An Integrated platform for Quantitative Sterolomics: From Oxysterols to Bile Acids and Steroids

Lead Research Organisation: Swansea University
Department Name: Institute of Life Science Medical School

Abstract

Cholesterol is an essential component of every animal cell. It is a structural lipid in cell membranes and the precursor of oxysterols, bile acids and steroid hormones. Cellular cholesterol homeostasis is maintained by the balance between cholesterol absorption, biosynthesis and metabolism. The first step of all cholesterol metabolism is oxidation to an oxysterol. Oxysterols are oxygenated derivatives of cholesterol which in the past have been regarded as transport forms of cholesterol returning it to the liver for conversion to bile acids. However, recent data indicates that oxysterols have biological activity, mediating a number of cholesterol-induced metabolic effects. Furthermore, down-stream acidic cholesterol metabolites, biosynthesised by many different cell types, are also biologically active. New results show that oxysterols are involved in many areas of biology e.g. acting to reduce proliferation of progenitor cells in developing brain, reducing proliferation of naive B cells and blocking class switch recombination in the immune system, offering protection against neurodegenerative disease and memory loss, and showing differential expression in malignant cells. Furthermore, bile acids, recycled by the enterohepatic system, have been shown to act as hormones by activating the G protein coupled receptor TGR5 and triggering an increase in energy expenditure and attenuation of diet-induced obesity. It is important to realise that oxysterols are a class of molecule consisting of a wide-range of distinct chemical entities. This is also true of their down-stream metabolites, and is a consequence of the initial oxidation reaction occurring at any one of many potential sites on the cholesterol molecule and the order of subsequent enzymatic biotransformations being variable. This leads to a multitude of possible metabolites. This complexity is similarly reflected in bile acids which can be structurally-transformed by bacteria in the enterohepatic system. Cholesterol metabolites are challenging molecules to analyse in biological systems. This is a consequence of their low abundance against a high background of cholesterol (e.g. ng oxysterol / microg cholesterol in brain, ng bile acid / mg cholesterol in plasma, pg neurosteroid / microg cholesterol in CSF), the propensity of cholesterol to be oxidised in air to oxysterols (and also to C19 & C21 steroids) there-by generating analytical artefacts, and their lack of a strong chromophore but thermal lability. The consequence of this is that comprehensive cholesterol metabolite profiles are poorly described in body fluids, tissues and cell types. In this proposal we intend to meet this challenge by developing an integrated mass spectrometry-based platform for the ultra-high sensitivity quantitative and structural determination of cholesterol metabolites in biological systems. We will introduce new technology based on chemical-tagging to enhance the analysis of cholesterol metabolites, their structural determination, and quantification. By exploiting stable-isotope labelling in the charge-tags we will be able to determine absolute quantities of specific metabolites and also perform relative quantification of untargeted metabolites between different samples e.g. between different locations in brain or between different cell types. Through international collaboration we will investigate the biological activity of the identified metabolites in defined biological assays. This project is likely to have impact with respect to healthy aging, and as deranged cholesterol synthesis and metabolism is implicated in numerous disease states (neurodegenerative disease; atherosclerosis; diabetes) and malformation syndromes will be of benefit to UK pharma and those involved in biomarker discovery and clinical screening.

Technical Summary

The primary objective of the current proposal is to develop an integrated mass spectrometry (MS)-based platform for the quantitative and structural determination of cholesterol metabolites in biological systems. This will be supplemented by assays of their bioactivity. Over the last 20 years the focus of the PI's research has been the identification and quantification of oxysterols, bile acids and steroids in body fluids, tissues and cell types. While many molecules in these classes can be analysed at high sensitivity in targeted analysis by MS, usually utilising multiple reaction monitoring (MRM) or selected-ion recording (SIR), such analysis require pre-defined targets and are not suitable for profile analysis or the identification of unknown or unexpected components. Furthermore accurate quantification requires an isotope-labelled internal standard. In recent years we have developed an alternative strategy based on charge-tagging and LC-MSn for the ultra-high sensitivity identification and quantification of cholesterol metabolites. By utilising simple chemistry we tag a charged group to a ketone group on cholesterol metabolites, this improves the LC-MS response by two - three orders of magnitude. Further, the nature of the derivative enhances the information content of MSn spectra, allowing structure determination and identification of unknowns. In this proposal we seek to move this methodology to the next level by incorporating stable-isotope labelling in the charge-tag thereby allowing absolute quantification of individual samples and relative quantification between samples. Further, we will extend the number of metabolites amenable to charge-tagging by incorporating enzymatic conversion of alcohol functions to ketone groups (thus available for derivatisation).

Planned Impact

The primary objective of the current proposal is to develop an integrated mass spectrometry (MS)-based platform for the quantitative and structural determination of cholesterol metabolites in biological systems. As part of this proposal we will create a series of isotope-coded charge tags for use in ultra-high sensitivity quantitative studies. The isotope-coded charge tags will offer improved analyte sensitivity and allow absolute quantification of defined analytes and relative quantification (between samples) of undefined targets. We will further develop the tagging chemistry to allow charge-tagging to alcohol (3beta and 3alfa hydroxyl groups on the steroid skeleton) functionalities in addition to oxo (ketone/aldehyde) groups. Although in this study we will concentrate our attention on the analysis of cholesterol metabolites, the developed isotope-coded charge tags will be equally useful in other areas of lipidomics and metabolomics. The likely beneficiaries of our analytical platform are analysts working in the areas of metabolomics, lipidomics, biomarker discovery, clinical screening and doping control. The methods generated by the present study will be valuable to those working in the sterol bile acid and steroid fields, including contract research, pharmaceutical companies, and doping and clinical laboratories. The analytical methods are likely to be important in neuroscience, particularly for the prediction and monitoring of neurodegenerative disease, and in stem cell biology, cancer and immunology where specific cholesterol metabolites have been shown to be important in influencing cell proliferation. We will publish our data in peer review journals, make presentations at international meetings and also establish a website where data and methods will be freely available. We will also present our data to the general public at public seminars, open days and visits to schools. With respect to commercialisation we are collaborating with Proteome Sciences plc in the area of isotope-coded tags for tandem mass spectrometry in metabolomics, and we would negotiate with them to commercialisation our isotope-coded charge tags. The research has considerable potential impact on the nation's health and wellbeing. We plan (in future studies) to utilise our analytical platform to validate potential cholesterol derived metabolites as markers for the early diagnosis of Alzheimer's disease. Early diagnosis will be important as new treatments; both pharmacological and psychological are being developed. The research may also have an impact in the development of regenerative therapies for Parkinson's disease as cholesterol metabolites have been found to be important in the development of dopaminergic neurons from stem cells. The PDRA employed in this project will gain an expert education in biological mass spectrometry; which can in the future be exported to all areas of analytical science. Further, the project is at the interface of chemistry, biology and medicine and is thus multidisciplinary. Cholesterol metabolites identified to have biological activity will be patented in association with Swansea University. We will seek to exploit commercially our isotope-coded charge tags in collaboration with Proteome Sciences plc.

Publications

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Abdel-Khalik J (2017) Defective cholesterol metabolism in amyotrophic lateral sclerosis. in Journal of lipid research

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Chen Y (2013) Shotgun cholanomics of ileal fluid. in Biochimie

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Crick PJ (2015) Quantitative charge-tags for sterol and oxysterol analysis. in Clinical chemistry

 
Description Below we describe the objectives of the project and the progress made:
A. Create a series of isotope-coded charge tags for use in ultra-high sensitivity quantitative (absolute and relative) lipidomics. We have achieved this objective and applied for a patent:- "Kit and method for quantitative detection of steroids" Application No. GB1215924.0. We have described the method at international meetings (2nd ENOR Symposium, Oxysterols and Related Sterols in Chemistry, Biology and Medicine, Dijon 20-21 September 2012; and 20th International Mass Spectrometry Conference, Geneva, August 24-29, 2014). The method is published in Clinical Chemistry 2014.
B. Exemplify the developed LC-MSn platform in the discovery and quantification of oxysterols/bile acids/steroids in biological fluids, tissues and specific cells types. Through collaboration with clinicians we have exploited our methodology in the comprehensive profiling of plasma sterols, with particular reference to inborn errors of metabolism. We have used the method to provide biochemical support to our discovery that chenodeoxycholic acid can be successfully used in the treatment of oxysterol 7alpha-hydroxylase deficiency. In collaboration with a pharmaceutical company we performed similar studies on cerebrospinal fluid (CSF) from patients suffering neural inflammation. We have further exploited our methodology for oxysterol analysis in tissues and in virus infected cells. This work has resulted in publications in Journal of Lipid Research, Journal of Inherited Metabolic Disease and in the journal Immunity. We have

C. Generate a LC-MSn library of charge-tagged oxysterols/bile acids/steroids for use by the lipidomic and metabolomic communities. The library can be found at http://sterolanalysis.org.uk/?page=Home

D. Through collaboration with colleagues in Karolinska Institutet we investigate whether the identified compounds activate nuclear receptors in relevant cell systems. In collaboration with colleagues in Karolinska Institutet we have identified cholic acid as a new LXR ligand in brain and 24S,25-epoxycholesterol as the most abundant LXR ligand in developing mouse midbrain. Notably, each ligand selectively regulated the development of distinct midbrain neuronal populations. Whereas cholic acid increased survival and neurogenesis of Brn3a-positive red nucleus neurons, 24S,25-epoxycholesterol promoted dopaminergic neurogenesis. These results identify an entirely new class of highly selective and cell type-specific regulators of neurogenesis and neuronal survival. Moreover, 24S,25-epoxycholesterol promoted dopaminergic differentiation of embryonic stem cells, suggesting that LXR ligands may thus contribute to the development of cell replacement and regenerative therapies for Parkinson's disease. This study was published in the journal Nature Chemical Biology. In a related study on human we have identified 3ß,7a-dihydroxycholest-5-en-26-oic acid as an LXR ligand which promotes the survival of oculomotor neurons. We have made a patent application "Compound and Method for the Treatment of Neurodegenerative Conditions" Application No. GB1303589.4 to protect these discoveries. The study is published in the Journal of Clinical Investigation.
Exploitation Route 1. We have collaborated with a pharmaceutical company on a project where our isotope-coded charge tags were directly utilized. 2. We have licenced our isotope-coded charge tags to Avanti Polar Lipids Inc and to Cayman Chemical Company. 3. The discovery of LXR ligands as cell type-specific regulators of neurogenesis and neuronal survival may lead to potential treatments for conditions such as Parkinson's disease and motor neuron disease. 4. To-date, the key activity towards exploiting the impact of our discoveries is through the patent applications "Kit and method for quantitative detection of steroids" and "Compound and Method for the Treatment of Neurodegenerative Conditions". 5. Our discovery of chenodeoxycholic acid as a treatment for oxysterol 7alpha-hydroxylase deficiency has lead to the initiation of clinical trials. 6. We have discovered a novel modulators for the Hedgehog signalling pathway.
Sectors Agriculture, Food and Drink,Chemicals,Healthcare,Pharmaceuticals and Medical Biotechnology

URL https://www.swansea.ac.uk/staff/medicine/research/griffithswj/
 
Description The findings from this study have resulted in five patent applications 1. "Kit and method for quantitative detection of steroids" Application No. GB1215924.0; 2. "Compound and Method for the Treatment of Neurodegenerative Conditions" Application No. GB1303589.4; 3. "Deuterated compounds" Application No. GB 1316050.2; 4."Diagnostic methods and kits" Application No. GB1516441.1. 5. "Diagnostic Methods and Kits" Application No.GB2016/052710. Our discovery of chenodeoxycholic acid as a treatment for oxysterol 7alpha-hydroxylase deficiency has prompted clinical trials. The methodology developed in this award is being used to support the clinical trials. The "Kit" has been licenced to Avanti Polar Lipids Inc and Cayman Chemical Company.
First Year Of Impact 2013
Sector Agriculture, Food and Drink,Chemicals,Healthcare,Pharmaceuticals and Medical Biotechnology
Impact Types Economic

 
Description A4B
Amount £66,240 (GBP)
Organisation Welsh Assembly 
Sector Public
Country United Kingdom
Start 04/2014 
End 12/2014
 
Description A4B
Amount £378,057 (GBP)
Funding ID HE09161003 
Organisation Government of Wales 
Sector Public
Country United Kingdom
Start 10/2013 
End 12/2014
 
Description BBSRC Responsive mode
Amount £460,386 (GBP)
Funding ID BB/N015932/1 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 10/2016 
End 09/2019
 
Description Follow on Fund
Amount £10,954 (GBP)
Funding ID BB/FOF/PF/15/13 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 09/2013 
End 03/2014
 
Description KESS II
Amount £53,476 (GBP)
Funding ID EGR817 
Organisation Government of Wales 
Sector Public
Country United Kingdom
Start 10/2016 
End 09/2019
 
Description Life Sciences Research Network Wales
Amount £50,000 (GBP)
Organisation Government of Wales 
Sector Public
Country United Kingdom
Start 03/2015 
End 02/2016
 
Description Michael J. Fox Foundation's Targeted RFA (Lipidomics)
Amount $376,119 (USD)
Funding ID 16231 
Organisation Michael J Fox Foundation 
Sector Charity/Non Profit
Country United States
Start 06/2019 
End 05/2021
 
Description Responsive
Amount £652,000 (GBP)
Funding ID BB/K019112/1 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 07/2013 
End 06/2016
 
Description Responsive Mode
Amount £382,198 (GBP)
Funding ID BB/L001942/1 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 01/2014 
End 01/2017
 
Description SHIPP INITIATIVE
Amount £36,000 (GBP)
Funding ID SHIPP-0001 
Organisation Government of Wales 
Sector Public
Country United Kingdom
Start 07/2016 
End 02/2017
 
Title EADSA 
Description We have developed a charge-tagging approach to greatly enhance mass spectrometry sensitivity for biomolecule analysis. 
Type Of Material Technology assay or reagent 
Year Produced 2011 
Provided To Others? Yes  
Impact Allowed the identification of novel cholesterol metabolites in biological systems. 
 
Description CHORI: Inborn errors of metabolism 
Organisation Children's Hospital Oakland Research Institute (CHORI)
Country United States 
Sector Hospitals 
PI Contribution Analysis of patient and mouse model samples.
Collaborator Contribution Provision of patient and mouse model samples. Expertise in inborn errors of metabolism.
Impact Three publications
Start Year 2007
 
Description Cardiff LipidMaps 
Organisation Cardiff University
Country United Kingdom 
Sector Academic/University 
PI Contribution Expert input on sterol biochemistry.
Collaborator Contribution Expert input on lipid biochemistry
Impact Revision of lipid nomenclature.
Start Year 2017
 
Description Edin 
Organisation University of Edinburgh
Country United Kingdom 
Sector Academic/University 
PI Contribution We have provided intellectual input and data.
Collaborator Contribution Edinburgh has provided intellectual input and data.
Impact Paper in Immunity and PLoS Biology
Start Year 2012
 
Description Hereditary Spastic Paraplegia 
Organisation Eberhard Karls University of Tubingen
Department Centre of Neurology and Hertie-Institute for Clinical Brain Research
Country Germany 
Sector Academic/University 
PI Contribution Expertise in oxysterol and sterol analysis.
Collaborator Contribution Hepatocyte and cortical neuron differentiation from iPS cells. Clinical samples from patients with in born errors of metabolism
Impact Publication in The Journal of Clinical Investigation 2014
Start Year 2014
 
Description ICH: Inborn errors of metabolism 
Organisation University College London
Department Institute of Child Health
Country United Kingdom 
Sector Academic/University 
PI Contribution Investigation of inborn errors of cholesterol biosynthesis and metabolism.
Collaborator Contribution Clinical information concerning inborn errors of metabolism
Impact Four publications
Start Year 2009
 
Description Karolinska 
Organisation Karolinska Institute
Country Sweden 
Sector Academic/University 
PI Contribution We have brought essential data and insight to the collaboration. We are bringing new technology
Collaborator Contribution They have brought essential data and insight to the collaboration. Our partners are bringing transgenic animal material and expertise to the collaboration.
Impact This is a multidisciplinary collaboration between neuroscientists and clinical chemists at Karolinska Institute and analytical scientists in Swansea. This colaboration has resulted in papers in Nature Chemical Biology and the Journal of Clinical Investigation.
Start Year 2006
 
Description Manchester: Collaboration on inborn errors of metabolism 
Organisation University of Manchester
Country United Kingdom 
Sector Academic/University 
PI Contribution Analysis of plasma and urine samples in the study of inborn errors of cholesterol biosynthesis and metabolism.
Collaborator Contribution Provision of samples for the study of inborn errors of cholesterol biosynthesis and metabolism.
Impact Three papers have been published
Start Year 2012
 
Description Motor Neuron Disease 
Organisation University of Oxford
Department Nuffield Department of Clinical Neurosciences
Country United Kingdom 
Sector Academic/University 
PI Contribution Expertise in sterol and oxysterol analysis
Collaborator Contribution Expertise in motor neuron disease clinical pathology
Impact Publication in Journal of Lipid Research 2017
Start Year 2014
 
Description Multiple Sclerosis 
Organisation University Hospital Basel
Country Switzerland 
Sector Hospitals 
PI Contribution Expertise in sterol and oxysterol analysis.
Collaborator Contribution Expertise in multiple sclerosis pathology
Impact Publications in The Journal of Clinical Investigation (2014) and Molecular Neurobiology (2016)
Start Year 2014
 
Description Peroxisome 
Organisation University of Leuven
Department Zoological Institute
Country Belgium 
Sector Academic/University 
PI Contribution Expertise in sterol and oxysterol analysis
Collaborator Contribution Expertise in biochemistry of the peroxisome
Impact Publications in Steroids (2015), Biochemical Journal (2014)
Start Year 2014
 
Description Pulmonary Fibrosis 
Organisation University of Glasgow
Department College of Arts
Country United Kingdom 
Sector Academic/University 
PI Contribution Expertise in sterol/oxysterol analysis
Collaborator Contribution Expertise in the pathology of pulmonary fibrosis
Impact Publication in Journal of Allergy and Clinical Immunology (2016)
Start Year 2014
 
Description SPG5 at Athens Medical Center 
Organisation Athens Medical Center
PI Contribution Analysis of plasma and urine samples from SPG5 patients under a new treatment regime.
Collaborator Contribution Disease diagnosis. Treatment of patients.
Impact Manuscript submitted. Collaboration between Medicine and Bioanalysis.
Start Year 2015
 
Description University of Houston 
Organisation University of Houston
Country United States 
Sector Academic/University 
PI Contribution Analysis of human and transgenic mouse material.
Collaborator Contribution Provision of human and transgenic mouse material.
Impact Three publications.
Start Year 2013
 
Description Zurich 
Organisation University Hospital Zurich
Country Switzerland 
Sector Hospitals 
PI Contribution Analysis of tissue and blood samples from human and mouse samples.
Collaborator Contribution Provision of human and mouse samples.
Impact Manuscript in preparation. Multi-disciplinary- Medicine, analytical biochemistry
Start Year 2016
 
Title Compound and method for the treatment of neurodegenerative conditions 
Description The present invention relates to a compound and method for the treatment of neurodegenerative conditions and in particular but not exclusively to the use of a cholestenoic acid to treat neurodegenerative conditions such as Parkinson's disease and motor neuron disease. 
IP Reference WO2014132052 
Protection Patent application published
Year Protection Granted 2014
Licensed No
Impact Impact has yet to arrive.
 
Title DEUTERATED COMPOUNDS 
Description Compounds of general formula (I) wherein (I) R1 - R4 are each independently selected from H and deuterium; and at least one of R1 - R4 is deuterium. The compounds have been found to be particularly useful for treating neurodegenerative conditions and in particular but not exclusively conditions such as motor neurone disease. 
IP Reference WO2015036726 
Protection Patent application published
Year Protection Granted 2015
Licensed No
Impact Impact has yet to arise.
 
Title DEUTERATED COMPOUNDS 
Description Compounds of general formula (I) wherein (I) R1 - R4 are each independently selected from H and deuterium; and at least one of R1 - R4 is deuterium. The compounds have been found to be particularly useful for treating neurodegenerative conditions and in particular but not exclusively conditions such as motor neurone disease. 
IP Reference WO2015036726 
Protection Patent granted
Year Protection Granted 2015
Licensed No
Impact Spinout company formed.
 
Title Diagnostic methods and kits 
Description Diagnostic method for identification of an inborn error of cholesterol biosynthesis. 
IP Reference GB1611636.0 
Protection Patent application published
Year Protection Granted 2016
Licensed No
Impact Patent application has been made.
 
Title KIT AND METHOD FOR QUANTITATIVE DETECTION OF STEROIDS 
Description The invention relates to a kit and methods for quantitative detection of steroids in a sample. The kit comprises quantitative charge tags and an oxidising agent. 
IP Reference WO2014037725 
Protection Patent application published
Year Protection Granted 2014
Licensed Yes
Impact The kit will be commercialised by Avanti Polar Lipids
 
Title KIT AND METHOD FOR QUANTITATIVE DETECTION OF STEROIDS 
Description The invention relates to a kit and methods for quantitative detection of steroids in a sample. The kit comprises quantitative charge tags and an oxidising agent. 
IP Reference WO2014037725 
Protection Patent granted
Year Protection Granted 2014
Licensed Yes
Impact Licence to Avanti Polar Lipids Inc. Licenced to Cayman Chemical Company
 
Title KIT AND METHOD FOR QUANTITATIVE DETECTION OF STEROIDS 
Description The present invention relates to a kit for the quantitative detection of steroids and to methods for using the kit. In particular, the method relates to a kit which enables steroids to be quantitatively detected using mass spectrometry. 
IP Reference GB1215924.0 
Protection Patent application published
Year Protection Granted
Licensed No
Impact The discovery has been exploited for academic work.
 
Title CYP7B1 
Description The drug is in clinical trials. 
Type Therapeutic Intervention - Drug
Current Stage Of Development Early clinical assessment
Year Development Stage Completed 2016
Development Status Under active development/distribution
Clinical Trial? Yes
Impact The drug is in clinical trials for the treatment of a rare disease. 
URL https://clinicaltrials.gov/show/NCT02314208
 
Title Diagnostic test 
Description Diagnostic test for inborn errors of cholesterol biosynthesis and metabolism. Seeking support to develop the test further. 
Type Diagnostic Tool - Non-Imaging
Current Stage Of Development Initial development
Year Development Stage Completed 2018
Development Status Actively seeking support
Impact Used to monitor response to treatment. 
 
Company Name Cholestenix 
Description The Technology Swansea Innovations has developed an integrated Mass Spectroscopy (MS) platform for the quantitative and structural determination of cholesterol metabolites in biological systems. The Liquid Chromatography (LC) MS technology utilises quantitative charged tags that allows for the identification of steroid molecules. The technology is substantially more sensitive than existing methodologies with a capacity to quantify a greater number of steroids. The Science The research group at Swansea Innovations have established that endogenous acidic cholesterol metabolites can have a neuroprotective and a neurotoxic effect on motor neurons. The Market Swansea inventors have focussed on the medical opportunities for this technology as they have identified acidic cholesterol metabolites with neuroprotective activity and also abnormal cholesterol metabolite levels in a range of neurodegenerative diseases. Cerebrotendinous xanthomatosis (CTX) is an inherited disease in which affected individuals cannot make the normal profile of bile acids. As children grow older they may present with a range of symptoms including cataracts, abnormal movements, intellectual disability and cholesterol deposits in the brain. In conjunction with the Karolinska Institutet in Sweden, Swansea researchers have shown that plasma samples from patients with CTX showed very low levels of all cholestenoic acids. Further, abnormal cholesterol profiles have been identified in the Motor Neuron Disease (MND)- related illness, hereditary spastic paresis. A spin out company CholesteniX has been formed to commercialise the biomarker and therapeutic potential of this technology for MND and other neurodegenerative diseases. Swansea is in discussions with a number of commercial parties who have expressed an interest in this technology. The consensus view now is that most neurodegenerative diseases (e.g. Alzheimer's and Parkinson's disease) may be developing for anything up to decades before physical symptoms start to appear. Early diagnosis and treatment in this area may hold out the hope of slowing progression sufficiently to avoid late stage disease, saving the NHS and the economy millions of pounds in treatment and care and benefiting many thousands families with affected individuals. 
Year Established 2013 
Impact none as yet
 
Description ASBMB Cholesterol and ALS 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Article in ASBMB monthly magazine
Year(s) Of Engagement Activity 2016
 
Description Cholesterol and ALS 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Media (as a channel to the public)
Results and Impact Press release to communicate latest scientific discovery. Many email responses from motor neuron disease sufferers or carers.
Year(s) Of Engagement Activity 2016
 
Description Cholesterol metabolites regulate motor neuron function 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact A research highlight was published in Nature Reviews Endocrinology.

NA
Year(s) Of Engagement Activity 2014
URL http://www.nature.com/nrendo/journal/vaop/ncurrent/full/nrendo.2014.184.html
 
Description New steroid discovery could improve Parkinson's treatment; 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Scientists at Swansea University and Karolinska Institutet in Stockholm have identified two steroid-type molecules that play an important role in the survival and production of nerve cells in the brain.



The discovery, published in the journal Nature Chemical Biology, could help in the development of new treatments for neurological diseases such as Parkinson's disease.

no actual impacts realised to date
Year(s) Of Engagement Activity 2013
 
Description Steroids: Scientists examine controversial substance's potential to treat Parkinson's, http://www.walesonline.co.uk/news/wales-news/steroids-scientists-examine-controversial-substances-2496776 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Steroids could be used to treat a debilitating disease that affects thousands in Wales today. Researchers at a University in Wales have highlighted the controversial substance's positive side after discovering two steroid type molecules that could treat Parkinson's disease

no actual impacts realised to date
Year(s) Of Engagement Activity 2013