Winner: 2021 Analytical Division Horizon Prize: Robert Boyle Prize for Analytical 新月直播app下载
NoseToDiagnose
For a novel approach to early Parkinson’s disease diagnosis and stratification using a simple non-invasive skin swab.
The NoseToDiagnose team has shown it is possible to identify Parkinson鈥檚 disease based on compounds found on the surface of skin. The findings offer hope that a pioneering new test could be developed to diagnose the degenerative condition through a simple painless skin swab.
Parkinson's disease is a condition in which parts of the brain become progressively damaged over many years, resulting in a range of physical and psychological symptoms. This team, led by scientists at The University of Manchester, have developed a technique which works by analysing compounds found in sebum (the oily substance that coats and protects the skin) to identify changes in people with Parkinson鈥檚 disease. Sebum is rich in lipid-like molecules and is one of the lesser studied biological fluids in the diagnosis of the condition.
The work began following the observation of Joy Milne, a retired nurse, whose husband was diagnosed with Parkinson鈥檚 at the age of 45. Joy has an incredible ability of using her sense of smell to distinguish Parkinson鈥檚 in individuals by detecting a distinctive 鈥渕usky鈥� odour, even before symptoms emerge in those affected.
With high resolution mass spectrometry, the team were able to profile the complex chemical signature in sebum of people with Parkinson鈥檚 and show subtle but fundamental changes as the condition progresses. These promising results could lead to a definitive 鈥榳orld first鈥� test to diagnose Parkinson鈥檚 accurately, speedily and cost effectively. The skin swab could also provide an incredibly important new tool in clinical trials, by helping researchers measure whether new, experimental treatments are able to slow, stop or reverse the progression of Parkinson鈥檚.
Working with the University of Manchester Innovation Factory, the team has patents filed for their diagnostic techniques and have created a spin-out company Sebomix Ltd. to commercialise the new tests.
We say we are led by the nose and we are, although all of this has been a route to exploring sebum which has been tremendously exciting because we believe sebum traps compounds. From the smell of new-born babies to the scent of second-hand clothes, we all have a knowledge that sebum has a smell or can trap smells, but Joy was the person who made us realise that this could be useful. When you think of it like that 鈥� you wonder why no one thought of it before.
Professor Perdita Barran
Perdita Barran, Chair of Mass Spectrometry and Director of the Michael Barber Centre for Collaborative Mass Spectrometry, University of Manchester
Rob DeBie, Professor of Movement Disorders, University of Amsterdam鈥檚 Faculty of Medicine (AMC-UvA)
Roy Goodacre, Chair in Biological Chemistry, University of Liverpool
Kat Hollywood, Senior Experimental Officer, University of Manchester
Tilo Kunath, Reader in Regenerative Neurobiology, University of Edinburgh
Sze Hway Lim, PhD Student and Junior Doctor, University of Manchester and Salford Royal Infirmary
Camilla Liscio, Senior Application Chemist, Anatune
Lesley-ann Miller, Manchester Institute of Biotechnology Operations Manager, University of Manchester
Joy Milne, Honorary Lecturer in Molecular Olfaction, University of Manchester
Anouk Rijs, Professor Analytics of Biomolecular Interactions, Vrije Universiteit Amsterdam
Depanjan Sarkar, Postdoctoral Research Associate, University of Manchester
Monty Silverdale, Consultant Neurologist and MAHSC Honorary Clinical Chair, Salford Royal Infirmary and University of Manchester
Eleanor Sinclair, Postdoctoral Research Associate, University of Manchester
Drupad Trivedi, CAMS Lecturer in Chemometrics, University of Manchester
Caitlin Walton-Doyle, PhD student, University of Manchester
Phine Woodward, Business Development Manager, Anatune
Yun Xu, Research Associate Biochemistry & Systems Biology, University of Liverpool
Q&A with NoseToDiagnose
Perdita Barran
Chair of Mass Spectrometry and Director of the Michael Barber Centre for Collaborative Mass Spectrometry, University of Manchester
What were the biggest challenges in this project?
So for me it was convincing funders to fund what we do, because it is so extraordinary. I wrote very big proposals initially and they just went nowhere. I switched to make a much smaller proposal to a small grant that鈥檚 run by the charity Parkinson鈥檚 UK and that was successful. Not only is this work so extraordinary, but I think it was also because we needed to establish ourselves. We now have three major publications and more coming, so that helps and I hope it will be easier next time!
What is the importance of collaboration in the chemical sciences?
It's what chemistry is all about. I used to say for a very long time that I鈥檓 a chemist who uses physics to understand biology. Chemistry is an extremely interdisciplinary science of its own: I have synthetic chemistry colleagues who are being really helpful about the sort of molecules we鈥檙e finding and how to analyse them better. I鈥檝e also had fantastic collaborations with neurology consultants as well as experts in the analysis of odours, mentoring us on the study design. It鈥檚 also been great to work with younger members of team 鈥� and for them to work with Joy 鈥� who brings joy to our work. Also the technical and support staff in our team, who keep the instruments running and have supported what we鈥檝e done. Also a final shout out to Anatune 鈥� when we first started, we didn鈥檛 have an instrument that would simultaneously measure the volatile components of the patient鈥檚 samples while allowing Joy to smell. They allowed us to go into their lab in Cambridge and to develop the instrument we needed. We鈥檝e collaborated with industry, medicine, young people, mature people, and foundations 鈥� all supported by our university.
Joy Milne
Lead Nose and Honorary Lecturer in Molecular Olfaction, University of Manchester
What does good research culture mean to you?
Looking at what we鈥檝e done and working with other people, I can see there is a good side to working with other companies, such as big pharma, but we鈥檇 like to see these companies speak to people living with Parkinson鈥檚. I give the example of big pharma producing a drug for Parkinson鈥檚 which grossly increases constipation. However, one of the first signs of Parkinson鈥檚 is increased constipation, which starts very early and lasts for the whole of the disease. A good research environment is one where there is an end-to-end approach.
How are the chemical sciences making the world a better place?
I was in the height of my career as a nurse when the first whitepaper on preventative medicine came out. The clinics were superb 鈥� looking at heart disease, diabetes etc., but since then, the NHS has become burdened by extra costs and strict processes of referrals. What I have seen from the testing is that this could be a tremendous help to an overburdened NHS, and when I was nursing, I did smell other diseases too. Some of the young people with Parkinson鈥檚 have spent ten years going from pillar to post before they are diagnosed and it鈥檚 the same with cancer, Alzheimer鈥檚 and diabetes. I think analytical chemistry has the ability to revive the NHS.
Monty Silverdale
Consultant Neurologist and MAHSC Honorary Clinical Chair, Salford Royal Infirmary and University of Manchester
Why is this so important and exciting?
As a Parkinson鈥檚 disease (PD) clinician, I feel there are 3 very novel and exciting results from this research study.
Firstly that we can distinguish PD from control fairly accurately using a simple skin swab. The possibility of using a simple cheap skin swab as an aid to helping PD diagnosis is a step closer. Clinical examination is only around 75% accurate when patients first present with mobility issues. Even then the disease process is known to already be very advanced. Currently available tests such as DAT scans are very expensive and not widely available.
Secondly that a simple skin swab may help gain pathophysiological insight into the neurodegenerative process in PD. Obviously this needs to be studied further but the initial results are very interesting in this regard.
Thirdly is the fact that we get such amazing information from swabbing sebum on the skin. We have never really used sebum as a diagnostic biofluid before and the possibilities (within and outwith PD) are enormous.
How are the chemical sciences making the world a better place?
It is extremely important for clinicians to collaborate with the chemical sciences. We are just chemistry. When we go wrong it is just chemistry. In the end I believe chemistry will be able to treat almost all human disease.
I feel very lucky to have worked with such a gifted, passionate and dedicated chemistry team on this collaborative project. Our teams consists of laboratory scientists, statisticians, clinicians and importantly people who have been affected by Parkinson鈥檚 disease.
Eleanor Sinclair
Postdoctoral Research Associate, University of Manchester
What was your role within the team?
I joined the team during the first year of my PhD research as an aspiring analytical chemist. My initial role was in study design alongside the generation and processing of (many) sampling kits. I have been the lead analytical scientist in the development of methods and strategies for the analysis of sebum for Parkinson鈥檚 disease diagnosis.
Our team encapsulates a variety of backgrounds and career stages from analytical scientists, bioinformaticians, experienced clinicians and medical researchers to an integral team member who has experienced first-hand the effect this disease has on a person and their family.
Why is this work so important?
Not only are we working with a biofluid that is not routinely used for medical diagnosis, but we are also investigating a disease that has so far evaded the development of a clinical diagnostic test. There has been a combination of striving to develop solutions to the analytical challenges associated with sebum, alongside those associated with a multifaceted disease such as Parkinson鈥檚 disease.