Dr Bridget Bax’s research focuses on rare inherited diseases, in particular identifying the molecular mechanisms that contribute to disease pathology and the development of novel therapies for translation into the clinical setting.
The work of Dr Bax and her team focuses on improving the understanding of the pathogenic mechanisms of rare inherited diseases and developing cell-based therapies for the treatment of diseases with unmet needs.
A major area of interest is the application of proteomic and genomic technologies in the identification and validation of biomarkers in body fluids (urine and blood) in patients with the rare and fatal disease mitochondrial neurogastrointestinal encephalomyopathy (MNGIE). The goals of this work are three-fold: to understand the pathophysiological mechanisms and metabolic derangements observed in patients with MNGIE, to provide a means of monitoring more effectively clinical and biochemical response to therapy, and to enable the tracking of disease progression in diagnosed patients.
The second aspect of the team’s research is the development of cell-based therapies for the treatment of inherited diseases, and in particular the use of the autologous erythrocyte as a vehicle for delivering enzyme replacement therapies and other therapeutic proteins. The encapsulation technology has the advantage of prolonging the circulatory half-life of proteins, minimizing immunogenic reactions and negating the need for expensive chemical modification. The team have employed this therapeutic approach in the clinical setting for over 18 years in the treatment of an adult patient with adenosine deaminase deficiency.
More recently this platform technology was applied in the form of erythrocyte encapsulated thymidine phosphorylase (EE-TP) to the compassionate treatment of patients with MNGIE. Orphan Drug Designation was granted for EE-TP by both the Food and Drug Administration (USA) and European Medicines Agency, and a European clinical trial of EE-TP (funded by the MRC) is due to commence in 2016. The technology was exclusively licensed to Orphan Technologies by St. George’s University of London in 2012 and a patent for the treatment of MNGIE was filed in 2012.
Dr Bax graduated with a BSc (Hons) in Biochemistry from Royal Holloway, University of London before joining the Institute of Obstetrics and Gynaecology, University of London as a Research Biochemist. She then joined the Royal Postgraduate Medical School, University of London as a research assistant and was subsequently awarded her PhD in 1992. After a postdoctoral position at St George's, University of London, she was appointed Senior Research Fellow in 2002 when she started as an independent researcher in the area of rare inherited metabolic diseases.
She was appointed as a Reader in Rare Diseases in 2013. Bridget also serves as a visiting professor in the Faculty of Life Sciences and Computing at London Metropolitan University, London.
Dr Bax is a member of the Biochemical Society, Institute of Biology (Chartered Biologist), the Society for the Study of Inborn Errors of Metabolism and the International Society for Extracellular Vesicles.
She is a Scientific Advisor to EryTech Pharma, Chair of Orphan Technologies Scientific Advisory Board, and a member of the Rare Renal Disease Group.
Dr Bax contributes to the non-academic, patient-based community in her role as Honorary Secretary to PUMPA, a registered charity that aims to advance education about purine and pyrimidine metabolic disorders to professionals and the public.
Michelle Levene (PhD student). Project: Characterisation of biomarkers for monitoring disease progression and treatment efficacy in mitochondrial neurogastrointestinal encephalomyopathy.
Dario Pacitti (PhD student). Project: The development of knock-out cell culture models for investigating the underlying molecular mechanisms that contribute to the neuronal aspects of Mitochondrial Neurogastrointestinal Encephalomyopathy (MNGIE).
Dr Murray Bain. Team clinician.
Dr Niranjanan Nirmalananthan. Team Consultant Neurologist
Chapman, T.P., Hadley, G., Fratter, C., Cullen, S., Bax, B.E., Bain, M.D., Sapsford, A., Poulton J., and Travis, S.P.L. (2014) Unexplained gastrointestinal symptoms: Think mitochondrial myopathy. Digestive and Liver Disease. 46, 1-8.
Bax, B.E., Bain, M.D., Scarpelli, M., Filosto, M., Tonin P., and Moran, N. F. (2013) Clinical and biochemical improvements in a patient with MNGIE following enzyme replacement. Neurology. 8, 1269-1271.
Talaulikar, V., Kronenberger , K., Bax , B.E., Moss, R. and Manyonda, I. (2014) Differences in collagen ultrastructure of human first trimester decidua basalis and parietalis: implications for trophoblastic invasion of the placental bed. Journal of Obstetrics and Gynaecology Research. 40, 80-88.
Levene, M., Coleman, D., Kilpatrick, H., Fairbanks, L., Gangadharan, B., Gasson, C., and Bax, B.E. (2013) Preclinical toxicity evaluation of erythrocyte-encapsulated thymidine phosphorylase in BALB/c mice and Beagle dogs: an enzyme replacement therapy for mitochondrial neurogastrointestinal encephalomyopathy. Toxicological Sciences. 131:311–324.
Gasson C., Levene, M. and Bax, B.E. (2013) The development and validation of an immunoassay for the measurement of anti- thymidine phosphorylase antibodies in mouse and dog sera. Journal of Pharmaceutical and Biomedical Analysis. 72:16-24.
Fairbanks, L.D., Levene, M., and Bax, B.E. (2013) Validation of a HPLC method for the measurement of erythrocyte encapsulated thymidine phosphorylase (EE-TP) activity. Journal of Pharmaceutical and Biomedical Analysis 76: 8– 12.
Poor outcome in a MNGIE Patient with a novel TYMP mutation: the need for early diagnosis. (2012) Scarpelli, M., Russignan, A., Zombor, M., Bereczki, C., Zappini, F., Buono, R., Bax, B.E., Padovani, A., Tonin P., and Filosto, M. Case Reports in Neurology 4:248–253.
Levene, M., Bain, M.D, Fairbanks, L.D., Moran, N.F. and Bax, B.E (2012). Erythrocyte encapsulated thymidine phosphosphorylase (EE-TP) for the treatment of mitochondrial neurogastrointestinal encephalomyopathy (MNGIE). Journal of Inherited Metabolic Disease 35:S150-S150.
Talaulikar, V., Bax, B.E., Page, N., and Manyonda, I. (2012) A novel hysteroscopic technique for accurate biopsy of the decidua basalis and parietalis: implications for progress in research on the early events of human placentation. Placenta. 33: 473-479.
Godfrin, Y. and Bax, B.E. (2012) Enzyme bioreactors as drugs. Drugs of the Future. 37: 263-272.
Godfrin, Y., Horand, F., Franco, R., Dufour, E., Kosenko, E., Bax, B.E., Banz, A., Skorokhod, O.A., Lanao, J.M., Vitvitsky, V., Sinauridze, E., Bourgeaux, V., and Gunter, K.C. (2012). Meeting highlights: international seminar on the red blood cells as vehicles for drugs. Expert Opinion on Biological Therapy. 12: 127- 133.
Broberg, C.S., Jayaweera, A.R.,Diller, G.P., Prasad, S.K., Thein, S.L., Bax, B.E., Burman, J., Gatzoulis, M.A. (2011) Seeking the Optimal Relation between Oxygen Saturation and Hemoglobin Concentration in Adults with Cyanosis from Congenital Heart Disease. American Journal of Cardiology. 107: 595-599.
Moran, N.F., Bain, M.D., and Bax, B.E. (2010) MNGIE without elevated thymidine Levels. Archives of Neurology. 67: 644-645. Gutiérrez Millán, C., Bax, B.E., Zarzuelo Castañeda, A., Sayalero Marinero, M.L. and Lanao, J.M. (2008) In vitro studies of amikacin-loaded human carrier erythrocytes. Translational Research. 152: 59-66.
Moran, N.F., Bain, M.D., Muqit, M. and Bax, B.E. (2008) Carrier erythrocyte entrapped thymidine phosphorylase therapy in MNGIE. Neurology. 71: 686-688.
Bax, B.E., Bain, M.D., Fairbanks, L.D., Webster, A.D.B., Ind, P.W., Hershfield, M.S. and Chalmers, R.A. (2007) A nine year evaluation of carrier erythrocyte encapsulated adenosine deaminase therapy in a patient with adult-type adenosine deaminase deficiency. European Journal of Haematology, 79: 338-348.
Broberg, C.S., Ujita, M., Prasad, S., Li, W., Rubens, M., Bax, B.E., Davidson, S.J., Bouzas, B., Gibbs, J.S.R., Burman, J. and Gatzoulis, M.A. (2007) Pulmonary Arterial Thrombosis in Eisenmenger Syndrome is Associated with Biventricular Dysfunction and Decreased Pulmonary Flow Velocity. Journal of the American College of Cardiology, 50: 634-642.
Bax, C., Baggott, G., Howey, E., Pellet-Many, C., Rayne, R., Neonakia, M., Bax, B.E. and Branford White, C. (2006) Evaluation of Formative Computer-based Assessment by Cell Biology Students with Differing Entry Qualifications and Ethnicity. Bioscience Education e-Journal. 8: 8-5.
Murray A.M., Pearson, I.F.S., Chalmers R.A., Bain , M.D. and Bax , B.E . (2006) The mouse immune response to carrier erythrocyte entrapped antigens. Vaccine 24, 6129-6139.
Broberg, C.S., Bax, B.E., Rampling, M.W., Okonko, D.O., Bayne, S., Harries, C., Davidson, S.J., Uebing, A., Khan, A.A., Thein, S., Gibbs, J.S.R., Burman, J. and Gatzoulis, M.A. (2006) Blood Viscosity and its Relation to Iron Deficiency, Symptoms, and Exercise Capacity in Adults with Cyanotic Congenital Heart Disease. Journal of the American College of Cardiology, 48, 356-365.
Bax, B.E., Richfield, L., Bain, M.D., Mehta, A.B., Chalmers, R.A. and Rampling, M.W. (2005) Haemorheology in Gaucher disease. European Journal of Haematology 75, 252–258.
Food and Drug Administration (2010). Recombinant thymidine phosphorylase for the treatment of mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) due to thymidine phosphorylase deficiency. Reference 10-3248
European Medicines Agency (2011). Recombinant thymidine phosphorylase encapsulated in autologous erythrocytes for the treatment of mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) due to thymidine phosphorylase deficiency.Reference EU/3/11/856
Treatment for mitrochondrial neurogastrointestinal Encephalomyopathy (MNGIE). New European Patent Application No. 12756551.3 National Phase of PCT/GB2012/052157 B.E Bax & M.D. Bain
Orphan Technologies, Switzerland
Dr Nicholas Moran, Department of Neurology, Kings College Hospital, London
Dr Atul Mehta, Lysosomal Storage Disorder Unit, Royal Free and University College Medical School, London
Professor José Lanao, Faculty of Pharmacy University of Salamanca, Spain
Dr Lynette Fairbanks, Purine Research Laboratories, St Thomas' Hospital London
Dr Mauro Scarpelli, Insitute of Neurology, University of Verona, Italy
Dr Massimiliano Filosto, University Hospital "Spedali Civili", Brescia, Italy
Dr Paola Tonin, Insitute of Neurology, University of Verona, Italy
Professor Hanna Mandel, Rambam Health Care Campus,
Israel Peter Mollison, St. George’s Trust
Eric Che, St. George’s Trust
Central South Coast Specialist Services Confederation
Biotechnology and Biological Sciences Research Council (BBSRC)
Purine Metabolic Patients’ Association
United Mitochondrial Disease Foundation (UMDF)
Medical Research Council (MRC)
Higher Education Funding Council for Britain