My work focuses on lysosomal dysfunction and glycosphingolipid dysregulation in rare and common neurodegenerative diseases.
Historically, the early-onset rare neurodegenerative lysosomal storage disorders (LSDs) have been studied as discrete metabolic diseases in their own right. However, in recent years some unanticipated and exciting links with common late-onset neurodegenerative diseases, like Parkinson’s disease (PD) and amyotrophic lateral sclerosis (ALS), have emerged.
Recent reports show changes in glycosphingolipid (GSL) levels in these more common neurodegenerative disorders. However, the relationship between basic biochemical mechanisms like lysosomal dysfunction and lipid dysregulation in ALS and PD remains poorly understood.
In this project, I am now investigating the basic biological processes causing GSL changes and lysosomal dysfunction in these diseases.
- Lysosomal dysfunction in PD and ALS
- Glycosphingolipid dysregulation in PD and ALS
- Evaluation of the effects of lipid-targeted therapies in rare and more common diseases
- Identification of novel lipid-related biomarkers before onset of disease
This work is supported by Parkinson’s disease UK and Spedding Research Solutions SARL, France.
Glycosphingolipid levels and glucocerebrosidase activity are altered in normal aging of the mouse brain.
Hallett PJ. et al, (2018), Neurobiol Aging, 67, 189 - 200
AAV9 intracerebroventricular gene therapy improves lifespan, locomotor function and pathology in a mouse model of Niemann-Pick type C1 disease.
Hughes MP. et al, (2018), Hum Mol Genet
Altered Expression of Ganglioside Metabolizing Enzymes Results in GM3 Ganglioside Accumulation in Cerebellar Cells of a Mouse Model of Juvenile Neuronal Ceroid Lipofuscinosis.
Somogyi A. et al, (2018), Int J Mol Sci, 19
N-Butyl-l-deoxynojirimycin (l-NBDNJ): Synthesis of an Allosteric Enhancer of α-Glucosidase Activity for the Treatment of Pompe Disease.
D'Alonzo D. et al, (2017), J Med Chem, 60, 9462 - 9469
Development of gene therapy for Niemann-Pick Type C disease
Hughes M. et al, (2017), HUMAN GENE THERAPY, 28, A15 - A15