebral X-ALD. The utility of HSCT in preventing or addressing other phenotypic aspects of X-ALD including progressive adrenomyeloneuropathy remains unclear.Thymidine phosphorylase (TP) deficiency leads to secondary abnormalities of mitochondrial DNA (mtDNA)  by disturbing the systemic pool of pyrimidine nucleotides, and thus causes Mitochondrial NeuroGastroIntestinal Encephalomyopathy (MNGIE). HSCT as a means of providing a source of functioning TP can normalise pyrimidine nucleotide pools, address mtDNA defects, and lead to clinical benefit, although with a high morbidity/mortality risk and alternative approaches including liver transplant may be considered.Other recent novel applications of HSCT for metabolic disorders including for triose phosphate isomerase deficiency will also be considered.While HSCT is an important therapy and is standard of care for an expanding range of metabolic disorders, the limitations of this therapeutic approach are clear and novel approaches to improving efficacy, including through ex vivo gene therapy stem cell transplants, are required.