UCL Great Ormond Street Institute of Child Health


Great Ormond Street Institute of Child Health


Dr Philippa Mills

The aim of the research of my group is to discover the origins of disease for children with inherited metabolic disorders. We use our knowledge of the metabolic biochemical pathways in parallel with next generation sequencing methodologies to facilitate identification of candidate genes in patients, mutations in which are then investigated further in model systems. Greater understanding of metabolic disorders will enable identification of more effective treatments for these life-threatening diseases. We are particularly interested in those disorders that cause neurological disease especially the vitamin B6-dependent epilepsies and disorders of hypermanganesemia which result in a Parkinsonian-like movement disorder. 

Research Areas: 

  1. Paediatric Metabolic Disorders

Funding: Great Ormond Street Hospital Children's Charity Leadership Award (Principal Investigator)

40% of patients with suspected metabolic disorders are undiagnosed; we are using state-of-the-art methods for DNA and metabolite analysis to diagnose and characterise novel disorders.  We aim to understand the role of genes involved in these disorders in order to identify better treatments. Once diagnosed rapid tests are required so that patients with similar clinical symptoms can be screened and treated appropriately and that treatment can be monitored; we are developing tests that need only a drop of blood.  We are particularly interested in those disorders that cause neurological disease especially the vitamin B6-dependent epilepsies.

  1. Alpha-1 antitrypsin to improve the efficacy of hepatocyte transplantation in children with liver-based metabolic disease

Funding: MRC DPfS grant. Principal Investigator at ICH – Collaborative grant with co-investigators at Kings College: Prof. Anil Dhawan (PI), Dr Emer Fitzpatrick, Dr Celine Filippi, Dr Ragai Ramsis Mitry, Dr Abdel Douiri, Dr Clare Flach

We are developing mass-spectrometry based assays to ascertain efficacy of hepatocyte transfer in humans and to investigate the mechanisms of how alpha-1 antitrypsin modifies the innate immune response following hepatocyte transplantation by studying the serum cytokine response and the phenotype of circulating inflammatory cells.

  1. Optimisation and bioperformance of a novel formulation of pyridoxal-5-phosphate for treatment of pyridox(am)ine 5’-phosphate oxidase deficiency induced epilepsy in children

Funding: Great Ormond Street Children’s Charity (co-investigators: Prof. Catherine Tuleu (PI), Dr. Emma Footitt, Prof. Peter Clayton, Dr. Ahad Rahim, Prof. Simon Heales)

Currently pyridoxal phosphate, which is used to treat children with PNPO-deficiency, is only available as a nutritional supplement in tablet or capsule forms. Unlike pharmacy only medicines these products are not regulated and can be problematic for clinical use. Our preliminary data has shown that there is a high risk of inaccurate dosing with these products that are also not stable when mixed in water for administration, forming compounds that are possibly toxic to the liver. We are therefore investigating new formulations that may be more suitable for administration.

  1. Health and the understanding of metabolism, aging and nutrition (HUMAN)

Funding; European Union SME Targetive collaborative project (Co-investigators: Dr. Kevin Mills (PI), Prof. Peter Clayton, Prof. Paul Gissen, Dr. Philippa Mills, Wendy Heywood)