Metabolic Medicine
The department is heavily involved with clinical research, focusing on developing new therapies for children with rare metabolic disorders. Research studies have included observational studies as well as therapeutic clinical trials, ranging from early phase studies to Phase III clinical trials. The Willink Metabolic Unit currently has several clinical trials running for lysosomal storage disorders in conjunction with the Children’s Clinical Research Facility in the Royal Manchester Children’s Hospital.
The department has a strong track record in commercial clinical trials and has delivered several such studies conducted at the NIHR Wellcome Trust Children’s Clinical Research Facility. Many of these have been international, multi-centre clinical trials of enzyme replacement therapies for lysosomal storage disorders, and research undertaken in the department has contributed to the licensing of two such therapies within the last three years.
The research team have also conducted investigator-led clinical trials sponsored by Manchester University NHS Foundation Trust.
We work closely with other metabolic centres both within and outside the UK, the University of Manchester and other academic groups, and patient organisations such as the UK MPS Society.
Team Members
MCGM Clinical & Research
Name |
Role |
Dr Simon Jones |
Consultant in Paediatric Metabolic Disease |
Dr Alex Broomfield |
Consultant in Paediatric Metabolic Disease |
Dr Bernd Schwahn |
Consultant in Paediatric Metabolic Disease |
Dr Andrew Morris |
Consultant in Paediatric Metabolic Disease |
Dr Sergei Korenev |
Locum Consultant in Paediatric Metabolic Disease |
Dr Arunabha Ghosh |
Clinical Research Fellow |
Dr Aimee Donald |
Clinical Research Fellow |
Ms Laura Crowther |
Clinical Trials Manager |
The Willink Metabolic Unit
Key Collaborators
Name |
Role |
Dr Brian Bigger |
Stem Cell & Neurotherapies, University of Manchester |
Prof Rob Wynn |
Consultant Paediatric Haematologist, Bone Marrow Transplant Unit, Royal Manchester Children’s Hospital |
Dr Stewart Rust |
Consultant Clinical Psychologist, Willink Metabolic Unit |
Dr Catherine Breen |
Consultant Clinical Geneticist, Manchester Centre for Genomic Medicine |
Dr Siddharth Banka |
Consultant Clinical Geneticist, Manchester Centre for Genomic Medicine |
Prof William Newman |
Professor of Translational Genomic Medicine, Manchester Centre for Genomic Medicine |
Dr Stephen Hughes |
Consultant in Paediatric Immunology, Royal Manchester Children’s Hospital |
Mr Ian Kamaly-Asl |
Consultant in Paediatric Neurosurgery, Royal Manchester Children’s Hospital |
Mr Ian Bruce |
Consultant ENT Surgeon, Royal Manchester Children’s Hospital |
Miss Jane Ashworth |
Consultant Paediatric Ophthalmologist, Manchester Royal Eye Hospital |
Dr Indi Banerjee |
Consultant Paediatric Endocrinologist, Royal Manchester Children’s Hospital |
Dr Rachael Barber |
Consultant in Paediatric Intensive Care, Royal Manchester Children’s Hospital |
Dr Anu Goenka |
Clinical Research Fellow in Paediatric Immunology, Manchester Collaborative Centre for Inflammation Research, University of Manchester |
Research Projects
- VITAL (SurVival of Lysosomal Acid Lipase Deficiency (LAL-D) Infants Treated With SebelipAse aLfa): A multi-centre study evaluating the effect of sebelipase alfa on survival at 12 months of age in children with growth failure due to LAL-D. Sponsored by Alexion Pharmaceuticals. (Active, not recruiting)
- LAL-CL08: A Phase II, multi-centre study to evaluate the safety, tolerability, efficacy, and pharmacokinetics of sebelipase alfa in infants with rapidly progressive lysosomal acid lipase deficiency (LAL-D). Sponsored by Alexion Pharmaceuticals. (Active, not recruiting)
- GENiSIS2013: A Phase III randomised, double-blinded, placebo controlled trial of high dose oral genistein aglycone therapy in patients between 2 and 15 years old with MPS III A, B or C. Sponsored by Manchester University NHS Foundation Trust, funded by UK MPS Society. (Active, not recruiting)
- ASCEND: A phase I/II, multi-centre, open-label, ascending dose study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and exploratory efficacy of olipudase alfa in paediatric patients aged <18 years with acid sphingomyelinase deficiency. Sponsored by Sanofi-Genzyme. (Active, not recruiting)
- SHP-609-302: An open label extension of study HGT-HIT-094, evaluating long term safety and clinical outcomes of intrathecal idursulfase administered in conjunction with Elaprase® in patients with MPS II (Hunter Syndrome) and cognitive impairment. Sponsored by Shire Human Genetic Therapies Inc. (Active, not recruiting)
- ITIMHS (Immune Tolerance Induction with methotrexate in Hurler Syndrome): A single centre, open label study evaluating the efficacy of immune modulation with methotrexate in mitigating the antibody response to laronidase in children with severe MPS I (Hurler Syndrome). Sponsored by Manchester University Hospitals NHS Foundation Trust, funded by UK MPS Society. (Active, recruiting).
- Executive and social functioning in patients with Tyrosinaemia Type 1: An observational study exploring the executive, social-cognitive, and social functioning and behaviour of patients with Tyrosinaemia Type 1 from the age of 7 years. In collaboration with and sponsored by University Medical Center, Groningen. (Active, recruiting).
- ALXN1101-MCD-202: A Phase II/III, multi-centre, multinational, open-label study to evaluate the efficacy and safety of ALXN1101 in neonates with Molybdenum Cofactor Deficiency (MOCD) type A. Sponsored by Alexion Pharmaceuticals. (Active, recruiting).
- GMP2016: A pilot trial evaluating the tolerance, safety and acceptability of PKU GMPro, a whey protein derived feed for the dietary management of phenylketonuria in children and adults. In collaboration with Great Ormond street Hospital. Sponsored by Nutricia UK Ltd. (Active, recruiting).
- Gaucherite stratified medicine project: An observational study to develop predictive measures to stratify clinical outcomes in children and adults with Gaucher disease and responses to specific therapies. Funded by MRC, in collaboration with and sponsored by Cambridge University Hospitals NHS Foundation Trust. (Active, recruiting).
- Neurological Disease Severity Assessment Study: An observational study to evaluate the use of new technology as a way of monitoring disease severity in patients with neurological diseases, including the use of wearable technology over a long, continuous period of time as a way of monitoring ambulation and ataxia in paediatric diseases. Funded by the Gaucher Association, sponsored by the University of Manchester. (Active, recruiting).
- Morquio A Registry Study (MARS): A registry study to characterize and describe the MPS IVA population as a whole, including the variability between patients, progression of the disease over time and natural history of MPS IVA.
- Database Development for Newborn Screening Disorders: A study to develop a genotype-phenotype correlative database for six newborn screening disorders by performing Next Generation DNA Sequencing on a small panel of genes and collecting medical record information from screen positive and clinically affected patients.
Recent Publications
- Baruteau J, Jameson E, Morris AA, et al. Expanding the phenotype in argininosuccinic aciduria: need for new therapies. J Inherit Metab Dis 2017;40(3):357-68. doi: 10.1007/s10545-017-0022-x [published Online First: 2017/03/03]
- Ghosh A, Schlecht H, Heptinstall LE, et al. Diagnosing childhood-onset inborn errors of metabolism by next-generation sequencing. Archives of Disease in Childhood 2017 doi: 10.1136/archdischild-2017-312738
- Korenev S, Morris AA. When to Suspect and How to Diagnose Mitochondrial Disorders? Indian journal of pediatrics 2016;83(10):1157-63. doi: 10.1007/s12098-015-1932-y [published Online First: 2016/01/14]
- Lum SH, Stepien KM, Ghosh A, et al. Long term survival and cardiopulmonary outcome in children with Hurler syndrome after haematopoietic stem cell transplantation. Journal of Inherited Metabolic Disease 2017;40(3):455-60. doi: 10.1007/s10545-017-0034-6
- Ghosh A, Urquhart J, Daly S, et al. Phenotypic Heterogeneity in a Congenital Disorder of Glycosylation Caused by Mutations in STT3A. Journal of child neurology 2017;32(6):560-65. doi: 10.1177/0883073817696816
- Jones SA, Rojas-Caro S, Quinn AG, et al. Survival in infants treated with sebelipase Alfa for lysosomal acid lipase deficiency: an open-label, multicenter, dose-escalation study. Orphanet Journal of Rare Diseases 2017;12(1):25. doi: 10.1186/s13023-017-0587-3
- Javed A, Aslam T, Jones SA, et al. Objective Quantification of Changes in Corneal Clouding Over Time in Patients With Mucopolysaccharidosis. Investigative Ophthalmology & Visual Science 2017;58(2):954-58. doi: 10.1167/iovs.16-20647
- Laraway S, Mercer J, Jameson E, et al. Outcomes of Long-Term Treatment with Laronidase in Patients with Mucopolysaccharidosis Type I. The Journal of Pediatrics 2016;178:219-26.e1. doi: http://dx.doi.org/10.1016/j.jpeds.2016.08.033
- Breen C, Mercer J, Jones SA, et al. Maternal mosaicism for IDUA deletion clarifies recurrence risk in MPS I. Human genome variation 2016;3:16031. doi: 10.1038/hgv.2016.31 [published Online First: 2016/10/22]
- Ghosh A, Banerjee I, Morris AAM. Recognition, assessment and management of hypoglycaemia in childhood. Archives of Disease in Childhood 2016;101(6):575.
- Ghosh A, Miller W, Orchard PJ, et al. Enzyme replacement therapy prior to haematopoietic stem cell transplantation in Mucopolysaccharidosis Type I: 10 year combined experience of 2 centres. Molecular Genetics and Metabolism 2016;117(3):373-77. doi: https://doi.org/10.1016/j.ymgme.2016.01.011
- Jones SA, Breen C, Heap F, et al. A phase 1/2 study of intrathecal heparan-N-sulfatase in patients with mucopolysaccharidosis IIIA. Mol Genet Metab 2016;118(3):198-205. doi: 10.1016/j.ymgme.2016.05.006 [published Online First: 2016/05/24]
- Jones SA, Valayannopoulos V, Schneider E, et al. Rapid progression and mortality of lysosomal acid lipase deficiency presenting in infants. Genetics in medicine : official journal of the American College of Medical Genetics 2016;18(5):452-8. doi: 10.1038/gim.2015.108 [published Online First: 2015/08/28]
- Jameson E, Jones S, Remmington T. Enzyme replacement therapy with laronidase (Aldurazyme((R))) for treating mucopolysaccharidosis type I. The Cochrane database of systematic reviews 2016;4:Cd009354. doi: 10.1002/14651858.CD009354.pub4 [published Online First: 2016/04/02]
- Broomfield A, Jones SA, Hughes SM, et al. The impact of the immune system on the safety and efficiency of enzyme replacement therapy in lysosomal storage disorders. J Inherit Metab Dis 2016;39(4):499-512. doi: 10.1007/s10545-016-9917-1 [published Online First: 2016/02/18]
- Jones SA, Bialer M, Parini R, et al. Safety and clinical activity of elosulfase alfa in pediatric patients with Morquio A syndrome (mucopolysaccharidosis IVA) less than 5 y. Pediatr Res 2015;78(6):717-22. doi: 10.1038/pr.2015.169 [published Online First: 2015/09/04]
- Pal AR, Langereis EJ, Saif MA, et al. Sleep disordered breathing in mucopolysaccharidosis I: a multivariate analysis of patient, therapeutic and metabolic correlators modifying long term clinical outcome. Orphanet J Rare Dis 2015;10:42. doi: 10.1186/s13023-015-0255-4 [published Online First: 2015/04/19]
- Aldenhoven M, Wynn RF, Orchard PJ, et al. Long-term outcome of Hurler syndrome patients after hematopoietic cell transplantation: an international multicenter study. Blood 2015;125(13):2164-72. doi: 10.1182/blood-2014-11-608075 [published Online First: 2015/01/28]
- Langereis EJ, van Vlies N, Church HJ, et al. Biomarker responses correlate with antibody status in mucopolysaccharidosis type I patients on long-term enzyme replacement therapy. Mol Genet Metab 2015;114(2):129-37. doi: 10.1016/j.ymgme.2014.10.012 [published Online First: 2014/12/04]
- Schwahn BC, Van Spronsen FJ, Belaidi AA, et al. Efficacy and safety of cyclic pyranopterin monophosphate substitution in severe molybdenum cofactor deficiency type A: a prospective cohort study. Lancet 2015;386(10007):1955-63. doi: 10.1016/s0140-6736(15)00124-5 [published Online First: 2015/09/08]