We are pleased to advise that Dr Marzena Kurzawa-Akanbi has been awarded the Michael J Fox Foundation research grant. The project is very much related to her PhD work which was funded by The Lewy Body Society.
Marzena has provided an abstract of her proposal.
Marzena Kurzawa-Akanbi, PhD
Institute of Neuroscience, Newcastle University

Project Title: Investigation of lipid metabolism in GBA associated parkinsonism.

Co-investigators: Dr Christopher Morris, Newcastle University and Prof. Phil Whitfield, University of the Highlands and Islands.

I received my PhD in 2011 from Newcastle University. My PhD research was funded by the Lewy Body Society and the research project looked into complex aspects of biology of Dementia with Lewy bodies (DLB) and Parkinson’s disease (PD). The particular focus was on a potential link between the risk of developing DLB and PD and carrying genetic changes in the Glucocerebrosidase (GBA) gene. Results of my study have been published in a scientific journal: Kurzawa-Akanbi M, Hanson PS, Blain PG, Lett DJ, McKeith IG, Chinnery PF and Morris CM (2012) “Glucocerebrosidase mutations cause altered endoplasmic reticulum and lysosomal composition in Lewy body disease”, J Neurochem, 123 (2), pp. 298-309. My work has also played a very significant part in a large international collaborative study that has provided strong evidence that genetic changes in the GBA gene are linked to a higher risk of developing DLB and PD (Nalls MA, Duran R, Lopez G, Kurzawa-Akanbi M, McKeith IG, Chinnery PF, Morris CM et al. (2013) “A Multicenter Study of Glucocerebrosidase Mutations in Dementia with Lewy Bodies”, JAMA Neurol, 70 (6), pp. 727-35v).

We know that the changes in GBA in nerve cells may eventually cause an increase in abundance of alpha-synuclein, the protein that forms Lewy bodies, and kill the nerve cells. How the changes in GBA lead to Lewy bodies and nerve cell death is however unclear, but solving this scientific question will point towards new treatments for PD and DLB.

We think that the process of making lipids (fats) in nerve cells is changed by abnormalities in GBA, and these changes cause alpha-synuclein to clump and form Lewy bodies. Patients with DLB and PD with normal GBA may also have some changes in lipid levels.

This study will look at different aspects of DLB and PD biology to allow us to prove our idea.

1) We will measure the different types of lipids in brain tissue obtained after death from people with PD, DLB and normal brain donors who had genetic changes in GBA and compare the lipids to those from PD, DLB and healthy individuals with normal GBA.
2) Cells produce tiny particles called exosomes which allow material to pass from one cell to another. We will purify these exosomes from brain tissue and from cerebrospinal fluid (the fluid that bathes the brain) and test them for alpha-synuclein and lipids. This will tell us if alpha-synuclein forms clumps in exosomes and spreads within the brain, but also if lipid changes caused by abnormal GBA increase alpha-synuclein spread.

By identifying how changes in GBA actually cause clumping of alpha-synuclein, we should be able to design ways to stop this process. Lipid abnormalities in the brain, if identified, can be targeted through pharmacological interventions. Similarly, if exosomes promote clumping or spreading of alpha-synuclein, it means reducing exosome spreading will provide a basis for developing therapies for individuals at risk of developing PD or DLB.