What Ferblanc supported in 2019
Dr Leonidas Chouliaras (University of Cambridge)
In 2019, Ferblanc was delighted to provide a grant of £10,000 to Dr Leonidas Chouliaras, Clinical Lecturer in Old Age Psychiatry at the University of Cambridge towards his research “A Pilot Study on neuron specific methylomic profiling in Dementia with Lewy Bodies”. The study is due to run until July 2022, and we will post further updates on its progress in due course.
Leo summarises the project scope as follows:
“This study focuses on Dementia with Lewy Bodies (DLB), a common yet unstudied dementia. DLB patients get the memory symptoms of Alzheimer’s disease and symptoms of Parkinson’s disease such as tremor and stiffness. DLB is named after Lewy Bodies, the abnormal deposits of a protein called a-synuclein which accumulate in the brain cells of affected individuals. This makes brain cells lose their function and cause dementia. Currently, there is no cure for DLB and better understanding of what happens in the brains of patients will help us find new treatments. This project will study epigenetics in donated brains of patients with DLB and individuals without dementia. Epigenetics are the switches that turn on and off genes that produce proteins. This work will focus on the epigenetic tag of DNA methylation, which indicates whether a gene is “on” or “off”. By using advanced technologies, we will identify if any methylation tags are altered in DLB. We will also test whether the brain cells that are most affected by DLB have different methylation tags compared to neighbouring healthier cells. This work will help to better understand the condition and direct efforts for identifying new medicines.”
In March 2021, Dr Chouliaras provided the following update:
“Over the last year of the award I have been progressing with my objectives. Unfortunately, due to the Covid-19 pandemic which led to redeployment and increased workload and delays arising from revised laboratory procedures the pace of the progress has not been as initially planned. These affect the access, availability and use of the required facilities, such as the lab areas to process samples, use of the laser-capture microdissection microscope and access to the DNA sequencing facilities. Despite the adversities, so far I have received all required human brain sections from patients with Lewy Body Dementia and controls from the Cambridge and Newcastle Brain bank and have carried out the immunohistochemistry experiments to label the neurons with α-synuclein. Over the last few months I have been focusing on the final objectives of the project which are to collect cells using laser-capture microdissection and isolate DNA for sequencing. Some of the samples I have processed are now at the sequencing facility for DNA methylation sequencing and I await the final data for analysis and publication of findings. Overall the work is still ongoing and I am in the process of data collection and processing which continues in the coming months”
In April 2022, Dr Chouliaras provided the following update:
“Over the last 12 months I have been progressing with my objectives. Due to the Covid-19 pandemic and the impact it had on experimental research, the progress is unfortunately slower than initially planned. There is a higher load of administrative burden for all aspects of the work, deliveries of required reagents are significantly delayed and lab facilities are not as available as prior to the pandemic and require prior booking due to capacity restrictions and the implementation of new risk assessments. My work was previously delayed due to my clinical redeployment and the lockdown. Later on one of the lab facilities required was closed for refurbishment for several months and I was not able to access the highly specialist equipment required for the project (laser-capture microdissection microscope) while there were delays with processing samples at the DNA next generation core-sequencing facility that operated at limited capacity due to the pandemic. These issues are now being resolved and over the last 6 months I have been able to access and use the laser-microdissection microscope and have essentially completed most experimental aspects of the project with only the final step of DNA methylation sequencing remaining to be completed. This step is carried out by highly specialised collaborating staff the University’s DNA sequencing core facility. From our experience so far it appeared that the initial plan for reduced representation bisulphite sequencing method of DNA methylation sequencing is not as reliable with low inputs of DNA starting material and we have now optimised an alternative method of whole genome bisulphite sequencing for generating DNA methylation data that is tailored for use with low input DNA material. Due to the reduction of DNA sequencing costs since the start of the grant this slight amendment in the experimental protocol is not expected to affect costs and will essentially yield higher quality and more in-depth data. The work is now well undergoing and expect all aspects of experimental work to be completed in the coming 6 months.’
In April 2023, Dr Chouliaras provided the following final update:
Over the last 12 months I have completed this project. Following the initial delays associated with the Covid-19 pandemic, through support from Ferblanc I have been able to study the role of the epigenetic mechanism of DNA methylation in Lewy Body Dementia. In particular I have obtained frozen autopsy brain tissues from patients with Lewy Body dementia and matched control donors and using a laser microdissection microscope method have been able to isolate neurons with Lewy Bodies and neurons without the pathology from cases and controls. Through collaborative work have isolated DNA from these neurons and carried out genome wide DNA methylation bisulphite sequencing to identify genes that are differentially methylated between Lewy Body dementia cases and controls and also studied how the epigenetic programming of neurons with Lewy body pathology differs from that of neurons without the presence of pathology.
I am now in the process of the bioinformatics analysis of the DNA methylation sequencing data to be able to identify which specific genes are altered and plan to submit the data for publication at a high impact peer-reviewed scientific journal. My hope is that this work will contribute to a better understanding of pathophysiological mechanisms of Lewy body disorders and why some neurons in the brain are more vulnerable to pathology than others. I will use this data to apply for larger scale projects and continue to work towards leveraging epigenetic mechanisms for better understanding of disease and for identifying new gene targets for therapeutic development.
More information about the work undertaken in the Old Age Psychiatry Department can be found here: http://www.psychiatry.cam.ac.uk/oap/
ICM Paris - Project Attack-AVC
The research project Attack-AVC aims at understanding and identifying the neuromarkers of the brain recovery after a stroke in order to predict the capacity of motor/cognitive recovery of the patients and to adjust the care provided to them.
Ferblanc made a grant of €50,000 Euros to support this project which started in 2019. The project leaders, Dr Charlotte Rosso and Fabrizio De Vico Fallani, filed an authorization request to the French Agency for the Safety of Health Products and to the French Research Ethics Board which granted it. Meanwhile, a data scientist and a clinical monitor have been hired in order to run the research. Its protocol was finalized and the first patients have been included in the study.
The next phases of the project will be dedicated to:
- The definition of the cerebral profile of each patient included in the study ;
- The development of a predictive algorithm;
- The deployment of this technology for the patients with strokes.
An update has been provided in March 2021 and can be read here:
An update has been provided in April 2022 and can be read here:
More details about Project Attack-AVC can be found here (in French, but with the option to translate most of the wording).