Brian Bigger

Brian Bigger is Professor of Advanced Therapeutics at the Institute for Regeneration and Repair, University of Edinburgh. Brian set up his independent research group at the University of Manchester in 2006 to understand the pathology of and develop treatments for neurological lysosomal storage disorders, a group of devastating childhood dementias. Here, the team defined roles for lysosomal storage and neuroinflammation in the pathology of neurological lysosomal diseases and developed several gene and cell therapy treatments for lysosomal diseases, three of which have now progressed to clinical trial. Brian was a co-founder of Orchard Therapeutics and past Chairman of the European Study Group for Lysosomal Diseases.  In 2023, Brian moved to the University of Edinburgh where his research group continues to focus on developing innovative gene and cell therapies for neurological diseases, including childhood dementias, and bringing these treatments to patients.

Galea Prize Lecture: Advances in new treatments for genetic brain diseases

Sanfilippo disease or mucopolysaccharidosis III (MPSIII) describes four clinically very similar lysosomal diseases (LSDs) caused by genetic defects in four unique lysosomal hydrolases that catabolise heparan sulphate. Affected children often present with developmental delay and recurrent ENT infections, typically displaying hyperactivity, behavioural and sleep issues and progressive loss of cognitive and later motor milestones with death typically in late teens in severe forms.

In this talk, I will discuss the rationale for using haematopoietic stem cell (HSC) gene therapy for neuropathic lysosomal storage diseases. The approach relies on genetically modifying blood stem cells to overexpress enzyme, typically using lentiviral vectors. Monocytes traffic to and engraft in the brain, delivering increased doses beyond the blood brain barrier. I will describe the state of the art for HSC gene therapy including work from our own lab on HSC gene therapy for Sanfilippo, exploiting some of the potential avenues for HSC gene therapy treatment likely to be tested in the clinic over the next few years.