Sialic acids as biomarkers for cardiovascular disease
Lead Research Organisation:
University of Reading
Department Name: Pharmacy
Abstract
Cardiovascular disease (CVD) is a major cause of morbidity and mortality, particularly in the West. Therefore there is a continued need for the identification of risk factors and disease markers, in order to allow early intervention, and better clinical outcomes, as well as develop methods for primary prevention. In some cases, the incidence of CVD in patients varies in a way that cannot be explained using recognized risk factors and markers, again highlighting the need for the identification of new biomarkers. Many large biomolecules in the body contain a particular carbohydrate called sialic acid (SA). This can exist in different forms. Previous studies have shown that SA levels are high in patients at risk of CVD. However, studies have not analytically detailed the different forms of SA in such patients in any depth. Increasing our understanding of the different SAs in blood and saliva samples from healthy subjects, as well as those at risk of CVD, and correlating those analytical observations with CVD risk and diet, is the main aim of this three year project.
During this industrial CASE award, different derivatives of SAs will be prepared at the University of Reading, using innovative chemical and enzymatic methods. The derivatives will then be included within well developed analytical protocols at the laboratories of Ludger Ltd that include chromatography and mass spectrometry. Patient focused studies will be undertaken at the University of Reading to obtain saliva and blood samples from both healthy volunteers and those who are at risk of CVD. The samples will be analysed at the laboratories of Ludger Ltd to determine biomarker features of the different forms of SA that are present. These levels will be compared with other CVD risk factors and the volunteer's diet, to see whether there are any correlations, using statistical methods.
Training will be provided throughout the programme in synthetic and analytical chemistry, and in carbohydrate profiling, within a Medicinal Chemistry context. As part of the programme the student will undertake placements at the laboratories of Ludger Ltd, at the Culham Science Centre in Abingdon. In addition to enhancing the progress of your PhD programme, the placements will also be used to show you how to undertake your work to a level that is recognised as good practice by the Federal Drug Administration (FDA) and the European Medicines Agency (EMA).
During this industrial CASE award, different derivatives of SAs will be prepared at the University of Reading, using innovative chemical and enzymatic methods. The derivatives will then be included within well developed analytical protocols at the laboratories of Ludger Ltd that include chromatography and mass spectrometry. Patient focused studies will be undertaken at the University of Reading to obtain saliva and blood samples from both healthy volunteers and those who are at risk of CVD. The samples will be analysed at the laboratories of Ludger Ltd to determine biomarker features of the different forms of SA that are present. These levels will be compared with other CVD risk factors and the volunteer's diet, to see whether there are any correlations, using statistical methods.
Training will be provided throughout the programme in synthetic and analytical chemistry, and in carbohydrate profiling, within a Medicinal Chemistry context. As part of the programme the student will undertake placements at the laboratories of Ludger Ltd, at the Culham Science Centre in Abingdon. In addition to enhancing the progress of your PhD programme, the placements will also be used to show you how to undertake your work to a level that is recognised as good practice by the Federal Drug Administration (FDA) and the European Medicines Agency (EMA).
People |
ORCID iD |
Helen Osborn (Primary Supervisor) | |
Jack Cheeseman (Student) |
Description | Ludger Ltd. |
Organisation | Ludger Ltd |
Country | United Kingdom |
Sector | Private |
PI Contribution | Visits to Ludger Ltd. at Culham Science Centre where I undertook method development projects to develop methods for the qauntitative analysis of sialic acid and its derivatives in human samples. Samples collected in house at Ludger were used for this development as well as urine samples obtained from previous research at Reading. For plasma, serum and saliva previous SOPs from Ludger were utilised and applied to the samples. Comparisons were made between the method carried out manually and carried out via robot. The robot was found to be more accurate. For urine samples, the quanities needed had to be adjusted due to concentration issues, as such different amounts were tested to determine the correct amounts of the sample to use for a good analysis. |
Collaborator Contribution | Ludger employees trained me in the procedures required as well as on the machines needed (HPLC and pipetting robot). I was also aided in carrying out these methods as I was not familiar with them nor the method employed and required training. |
Impact | Methods for analysis of sialic acids from human samples developed and improved upon. |
Start Year | 2017 |
Description | Marco Monopoli |
Organisation | Royal College of Surgeons in Ireland |
Country | Ireland |
Sector | Academic/University |
PI Contribution | Collaborated to purchase plasma samples from volunteers who have advanced cardiovascular diseases from BioIVT Biobank. Future collaboration to analyse samples collected from trial volunteers at Reading. Samples will be analysed for fibrinogen content to determine whether it is a good biomarker for cardiovascular disease and if the method for analysis is successful. This can be used to compare with our potential marker of sialic acid. |
Collaborator Contribution | Purchase of Biobank samples. Future training on analysis methods for fibrinogen analysis. Potential visit to Dublin for training and data collection. |
Impact | Purchase of Biobank samples for analysis of fibrinogen and sialic acids. |
Start Year | 2018 |
Title | Sialic acid as a biomarker |
Description | The aim is to investigate the use of sialic acid as a biomarker for cardiovascular disease. The investigation will determine the efficacy of the biomarker by comparing quantities of sialic acid and its acetylated derivatives in human samples (plasma, serum, urine and saliva) in healthy controls and volunteers with cardiovascular disease risk. This study aimed to recruit around 80 volunteers for the study, split equally between healthy and at risk of CVD. As well as split between male/female and by age groups. In total, 82 volunteers were recruited for the study, with a roughly even split between health and at risk and by gender. Each volunteer provided information for calculation of their QRISK score and four samples. These samples are then planned to be taken forward for quantitiative analysis of sialic acid derivatives. These sialic acid levels can subsequently be compared to QRISK scores to determine if there is a correlation between relative risk of cardiovascular mortality and cardiovascular risk. |
Type | Diagnostic Tool - Non-Imaging |
Current Stage Of Development | Early clinical assessment |
Year Development Stage Completed | 2019 |
Development Status | Under active development/distribution |
Impact | N/A |
Description | CarboMet Workshop |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Policymakers/politicians |
Results and Impact | CarboMet workshop on the availability and importance of carbohydrate standards and complex glycans. The aim was to gain insight from industry and academia on the uses and needs of carbohydrate standards and glycans within research and other fields. These are generally not widely available and therefore the information was to be fed back to the CarboMet network and politicians assoicated with this funding group to potentially gain money to fund projects to increase availability of glycan and carbohydrate standards. |
Year(s) Of Engagement Activity | 2019 |
Description | Eurocarb 2019 |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | International Carbohydrate conference in Leiden, Netherlands. Gave a poster presentation and recieved feedback and many questions from professionals and other students giving good insight into avenues to improve my work. I also gained insights into possible future work by viewing other work carried out by global research groups. |
Year(s) Of Engagement Activity | 2019 |
Description | Pharmacy Showcase |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Postgraduate students |
Results and Impact | Members of staff and ppoastgraduate students from the Department of Pharmacy at Reading attended a day of poster and oral presentations on the work being carried out by all PhD students. This events allows for the sharing of ideas across multiple disciplines within pharmaceutical research as well allowing for the generation of questions to drive new ideas and thoughts regarding each students work. In 2018 I presented a poster and in 2019 I have an oral presentation on the work carried out as part of my PhD. |
Year(s) Of Engagement Activity | 2018,2019 |
Description | Poster Presentation - RSC Carbohydrate Conference |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Professional Practitioners |
Results and Impact | RSC Carbohydrate Conference hosted at Reading. This gave the opportunity for the sharing of research in the field of carbohydrate research to a large group of in-.the-field professionals, as well as postgraduate and undergraduate students. I presented a poster at this conference on the current state of my work as of the conference in 2018. This allowed for me to gain feedback on my work. |
Year(s) Of Engagement Activity | 2018 |