Latest news with #MichaelJFoxFoundation
Forbes
27-05-2025
- Business
- Forbes
Sergey Brin's Latest Stock Gift Signals Shift In Philanthropic Strategy
Google cofounder Sergey Brin is back in the office working on AI. But he's also ramping up his philanthropic investments, largely centering conditions of the central nervous week Google cofounder Sergey Brin gave away $700 million worth of Alphabet shares. The gifts were split between three nonprofits, according to a representative of Brin's family office. Nearly 80% of the shares—worth nearly $550 million—went to Brin's four-year-old nonprofit Catalyst4, while the remaining shares went to the Sergey Brin Family Foundation (14%) and Michael J. Fox Foundation (7%), which supports research and treatments for Parkinson's disease. Brin, 51, is worth an estimated $137 billion and is the world's eighth richest person. He's the largest individual donor—at more than $1.5 billion—to research on Parkinson's disease, which afflicted his mother, who died last year, and for which he has a genetic mutation that means he has a much higher chance of getting the disease than the general population. And he's made a big commitment to fund research into the causes of bipolar disorder and autism, as Forbes wrote about in February. Brin's team has created an umbrella group to oversee research in these areas called CNS Quest. (CNS stands for 'central nervous system.) His significant gift of Alphabet shares to Catalyst4 will, in large part, power the work of the CNS Quest, per Brin's representative. Brin sees his philanthropic mission as deeply 'personal because it starts with Parkinson's disease, and I carry one of the genetic mutations discovered, the G2019S mutation to the LRRK2 gene,' he wrote to Forbes in February. He keeps his life private, but all three conditions under the CNS Quest have affected members of his family. Brin's increased giving to Catalyst4, a type of nonprofit called a 501(c)(4) that can lobby as well as own entire for-profit companies, may be part of a broader shift in his giving strategy. To date, Brin has donated at least $1.5 billion to Catalyst4. In late 2021, Brin seeded the entity with more than $450 million worth of donated Alphabet and Tesla stock, and added another $615 million in 2023. Catalyst4 is still smaller than Brin's decade-old, more traditional nonprofit, the Sergey Brin Family Foundation, which had $4 billion in assets as of the end of 2023. But in recent years he's been giving more to Catalyst4 than to his family foundation, which also funds various climate and education initiatives. With Catalyst4, Brin hopes that his efforts can address both basic science research and eventual treatments and therapies; the latter most often comes from for-profit companies. 'What we've learned and seen from our other initiatives is that it's really important to fund both things in parallel, and have that feedback loop across both the science and the clinical side of things, like trial design, drug development and therapeutics,' Ekemini Riley, who has a PhD in molecular medicine and helps lead the CNS Quest initiatives, told Forbes in February. In some cases, this means investing in biopharma companies through Catalyst4. Brin has been backing startups and venture capital funds that are working on for-profit solutions and treatments, investing more than $600 million to date, including about $400 million in 2024 alone. Per nonprofit tax filings, Catalyst4's portfolio includes a majority stake in biopharma firm MapLight, which is developing treatments for brain diseases and autism. MapLight is currently enrolling patients in Phase 2 clinical trials for a drug candidate that aims to help with 'social communication deficits' in certain autistic people. In February, Catalyst4 also led an $80 million funding round in Stellaromics, which makes detailed three-dimensional maps of gene activity in slices of tissue for other companies to use in drug development. Any profits from investments must be reinvested into the nonprofit, and Catalyst4 has given some portfolio companies 'philanthropic dollars' (often some 25% of the total investment) along with its equity investment, according to a person familiar with Brin's philanthropy. It's still unclear how exactly Brin will use his latest gift to further the goals of the CNS Quest and Catalyst4. But the ramp-up will certainly continue, especially crucial as the Trump administration continues to cut funding for medical research and clinical trials.
Yahoo
13-05-2025
- Health
- Yahoo
First patients dosed in final cohort of Phase 1b clinical trial of HER-096 for Parkinson's disease
Herantis Pharma Plc – Press release First patients dosed in final cohort of Phase 1b clinical trial of HER-096 for Parkinson's disease HER-096 is a first-in-class agent in development for the treatment of Parkinson's disease with disease modifying potential and convenient subcutaneous administration Successful completion of the first patient cohort in Part 2 of the trial and approval to proceed from the Data and Safety Monitoring Board Primary objective is to assess the safety, tolerability and pharmacokinetics of repeated subcutaneous doses of HER-096; the trial will also evaluate selected biomarkers, discover and identify novel treatment response biomarkers and monitor symptoms associated with Parkinson's disease Topline data from Phase 1b trial is expected in September 2025 Trial funded by the Michael J. Fox Foundation for Parkinson's Research (MJFF) and Parkinson's UK Espoo, Finland, 13 May 2025: Herantis Pharma Plc ("Herantis"), a company developing disease-modifying therapies for Parkinson's disease, today announced the first patients have been dosed in the final cohort of its Phase 1b clinical trial evaluating the safety and tolerability of HER-096 in patients with Parkinson's disease. Commenting on the study Antti Vuolanto, CEO of Herantis Pharma said: 'Parkinson's disease is a life altering condition, and there is an urgent need for new treatments that can halt or slow its progression. We are highly encouraged by the potential of HER-096. Its disease-modifying properties combined with its ability to cross the blood-brain barrier makes it a compelling candidate to become a transformative therapy for Parkinson's that addresses the underlying disease, not just the symptoms. We remain focused on completing the final cohort of this Phase 1b trial and expect to report topline data in September 2025.' Parkinson's disease is a devastating neurological condition affecting around 10 million people worldwide, for which there is currently no cure. Existing treatments only address the symptoms and are often associated with significant side effects. HER-096 is a first-in-class synthetic peptidomimetic designed to mimic the activity of cerebral dopamine neurotropic factor (CDNF) protein, with the capability of effectively crossing the blood-brain barrier allowing for convenient subcutaneous administration. With a multi-modal mechanism of action, HER-096 has the potential to protect against the neuronal degeneration and cell death that cause the symptoms of Parkinson's disease. About the Phase 1b study The Phase 1b clinical study consists of two parts. In Part 1, eight healthy volunteers received a single 300 mg subcutaneous dose of HER-096 to assess its safety and pharmacokinetic properties. Encouraging pharmacokinetic data from this phase were announced on 28 January 2025 here Part 2 is a randomized, double-blind, placebo-controlled part of the trial in patients with Parkinson's disease, divided into two cohorts. In the first cohort, 12 patients were dosed twice weekly over a four-week period. Of these eight patients received 200 mg of HER-096 and four received placebo. Based on a review of the data, the Data and Safety Monitoring Board (DSMB) recommended proceeding to the final cohort. In the final cohort, patients will receive 300 mg doses of HER-096 or placebo twice weekly over a four-week period. The primary objective of the Phase 1b trial is to assess the safety, tolerability and pharmacokinetics of repeated subcutaneous doses of HER-096. Part 2 will also evaluate selected biomarkers and aims to identify novel treatment-response biomarkers in patients with Parkinson's disease. Symptom progression will be monitored using both Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS) and with a wearable recording device. Topline results are expected in September 2025. This trial is funded by The Michael J. Fox Foundation for Parkinson's Research (MJFF) and Parkinson's UK. It is being conducted in Turku and Helsinki, Finland by the contract research organization Clinical Research Services Turku – CRST Oy. The Phase 1b trial builds on positive results from the Phase 1a trial, which demonstrated a good safety and tolerability profile, along with effective blood-brain barrier penetration of subcutaneously administered HER-096 in healthy volunteers. More information about the trial can be found on the website: The trial is registered at here: About HER-096 HER-096 is an engineered peptidomimetic molecule designed to mimic the activity of CDNF, a protein that promotes cell survival and functional recovery of neurons. HER-096 modulates the Unfolded Protein Response (UPR) pathway, which plays a critical role in restoring the cell protein balance (proteostasis) and preventing the processes leading to cytotoxic protein aggregation and neuronal cell death in the brain. In addition, HER-096 reduces inflammation in the affected brain area and can effectively pass the blood-brain barrier enabling convenient subcutaneous administration. With its multimodal mechanism of action, HER-096 has the potential to stop the progression of Parkinson's disease and significantly improve patients' quality of life. For more information, please contact: Tone Kvåle, CFOTel: +47 915 19576Email: ir@ ICR Healthcare Mary-Jane Elliott, Sarah Elton-Farr, Stephanie CuthbertTel: +44 20 3709 5700Email: herantispharma@ Certified Advisor: UB Corporate Finance LtdTel.: +358 9 25 380 225E-mail: ubcf@ About Herantis Pharma Plc Herantis Pharma Plc is a clinical-stage biotechnology company developing disease modifying therapies for Parkinson's disease. Herantis' lead product HER-096, is an advanced small synthetic chemical peptidomimetic molecule developed based on the active site of the CDNF protein. It combines the compelling mechanism of action of CDNF with the convenience of subcutaneous administration. The primary aim of the ongoing Phase 1b clinical trial is to show that repeated subcutaneous doses of HER-096 are safe and well-tolerated in patients with Parkinson's disease. The Phase 1a clinical trial demonstrated a good safety and tolerability profile, and efficient blood-brain barrier penetration of subcutaneously administered HER-096 in healthy volunteers. Herantis is listed on the Nasdaq First North Growth Market Finland. Company website: Forward-looking statements This release includes forward-looking statements which are not historical facts but statements regarding future expectations instead. These forward-looking statements include without limitation, those regarding Herantis' future financial position and results of operations, the Company's strategy, objectives, future developments in the markets in which the Company participates or is seeking to participate or anticipated regulatory changes in the markets in which the Company operates or intends to operate. In some cases, forward-looking statements can be identified by terminology such as 'aim,' 'anticipate,' 'believe,' 'continue,' 'could,' 'estimate,' 'expect,' 'forecast,' 'guidance,' 'intend,' 'may,' 'plan,' 'potential,' 'predict,' 'projected,' 'should' or 'will' or the negative of such terms or other comparable terminology. By their nature, forward-looking statements involve known and unknown risks, uncertainties and other factors because they relate to events and depend on circumstances that may or may not occur in the future. Forward-looking statements are not guarantees of future performance and are based on numerous assumptions. The Company's actual results of operations, including the Company's financial condition and liquidity and the development of the industry in which the Company operates, may differ materially from (and be more negative than) those made in, or suggested by, the forward-looking statements contained in this company release. Factors, including risks and uncertainties that could cause these differences include, but are not limited to risks associated with implementation of Herantis' strategy, risks and uncertainties associated with the development and/or approval of Herantis' drug candidates, ongoing and future clinical trials and expected trial results, the ability to commercialize drug candidates, technology changes and new products in Herantis' potential market and industry, Herantis' freedom to operate in respect of the products it develops (which freedom may be limited, e.g., by competitors' patents), the ability to develop new products and enhance existing products, the impact of competition, changes in general economy and industry conditions, and legislative, regulatory and political factors. In addition, even if Herantis' historical results of operations, including the Company's financial condition and liquidity and the development of the industry in which the Company operates, are consistent with the forward-looking statements contained in this company release, those results or developments may not be indicative of results or developments in subsequent in retrieving data Sign in to access your portfolio Error in retrieving data Error in retrieving data Error in retrieving data Error in retrieving data
Yahoo
20-03-2025
- Health
- Yahoo
The woman who can smell Parkinson's disease
Joy Milne's life has changed immeasurably since the day she ambushed an eminent stem-cell biologist at a talk in Edinburgh, dumbfounding him by asking why smell wasn't used to detect Parkinson's, when she had noticed a distinctive change to the odour of her husband, Les, more than a decade before his diagnosis. For one thing, there's the post: T-shirts – all of them worn so some presumably extremely ripe – from 'Argentina, all over the world', which arrive at the 75-year-old former nurse's cottage in Perth. They're sent by desperate people who've read about Milne's incredible diagnosing nose and want her to have a sniff, to put them out of unhappy limbo. For the record, she no longer opens the packages: 'It would not be ethical.' Then there's the work, which for Milne and her collaborator Professor Perdita Barran has mushroomed in a previously unimaginable number of directions, many of them frontier-smashing. The two have worked together since 2013 when Barran, a chemist now at the University of Manchester, was asked to help with a pilot study to test Milne's claim that she could smell Parkinson's. Milne was asked to sniff and pronounce on a set of T-shirts that had been worn overnight, either by a Parkinson's sufferer or by a control (hence the unusual mailbag). She aced the test, making just one mistake by assigning a control-group shirt to the Parkinson's group. Or, rather, two mistakes: the 12 T-shirts had been cut in half to create a larger dataset and Milne put both halves of this shirt in the Parkinson's group. Nine months later, its wearer reported that they, too, had been diagnosed. Milne hadn't just got every diagnosis correct, she had outperformed the medical establishment. Parkinson's is the fastest-growing neurological disorder in the world, and the second most common neurodegenerative disease after Alzheimer's. It is characterised by the progressive loss of dopamine-producing neurons in a part of the midbrain called the substantia nigra, which is associated with movement and muscle tone. Crucially, however, the disorder is not typically diagnosed until 60 to 80 per cent of those neurons have already been lost. The Michael J Fox Foundation has co-ordinated a multimillion-dollar investment in the search for a biomarker that could indicate the early presence of Parkinson's, in 2023 announcing that a method had been found to detect an abnormal protein in the spinal fluid (which requires a lumbar puncture to test). Thanks to Milne's nose, Barran has been able to analyse many small-molecule markers and she is 'very close' to a simple, non-invasive skin-swab test of clinical utility for a 'timely diagnosis', expected to undergo trials at Manchester's Wythenshawe Hospital later this year. As Barran is all too aware, a 'timely' diagnosis is seen as something of a mixed blessing given the current lack of treatments to slow or stop the progression of the disease. But many sufferers and their relatives (Milne among them) say their lives would have been easier had they understood, sooner, what was happening to them. Further, the identification of a set of biomarkers for early-stage Parkinson's is likely to accelerate and target the treatment options in development. Barran is also about to publish a paper about her work with Dr Claire Guest at Medical Detection Dogs, who trains dogs to detect the olfactory signals of cancer and, now, Parkinson's. 'The best dog, a golden retriever and Labrador cross called Peanut, was about as good as Joy,' says Barran. Guest explains, 'The learnings from the study we hope to apply to artificial intelligence and electronic noses in the future.' Beyond Parkinson's, research that arose with Milne's nose also has implications for the potential identification and treatment of other diseases by bringing into the spotlight a bodily fluid usually overlooked as a diagnostic: sebum. I meet Barran and Milne in the car park of Manchester Piccadilly station on a freezing day in February. Barran is stylish and crisply intelligent, navigating the rush-hour traffic in her canary-yellow car while giving a commentary on the history of various university buildings. Her specialism is an analytical technique called mass spectrometry; used to identify chemical compounds in a substance, its applications include the screening of newborns for rare metabolic disorders and the analysis of whisky to detect barrel contaminants and counterfeits. Milne, for her part, radiates kindly warmth and capable strength; though it is already evident from our phone conversations that, like the retirees in Richard Osman's Thursday Murder Club book series, she is not to be underestimated. It is a little disquieting getting into a car with someone whose sense of smell is so famously acute. Milne, who grew up in Dundee, between the homes of her parents and grandparents, inherited from her grandmother a condition known as hyperosmia, meaning her sense of smell is heightened to the point of being a superpower. While most of us can tell from a sniff of the air that a neighbour has lit a barbecue, she can smell what a passer-by ate for breakfast or tell from a whiff of a book they are carrying what food was in their kitchen last night. As a child, a game of hide and seek was for her an exercise in scent-tracking. Her nose can even tell her when a woman has entered the menopause or if someone is pregnant, 'which can be a bit awkward, though [pregnancy is] a lovely smell, actually'. Ahead of our meeting, Barran has politely warned me to avoid using fragranced products; not just perfume but also scented deodorant or shampoo. Milne dislikes being around synthetic fragrances. Lynx body spray is apparently particularly offensive to her ultra-sensitive olfactory receptors. There was once a bit of an incident when Milne was a guest on 'that TV programme with the red sofa'. The presenter was over-fragranced and she was completely overwhelmed. At the Department of Chemistry, Barran disappears to her lab and I chat with Milne over a coffee. Today she makes accommodations to reduce humanity's assault on her nose, shopping online and avoiding busy spaces. As a school-leaver in the 1960s, though, she opted to train as a nurse, thrusting herself daily into what must surely have been a stinking personal perdition. Milne grins broadly. 'The sluice. The metal bedpans. And yes, it wasn't easy.' Milne doesn't just smell; she trains her sense of smell. As a nurse, she began to build up a medical olfactory library. 'I've always been… we call it nosiness but it's a need for a knowledge of smell. What patients smelt like, that mattered to me. I would know if someone's diabetes was going off. I could tell if someone was struggling post-operatively. The big one was walking into a Nightingale ward with 18 beds on it and smelling tuberculosis. It's not musky like Parkinson's. It's more of an oily biscuit smell. I thought, 'How am I going to deal with this? You can't be here. I've got to sort something out.'' In the past it was considered normal for doctors to use their nose to classify the ailments of a patient. 'Diphtheria smelled sweet, scurvy smelled pungent, typhus smelled like freshly baked rye bread and scrofula, a type of tuberculosis, smelled like stale beer,' writes Jonas Olofsson in The Forgotten Sense: The New Science of Smell. On the battlefields of the First World War, soldiers knew to dread the stench of gas gangrene. Many mothers today probably can't diagnose a specific illness, but say they notice an altered smell in an unwell child. In the modern Western hospital, however, smell is generally overlooked. So Milne used different tactics to deal with the tuberculosis situation. 'There was a very nice consultant and I said to him' – she adopts a gossipy tone – ''Well you should listen to all the things that man's done. He's been all over India…'' Naturally, albeit in a very different way, smell was an important part of Milne's relationship with her husband Les. The two got together at a party when she was 16 'and that was it'. They were both very active: golf, squash and swimming were sports they enjoyed together. Meanwhile, Les went to university, qualified as a medic, and began to train as an anaesthetist. The couple were living in Cheshire and Les was 28 when Milne first noticed something odd. She had always loved her husband's clean, musky smell; it had changed. This time Milne's medical olfactory library failed her. It was another 17 years before Les was diagnosed with Parkinson's, at the age of 45. Still more years after that he and Milne went to a Parkinson's support group and, 'The smell [of the inside of someone's coat as they were taking it off] hit me.' She finally understood. It does not always take a super-smeller to detect the smell of Parkinson's. I have spoken to the friends and relatives of several people with the condition, and many talk about a 'musty' or 'waxy' scent that becomes more pronounced when the person with Parkinson's is under stress. Milne prefers to use the word 'musky', which may seem confusing since she also uses this term to describe Les's original smell but, as she puts it, 'There is a spectrum to musk.' What initially set Joy and Les apart was their medical background – Les, who died in 2015 at the age of 65, 'immediately understood what this could mean'. Also their determination. That first contact with Dr Tilo Kunath, the stem-cell biologist whose Edinburgh talk Joy attended, was not accidental: he had been carefully identified and tracked down. Later, in Barran's lab, Milne's highly selective and sensitive nose became a critical asset. When we think of body odour, we think of sweat. I first encountered Barran in a roomful of perfumers, presenting her findings to members of the International Fragrance Association, and she noted that, when asked to smell themselves, most had stuck their nose in the armpit direction. But that's not where the volatile compounds that carry the odour of Parkinson's are located. They're found in sebum, the oily substance secreted from microscopic glands within hair follicles all over the body, except on the palms of the hands and the soles of the feet. Particularly concentrated around the face, scalp and back, it's sebum that you smell when you put your nose to a baby's head or nuzzle up to a partner's back in bed. 'The initial aim was to find out what Joy was smelling. It was a problem I just had to pick up because it was so extraordinary,' says Barran. Sebum was collected from participants using a simple swab, then Barran used Milne's nose alongside a technique called gas chromatography mass spectrometry (GC-MS) for the analysis. GC-MS separates the compounds in a substance and measures their mass and charge so the molecules, or fragments of molecules, can be identified by cross-comparing with special tables. In this way, Barran's early research identified some of the volatile aroma compounds responsible for the distinctive Parkinson's smell: for instance, octadecanoic acid, methyl ester, which is described in scent libraries as having a 'waxy' odour. But it rapidly became clear that sebum conceals a wealth of useful information that goes far further than smell. 'We found a huge amount about [Parkinson's patients] that we really didn't expect to [find]. We're measuring the disease and the effect of the disease – and the medication in some cases – on the individual. And no one had ever done that before,' says Barran. 'No one had taken this bio-fluid [and analysed it]. Many, many, many diagnostic tests are done with blood, of course. And quite a lot with saliva. People just hadn't realised [sebum] was diagnostically useful.' Her research identifies around 27,000 features in sebum, about 10 per cent of which are different in Parkinson's. 'We haven't found anything that is only present in Parkinson's,' she explains. 'It's about the whole pattern.' From no more than the simple swipe of a swab down someone's back, this has given extraordinary insight into what might be going on inside a Parkinson's patient's body. For instance, the distinctive pattern of features suggests that the so-called carnitine shuttle, responsible for moving long-chain fatty acids into the mitochondrial membranes for energy production, alters in very early-stage Parkinson's, leading to the fatigue experienced by so many people with the disorder. It's from a selection of the up-regulated features – the trick is selecting which ones – that Barran is developing the swab test. When it is ready, the plan is for it to be used not as a stand-alone diagnostic but in conjunction with an assessment by a neurologist. In the longer term, she says, such a test could help cut waiting times for a diagnosis – currently up to two years in some NHS trusts, according to Parkinson's UK. 'GPs are about 50 per cent correct on referral [to a specialist]. At the moment [in studies] our test has an accuracy of 96.7 per cent. What we don't know is what really happens when it goes to real people.' Barran also expects the test to be used as a screening tool to improve wraparound services, by making it possible for those receiving a Parkinson's diagnosis to get the best possible level of support by seeing specialised nurses and consultants 'and someone from Parkinson's UK' at their initial diagnosis appointment. And such a test is likely to improve diagnosis for women, who tend to be diagnosed late, perhaps because many of the symptoms of Parkinson's are similar to menopause symptoms, perhaps because they are less likely to seek help as Parkinson's is still thought of as a condition that primarily affects men, even though 42 out of every 100 people diagnosed are female. The possibilities for the use of sebum as a diagnostic tool could also be far-reaching. Barran has now patented the method – much refined over the course of her research – of sampling sebum and making it amenable for analysis by a mass spectrometer. She has also founded a company, Sebomix Ltd, dedicated to the investigation of sebum as a diagnostic fluid. 'I really think there is an opportunity for it to be used; for instance, I would like to find markers for Parkinson's co-morbidities like cardiovascular disease. But I'm doing Parkinson's first – and after that we will seek to make it into something with a wider use.' Meanwhile Milne, at 75, has never been busier. Besides her ongoing work with Barran, she is an active and energetic advocate for those with Parkinson's. She's also been approached to work on another smell project, this time nothing to do with illness, but one so secretive she can't disclose anything about it. We walk with her to the station to catch her train back to Perth. She can't be late – despite the fact that it's a Friday afternoon, she has another work appointment the next day. This is a woman who never stops. Broaden your horizons with award-winning British journalism. Try The Telegraph free for 1 month with unlimited access to our award-winning website, exclusive app, money-saving offers and more.
Telegraph
20-03-2025
- Health
- Telegraph
The woman who can smell Parkinson's disease
Joy Milne's life has changed immeasurably since the day she ambushed an eminent stem-cell biologist at a talk in Edinburgh, dumbfounding him by asking why smell wasn't used to detect Parkinson's, when she had noticed a distinctive change to the odour of her husband, Les, more than a decade before his diagnosis. For one thing, there's the post: T-shirts – all of them worn so some presumably extremely ripe – from 'Argentina, all over the world', which arrive at the 75-year-old former nurse's cottage in Perth. They're sent by desperate people who've read about Milne's incredible diagnosing nose and want her to have a sniff, to put them out of unhappy limbo. For the record, she no longer opens the packages: 'It would not be ethical.' Then there's the work, which for Milne and her collaborator Professor Perdita Barran has mushroomed in a previously unimaginable number of directions, many of them frontier-smashing. The two have worked together since 2013 when Barran, a chemist now at the University of Manchester, was asked to help with a pilot study to test Milne's claim that she could smell Parkinson's. Milne was asked to sniff and pronounce on a set of T-shirts that had been worn overnight, either by a Parkinson's sufferer or by a control (hence the unusual mailbag). She aced the test, making just one mistake by assigning a control-group shirt to the Parkinson's group. Or, rather, two mistakes: the 12 T-shirts had been cut in half to create a larger dataset and Milne put both halves of this shirt in the Parkinson's group. Nine months later, its wearer reported that they, too, had been diagnosed. Milne hadn't just got every diagnosis correct, she had outperformed the medical establishment. Parkinson's is the fastest-growing neurological disorder in the world, and the second most common neurodegenerative disease after Alzheimer's. It is characterised by the progressive loss of dopamine-producing neurons in a part of the midbrain called the substantia nigra, which is associated with movement and muscle tone. Crucially, however, the disorder is not typically diagnosed until 60 to 80 per cent of those neurons have already been lost. The Michael J Fox Foundation has co-ordinated a multimillion-dollar investment in the search for a biomarker that could indicate the early presence of Parkinson's, in 2023 announcing that a method had been found to detect an abnormal protein in the spinal fluid (which requires a lumbar puncture to test). Thanks to Milne's nose, Barran has been able to analyse many small-molecule markers and she is 'very close' to a simple, non-invasive skin-swab test of clinical utility for a 'timely diagnosis', expected to undergo trials at Manchester's Wythenshawe Hospital later this year. As Barran is all too aware, a 'timely' diagnosis is seen as something of a mixed blessing given the current lack of treatments to slow or stop the progression of the disease. But many sufferers and their relatives (Milne among them) say their lives would have been easier had they understood, sooner, what was happening to them. Further, the identification of a set of biomarkers for early-stage Parkinson's is likely to accelerate and target the treatment options in development. Barran is also about to publish a paper about her work with Dr Claire Guest at Medical Detection Dogs, who trains dogs to detect the olfactory signals of cancer and, now, Parkinson's. 'The best dog, a golden retriever and Labrador cross called Peanut, was about as good as Joy,' says Barran. Guest explains, 'The learnings from the study we hope to apply to artificial intelligence and electronic noses in the future.' Beyond Parkinson's, research that arose with Milne's nose also has implications for the potential identification and treatment of other diseases by bringing into the spotlight a bodily fluid usually overlooked as a diagnostic: sebum. I meet Barran and Milne in the car park of Manchester Piccadilly station on a freezing day in February. Barran is stylish and crisply intelligent, navigating the rush-hour traffic in her canary-yellow car while giving a commentary on the history of various university buildings. Her specialism is an analytical technique called mass spectrometry; used to identify chemical compounds in a substance, its applications include the screening of newborns for rare metabolic disorders and the analysis of whisky to detect barrel contaminants and counterfeits. Milne, for her part, radiates kindly warmth and capable strength; though it is already evident from our phone conversations that, like the retirees in Richard Osman's Thursday Murder Club book series, she is not to be underestimated. It is a little disquieting getting into a car with someone whose sense of smell is so famously acute. Milne, who grew up in Dundee, between the homes of her parents and grandparents, inherited from her grandmother a condition known as hyperosmia, meaning her sense of smell is heightened to the point of being a superpower. While most of us can tell from a sniff of the air that a neighbour has lit a barbecue, she can smell what a passer-by ate for breakfast or tell from a whiff of a book they are carrying what food was in their kitchen last night. As a child, a game of hide and seek was for her an exercise in scent-tracking. Her nose can even tell her when a woman has entered the menopause or if someone is pregnant, 'which can be a bit awkward, though [pregnancy is] a lovely smell, actually'. Ahead of our meeting, Barran has politely warned me to avoid using fragranced products; not just perfume but also scented deodorant or shampoo. Milne dislikes being around synthetic fragrances. Lynx body spray is apparently particularly offensive to her ultra-sensitive olfactory receptors. There was once a bit of an incident when Milne was a guest on 'that TV programme with the red sofa'. The presenter was over-fragranced and she was completely overwhelmed. At the Department of Chemistry, Barran disappears to her lab and I chat with Milne over a coffee. Today she makes accommodations to reduce humanity's assault on her nose, shopping online and avoiding busy spaces. As a school-leaver in the 1960s, though, she opted to train as a nurse, thrusting herself daily into what must surely have been a stinking personal perdition. Milne grins broadly. 'The sluice. The metal bedpans. And yes, it wasn't easy.' Milne doesn't just smell; she trains her sense of smell. As a nurse, she began to build up a medical olfactory library. 'I've always been… we call it nosiness but it's a need for a knowledge of smell. What patients smelt like, that mattered to me. I would know if someone's diabetes was going off. I could tell if someone was struggling post-operatively. The big one was walking into a Nightingale ward with 18 beds on it and smelling tuberculosis. It's not musky like Parkinson's. It's more of an oily biscuit smell. I thought, 'How am I going to deal with this? You can't be here. I've got to sort something out.'' In the past it was considered normal for doctors to use their nose to classify the ailments of a patient. 'Diphtheria smelled sweet, scurvy smelled pungent, typhus smelled like freshly baked rye bread and scrofula, a type of tuberculosis, smelled like stale beer,' writes Jonas Olofsson in The Forgotten Sense: The New Science of Smell. On the battlefields of the First World War, soldiers knew to dread the stench of gas gangrene. Many mothers today probably can't diagnose a specific illness, but say they notice an altered smell in an unwell child. In the modern Western hospital, however, smell is generally overlooked. So Milne used different tactics to deal with the tuberculosis situation. 'There was a very nice consultant and I said to him' – she adopts a gossipy tone – ''Well you should listen to all the things that man's done. He's been all over India…'' Naturally, albeit in a very different way, smell was an important part of Milne's relationship with her husband Les. The two got together at a party when she was 16 'and that was it'. They were both very active: golf, squash and swimming were sports they enjoyed together. Meanwhile, Les went to university, qualified as a medic, and began to train as an anaesthetist. The couple were living in Cheshire and Les was 28 when Milne first noticed something odd. She had always loved her husband's clean, musky smell; it had changed. This time Milne's medical olfactory library failed her. It was another 17 years before Les was diagnosed with Parkinson's, at the age of 45. Still more years after that he and Milne went to a Parkinson's support group and, 'The smell [of the inside of someone's coat as they were taking it off] hit me.' She finally understood. It does not always take a super-smeller to detect the smell of Parkinson's. I have spoken to the friends and relatives of several people with the condition, and many talk about a 'musty' or 'waxy' scent that becomes more pronounced when the person with Parkinson's is under stress. Milne prefers to use the word 'musky', which may seem confusing since she also uses this term to describe Les's original smell but, as she puts it, 'There is a spectrum to musk.' What initially set Joy and Les apart was their medical background – Les, who died in 2015 at the age of 65, 'immediately understood what this could mean'. Also their determination. That first contact with Dr Tilo Kunath, the stem-cell biologist whose Edinburgh talk Joy attended, was not accidental: he had been carefully identified and tracked down. Later, in Barran's lab, Milne's highly selective and sensitive nose became a critical asset. When we think of body odour, we think of sweat. I first encountered Barran in a roomful of perfumers, presenting her findings to members of the International Fragrance Association, and she noted that, when asked to smell themselves, most had stuck their nose in the armpit direction. But that's not where the volatile compounds that carry the odour of Parkinson's are located. They're found in sebum, the oily substance secreted from microscopic glands within hair follicles all over the body, except on the palms of the hands and the soles of the feet. Particularly concentrated around the face, scalp and back, it's sebum that you smell when you put your nose to a baby's head or nuzzle up to a partner's back in bed. 'The initial aim was to find out what Joy was smelling. It was a problem I just had to pick up because it was so extraordinary,' says Barran. Sebum was collected from participants using a simple swab, then Barran used Milne's nose alongside a technique called gas chromatography mass spectrometry (GC-MS) for the analysis. GC-MS separates the compounds in a substance and measures their mass and charge so the molecules, or fragments of molecules, can be identified by cross-comparing with special tables. In this way, Barran's early research identified some of the volatile aroma compounds responsible for the distinctive Parkinson's smell: for instance, octadecanoic acid, methyl ester, which is described in scent libraries as having a 'waxy' odour. But it rapidly became clear that sebum conceals a wealth of useful information that goes far further than smell. 'We found a huge amount about [Parkinson's patients] that we really didn't expect to [find]. We're measuring the disease and the effect of the disease – and the medication in some cases – on the individual. And no one had ever done that before,' says Barran. 'No one had taken this bio-fluid [and analysed it]. Many, many, many diagnostic tests are done with blood, of course. And quite a lot with saliva. People just hadn't realised [sebum] was diagnostically useful.' Her research identifies around 27,000 features in sebum, about 10 per cent of which are different in Parkinson's. 'We haven't found anything that is only present in Parkinson's,' she explains. 'It's about the whole pattern.' From no more than the simple swipe of a swab down someone's back, this has given extraordinary insight into what might be going on inside a Parkinson's patient's body. For instance, the distinctive pattern of features suggests that the so-called carnitine shuttle, responsible for moving long-chain fatty acids into the mitochondrial membranes for energy production, alters in very early-stage Parkinson's, leading to the fatigue experienced by so many people with the disorder. It's from a selection of the up-regulated features – the trick is selecting which ones – that Barran is developing the swab test. When it is ready, the plan is for it to be used not as a stand-alone diagnostic but in conjunction with an assessment by a neurologist. In the longer term, she says, such a test could help cut waiting times for a diagnosis – currently up to two years in some NHS trusts, according to Parkinson's UK. 'GPs are about 50 per cent correct on referral [to a specialist]. At the moment [in studies] our test has an accuracy of 96.7 per cent. What we don't know is what really happens when it goes to real people.' Barran also expects the test to be used as a screening tool to improve wraparound services, by making it possible for those receiving a Parkinson's diagnosis to get the best possible level of support by seeing specialised nurses and consultants 'and someone from Parkinson's UK' at their initial diagnosis appointment. And such a test is likely to improve diagnosis for women, who tend to be diagnosed late, perhaps because many of the symptoms of Parkinson's are similar to menopause symptoms, perhaps because they are less likely to seek help as Parkinson's is still thought of as a condition that primarily affects men, even though 42 out of every 100 people diagnosed are female. The possibilities for the use of sebum as a diagnostic tool could also be far-reaching. Barran has now patented the method – much refined over the course of her research – of sampling sebum and making it amenable for analysis by a mass spectrometer. She has also founded a company, Sebomix Ltd, dedicated to the investigation of sebum as a diagnostic fluid. 'I really think there is an opportunity for it to be used; for instance, I would like to find markers for Parkinson's co-morbidities like cardiovascular disease. But I'm doing Parkinson's first – and after that we will seek to make it into something with a wider use.' Meanwhile Milne, at 75, has never been busier. Besides her ongoing work with Barran, she is an active and energetic advocate for those with Parkinson's. She's also been approached to work on another smell project, this time nothing to do with illness, but one so secretive she can't disclose anything about it. We walk with her to the station to catch her train back to Perth. She can't be late – despite the fact that it's a Friday afternoon, she has another work appointment the next day. This is a woman who never stops.
