Neurodegenerative metabolic diseases mainly affect children and often lack effective treatments. Some, such as the lysosomal storage disease, Mucopolysaccharidosis (MPS) I, can already be partly treated by allogeneic transplantation of bone marrow or cord blood derived stem cells from a healthy donor, but there is often a high associated risk of morbidity and mortality when using mismatched transplants.
Dr Bigger’s Stem Cell & Neurotherapies laboratory uses a multidisciplinary approach to investigate stem cell and gene therapies for neurological diseases. It consists of two programmes
MPS lysosomal disease group
- Comparative neuropathology and mechanisms of neurodegeneration in models of MPS disease
- Clinical development of novel stem cell and gene therapies in neurodegenerative lysosomal diseases
- Biomarker development
- The therapeutic use of haematopoietic stem cell transplantation in neurodegenerative disease
- The use of substrate reducing agents to ameliorate mucopolysaccharide diseases.
The Brain Tumour group
- Brain tumour stem cell biology and their interaction with Microglia in vivo
- Novel therapies for brain tumours using high throughput drug screening in cancer stem cell lines derived from primary gliomas
We are primarily a research laboratory but have close clinical links, with both the MPS and metabolic disease patients and neurosurgical patients.
Image: Lentiviral transduced eGFP positive GL-261 glioma tumour cells implanted orthotopically into the brains of C57BL/6 mice, demonstrating the infiltrative component of microglia in the brain tumour microenvironment. Green: eGFP expressing GL261 cells, Red: Iba-1 microglia/macrophages, Blue: DAPI nuclear stain
2014 - Videolinks
2013 - Videolinks - Rare Disease Report
2012 - Videolinks
Main Areas of Expertise
Lysosomal disease model characterisation and treatment
Stem cell biology and treatment of primary brain tumours
Haematopoetic stem cell gene therapy and tolerance induction
Haematopoietic cell migration and interactions within bone marrow and neurological niches
Clinical translation of gene and cell therapies
The laboratory is funded by a programme grant and subsidiary grants from the UK Society for Mucopolysaccharide (MPS) diseases to Dr Bigger
We gratefully acknowledge past and present funders including: The Norah Al Balla foundation, Great Ormond Street Research Chraity, Action Medical Research, Jonah's Just Begun, The Lady Shauna Gosling Trust, The Sanfilippo Children's Research Foundation (Canada), The Ollie G Ball,The National MPS Society (US), The Irish MPS society, The Children's Bone Marrow Trust, BBSRC, The Manchester Biomedical Research Centre, Department of Health, CMFT NHS trust endowments, The Association for Glycogen Storage Disorders, The Brain Tumour Charity, The GEM appeal, Lois Gosling,
as well as contributions from the MPS societies of Austria, Canada, Germany, Ireland, Japan, Netherlands, Spain, Sweden, Switzerland, UK and USA.