Understanding how meningeal immune dysregulation promotes neurodegeneration in Lysosomal Storage Disorders

Lysosomal storage disorders (LSDs) are a group of rare genetic diseases affecting children, for whom there are almost no treatment options. Genetic mutations cause problems in the lysosomes of cells, leading to neurological problems, cognitive decline and ultimately death.
Some of these processes are similar to those found in Alzheimer’s Disease (AD) and children are often referred to as having paediatric AD. Therefore, understanding the processes in these diseases will have broad implications for neurodegenerative research.
This project aims to address if the immune system may play a fundamental role in exacerbating neurodegeneration in LSDs. A major advance of the past decade is the understanding that immune system plays a fundamental role in brain function in health and disease. At the cutting-edge of this research is understanding how the brain's borders, which are hubs of immune activity, drive brain disease.
The specific aims of this research are to:
1) Experimentally target the brain's borders, called the meninges, to improve brain function in a model of LSDs.
2) Test whether novel anti-inflammatory molecules can protect from ongoing brain damage in models of LSDs.
3) Investigate biomarkers of CNS disease progression and treatment efficacy in a rare cohort of patients participating in an open label Phase I-II clinical trial.
The potential applications and benefits are both specific and broad. This research programme has the potential to reveal new targetable pathways, understand underlying neurodegenerative mechanisms (not limited to LSDs), provide novel biomarkers to assess treatment efficacy and, crucially, enable experimental treatments in patients either in future or current clinical trials.