Latest news with #JamesRowe
Mint
2 days ago
- Business
- Mint
The Alzheimer's drug pipeline is healthier than you might think
Of all the medical challenges that scientists have faced, Alzheimer's disease, the most common form of dementia, has been one of the trickiest. Between 1995 and 2021 private money spent on Alzheimer's research totalled $42.5bn, but more than 140 trials failed to deliver a single drug capable of slowing the disease. Yet the tide may be turning. There are two working drugs, offering modest benefits, on the market. A new review paper suggests more could soon follow. There are 182 clinical trials for Alzheimer's treatments under way in 2025—an 11% increase on the previous year—testing 138 different drugs, of which 12 are set to complete their final 'phase 3' trials this year. Moreover this pipeline includes medicines aimed at a diverse range of targets in the brain, reflecting an increasingly sophisticated understanding of the molecular processes behind Alzheimer's and dementia more broadly. For decades, the theory that has dominated Alzheimer's research, and drug pipelines, is known as the amyloid hypothesis. It argues that the primary cause of the disease is the accumulation of plaques of beta-amyloid proteins in the brain. These would lead to a cascade of negative effects including neuronal dysfunction, brain-cell death and neuroinflammation. The amyloid hypothesis was supported by genetic evidence, which showed mutations in key genes within families to be linked to early onset of the disease. The success of the two drugs already treating Alzheimer's—lecanemab and donanemab, which arrived on the market in 2023 and 2024, respectively—proves that a connection exists. Both help to clear amyloid from the brain, and offer modest help to a subset of patients for whom the drug is thought to be safe and useful. They slow the progression of the disease by about one-third, according to clinical trials, meaning patients can retain their quality of life for longer. The excitement generated by these drugs was tinged, however, with a feeling that they were not much to show for decades of effort. The singular focus on amyloid was probably misplaced. James Rowe, a professor of cognitive neurology at the University of Cambridge, says that although amyloid accumulation is a critical 'early trigger' for the disease, by the time patients arrive at his clinic there are other neural processes accelerating the illness. These include the accumulation of a misshapen version of a protein called tau; increased metabolic stress on brain cells; neuroinflammation; and degeneration of the brain's blood supply. A more nuanced understanding of Alzheimer's is at last being reflected in drug development. That is the conclusion of Jeffrey Cummings at the University of Nevada, Las Vegas, and colleagues in a review published on June 3rd in the journal Translational Research & Clinical Interventions. Academic experts, and investors, agree. Dame Kate Bingham is the managing partner of SV Health Investors, a venture-capital firm based in London that in 2015 started the first fund dedicated to discovering new treatments for dementia in 2015. At the time the drug pipeline for Alzheimer's was mainly focused on tackling amyloid. She says the growing diversity of potential targets today gives her increased optimism. Fully one-third of the new drugs are repurposed, which means they are already approved for use in other conditions and are being redeployed to Alzheimer's. The appeal of this approach is that the drugs already have known safety and toxicity profiles, and can be approved quickly and developed cheaply. One of the more well-known is semaglutide, a diabetes and weight-loss drug whose anti-inflammatory and metabolic benefits have led to its being tested as a treatment for mild cognitive impairment. The drug piromelatine, meanwhile, works on melatonin and serotonin receptors in the brain, which help regulate sleep. As healthy sleep is thought to increase the rate at which amyloid and other waste proteins are cleared, improving it may slow the progression of Alzheimer's. Then there is AR1001 (also known as mirodenafil), which was originally developed for erectile dysfunction and is being tested for its neuroprotective properties. The drug increases levels of a molecule in the brain called cGMP which, in turn, activates pathways that support the survival of nerve cells and improve connections between brain cells. Drugs in this category are known to improve blood flow, so the drug might also have an impact on the brain's vascular health. Another repurposed drug is nabilone, which interacts with the cannabinoid receptors in the body. (The most well known molecule of this kind is tetrahydrocannabinol, the active compound in cannabis). It was originally developed to treat nausea and vomiting in those undergoing cancer chemotherapy. It is now being tested as a potential treatment for agitation and behavioural problems in those with Alzheimer's. Guanfacine, a drug that improves attention and executive function in those with ADHD, is also being tested to see if it can offer similar benefits. Repurposed drugs do not necessarily have a higher chance of success in late-stage trials than those with a novel mechanism. Dame Kate argues that innovative approaches that use new molecular targets, rather than repurposing, will have the greatest impact on the disease. One area of innovation centres around drugs that can tackle inflammation in the brain. Particular attention is being paid to brain cells called microglia, which play a central role in the brain's immune response and, most probably, its fight against Alzheimer's. Microglia have been described as acting as the brain's fire service, police and binmen, because they respond to emergencies, maintain order and clear up debris. A number of drugs are trying to target the protein TREM2 on the surface of microglia in the hope of boosting their activity. Combinations of drugs are also being tested. For example, it is hoped that a pairing of dasatinib, a cancer drug, and quercetin, a molecule derived from plants, will clear ageing and dysfunctional cells. Drug combinations that target different pathways and components of an illness have made big inroads into other complex and intractable diseases such as cancer and HIV. Some of the errors of the past have been corrected. Dr Rowe says that early attempts to design amyloid-clearing drugs did not remove enough amyloid, or did so too slowly. The patient selection in trials was also poor, with many patients included who—it later turned out—did not have Alzheimer's at all. Today's trials still have blind spots, warns Antonella Santuccione-Chadha, the founder of the Women's Brain Foundation, a non-profit that studies how sex affects brain and mental health. Many still fail to differentiate patients by sex, she says. Yet women are twice as likely to develop Alzheimer's, a difference that cannot be explained solely by their longer lifespans, and the disease seems to progress differently in their brains. At any given stage of the disease, tau proteins spread farther in women than in men, says Dr Chadha. It would help the trials—and patients—if more people were tested for Alzheimer's earlier on, so that they could be enrolled to try the new drugs. A single register of those with the disease would also be useful, making it easier for patients to find trials, and for drug companies to find patients. Much, therefore, remains to be done. But for those suffering from a horrible and as yet insurmountable disease that steals so many minds, there is also some much needed hope.
Hindustan Times
3 days ago
- Business
- Hindustan Times
The Alzheimer's drug pipeline is healthier than you might think
OF ALL THE medical challenges that scientists have faced, Alzheimer's disease, the most common form of dementia, has been one of the trickiest. Between 1995 and 2021 private money spent on Alzheimer's research totalled $42.5bn, but more than 140 trials failed to deliver a single drug capable of slowing the disease. Yet the tide may be turning. There are two working drugs, offering modest benefits, on the market. A new review paper suggests more could soon follow. There are 182 clinical trials for Alzheimer's treatments under way in 2025—an 11% increase on the previous year—testing 138 different drugs, of which 12 are set to complete their final 'phase 3' trials this year. Moreover this pipeline includes medicines aimed at a diverse range of targets in the brain, reflecting an increasingly sophisticated understanding of the molecular processes behind Alzheimer's and dementia more broadly. For decades, the theory that has dominated Alzheimer's research, and drug pipelines, is known as the amyloid hypothesis. It argues that the primary cause of the disease is the accumulation of plaques of beta-amyloid proteins in the brain. These would lead to a cascade of negative effects including neuronal dysfunction, brain-cell death and neuroinflammation. The amyloid hypothesis was supported by genetic evidence, which showed mutations in key genes within families to be linked to early onset of the disease. The success of the two drugs already treating Alzheimer's—lecanemab and donanemab, which arrived on the market in 2023 and 2024, respectively—proves that a connection exists. Both help to clear amyloid from the brain, and offer modest help to a subset of patients for whom the drug is thought to be safe and useful. They slow the progression of the disease by about one-third, according to clinical trials, meaning patients can retain their quality of life for longer. The excitement generated by these drugs was tinged, however, with a feeling that they were not much to show for decades of effort. The singular focus on amyloid was probably misplaced. James Rowe, a professor of cognitive neurology at the University of Cambridge, says that although amyloid accumulation is a critical 'early trigger' for the disease, by the time patients arrive at his clinic there are other neural processes accelerating the illness. These include the accumulation of a misshapen version of a protein called tau; increased metabolic stress on brain cells; neuroinflammation; and degeneration of the brain's blood supply. A more nuanced understanding of Alzheimer's is at last being reflected in drug development. That is the conclusion of Jeffrey Cummings at the University of Nevada, Las Vegas, and colleagues in a review published on June 3rd in the journal Translational Research & Clinical Interventions. Academic experts, and investors, agree. Dame Kate Bingham is the managing partner of SV Health Investors, a venture-capital firm based in London that in 2015 started the first fund dedicated to discovering new treatments for dementia in 2015. At the time the drug pipeline for Alzheimer's was mainly focused on tackling amyloid. She says the growing diversity of potential targets today gives her increased optimism. Fully one-third of the new drugs are repurposed, which means they are already approved for use in other conditions and are being redeployed to Alzheimer's. The appeal of this approach is that the drugs already have known safety and toxicity profiles, and can be approved quickly and developed cheaply. One of the more well-known is semaglutide, a diabetes and weight-loss drug whose anti-inflammatory and metabolic benefits have led to its being tested as a treatment for mild cognitive impairment. The drug piromelatine, meanwhile, works on melatonin and serotonin receptors in the brain, which help regulate sleep. As healthy sleep is thought to increase the rate at which amyloid and other waste proteins are cleared, improving it may slow the progression of Alzheimer's. Then there is AR1001 (also known as mirodenafil), which was originally developed for erectile dysfunction and is being tested for its neuroprotective properties. The drug increases levels of a molecule in the brain called cGMP which, in turn, activates pathways that support the survival of nerve cells and improve connections between brain cells. Drugs in this category are known to improve blood flow, so the drug might also have an impact on the brain's vascular health. Another repurposed drug is nabilone, which interacts with the cannabinoid receptors in the body. (The most well known molecule of this kind is tetrahydrocannabinol, the active compound in cannabis). It was originally developed to treat nausea and vomiting in those undergoing cancer chemotherapy. It is now being tested as a potential treatment for agitation and behavioural problems in those with Alzheimer's. Guanfacine, a drug that improves attention and executive function in those with ADHD, is also being tested to see if it can offer similar benefits. Repurposed drugs do not necessarily have a higher chance of success in late-stage trials than those with a novel mechanism. Dame Kate argues that innovative approaches that use new molecular targets, rather than repurposing, will have the greatest impact on the disease. One area of innovation centres around drugs that can tackle inflammation in the brain. Particular attention is being paid to brain cells called microglia, which play a central role in the brain's immune response and, most probably, its fight against Alzheimer's. Microglia have been described as acting as the brain's fire service, police and binmen, because they respond to emergencies, maintain order and clear up debris. A number of drugs are trying to target the protein TREM2 on the surface of microglia in the hope of boosting their activity. Combinations of drugs are also being tested. For example, it is hoped that a pairing of dasatinib, a cancer drug, and quercetin, a molecule derived from plants, will clear ageing and dysfunctional cells. Drug combinations that target different pathways and components of an illness have made big inroads into other complex and intractable diseases such as cancer and HIV. Some of the errors of the past have been corrected. Dr Rowe says that early attempts to design amyloid-clearing drugs did not remove enough amyloid, or did so too slowly. The patient selection in trials was also poor, with many patients included who—it later turned out—did not have Alzheimer's at all. Today's trials still have blind spots, warns Antonella Santuccione-Chadha, the founder of the Women's Brain Foundation, a non-profit that studies how sex affects brain and mental health. Many still fail to differentiate patients by sex, she says. Yet women are twice as likely to develop Alzheimer's, a difference that cannot be explained solely by their longer lifespans, and the disease seems to progress differently in their brains. At any given stage of the disease, tau proteins spread farther in women than in men, says Dr Chadha. It would help the trials—and patients—if more people were tested for Alzheimer's earlier on, so that they could be enrolled to try the new drugs. A single register of those with the disease would also be useful, making it easier for patients to find trials, and for drug companies to find patients. Much, therefore, remains to be done. But for those suffering from a horrible and as yet insurmountable disease that steals so many minds, there is also some much needed hope. Curious about the world? To enjoy our mind-expanding science coverage, sign up to Simply Science, our weekly subscriber-only newsletter. Get 360° coverage—from daily headlines to 100 year archives.
Western Telegraph
4 days ago
- Business
- Western Telegraph
‘Hope on the horizon' as drugs assessed for Alzheimer's prevention
Some 138 treatments are being assessed in clinical trials. A third of drugs currently being trialled are 'repurposed' medications that are already being used to tackle other diseases, including diabetes, multiple sclerosis and cholesterol, according to the new review. 182 clinical trails are assessing treatments for Alzheimer's disease One such trial is assessing whether semaglutide, the main ingredient for the weight loss and diabetes drug Ozempic and weight loss drug Wegovy, can slow the progression of dementia. And four late-stage trials are looking at preventing disease. Experts said that drugs targeting amyloid protein build up in the brain, such as lecanemab and donanemab, are 'only one part of the overall strategy' as they expressed excitement over the variety of new drugs, which are being tested among patients. The new review of Alzheimer's disease in clinical trials in 2025 found 182 clinical trials assessing the impact of 138 drugs. This latest report shows us that there is hope on the horizon for people with Alzheimer's Dr Sheona Scales The number of trials represents an 11% increase on the previous year, according to the review, which was led by an expert from the University of Nevada in the US and has been published in the journal Alzheimer's and Dementia: Translational Research and Clinical Interventions. Commenting on the paper, Dr Sheona Scales, director of research at Alzheimer's Research UK, said: 'This year has really given us real cause for optimism.' She said that as well as more drugs coming through the pipeline, the treatment targets are 'more diverse' and 'looking at all stages of the disease'. She added: 'What this paper is showing us is that the pipeline of drug development is growing, it's diversifying and accelerating.' 'This latest report shows us that there is hope on the horizon for people with Alzheimer's, building on lecanemab and donanemab.' One of the most exciting things of this report is the number of large scale late-stage trials on prevention Prof James Rowe Dr Emma Mead, chief scientific officer of the Oxford Drug Discovery Institute, added: 'Today we are at a tipping point in dementia research as we understand more and more about the diseases that drive dementia. 'This gives us opportunities to slow and ultimately stop this devastating condition and today's announcement demonstrates that researchers are able to translate these understandings towards potential new treatments.' James Rowe, professor of cognitive neurology at the University of Cambridge and consultant neurologist, said: 'What strikes me is not just the number of new drugs, which is increasing year on year, but their range of targets (and) the range in which they work, giving us multiple shots on goal.' On the drugs which are being investigated for the prevention of disease, Prof Rowe said: 'One of the most exciting things of this report is the number of large-scale late-stage trials on prevention. 'And the aspiration to prevent, not just treat, is starting to be seen in the figures we see in these charts today.' He added: 'One way this can work is you take a treatment that you show to be working in people with symptoms with the illness, and then you simply bring it forward by some years. 'The ones that are in trial at the moment are really… bringing forward an effective treatment to earlier stage.' Being able to repurpose drugs licenced for other health conditions could help to accelerate progress and help to open up other avenues for to prevent or treat dementia causing diseases Dr Emma Mead, chief scientific officer of the Oxford Drug Discovery Institute For instance, people with a genetic risk of Alzheimer's could receive some drugs earlier to see if they protect against the disease. On the repurposing of current drugs, Dr Mead said that it can usually take 10 to 15 years for new drugs to be tested and approved for use. 'Being able to repurpose drugs licensed for other health conditions could help to accelerate progress and help to open up other avenues to prevent or treat dementia causing diseases,' she said. 'A really promising example of this is the drug semaglutide, which is currently being trialled in people with mild cognitive impairment.' Meanwhile, academics said lecanemab and donanemab, which can be used for treating mild cognitive impairment in Alzheimer's patients, are an 'important first step' in the battle against the disease. The treatments were initially approved for UK use by regulators but then deemed not cost-effective for NHS use. The National Institute for Health and Care Excellence (Nice) is taking more evidence on donanemab and lecanemab and is expected to announce its decision in the summer. Dr Scales added: 'Lecanemab and donanemab have represented a huge leap forward in our understanding and ability to be able to treat Alzheimer's disease. 'What they've done is they've proved that we're able to modify the course of Alzheimer's disease, and what that has done is opened up the door to future treatments that we hope are more effective, easier to deliver and and able to deliver for our patients.' She said studies are showing 'even more complexities' around Alzheimer's and that in the future, people may be treated with a combination of drugs, depending on when they are diagnosed and the type of dementia they have. Dr Richard Oakley, associate director of research at Alzheimer's Society, said: 'This paper shows that 2025 is shaping up to be a landmark year for Alzheimer's disease drug development. 'With more trials under way than ever before and more drugs entering the pipeline, there is hope on the horizon for the nearly one million people living with dementia in the UK.'
Yahoo
25-05-2025
- Sport
- Yahoo
'Thank you to the supporters that always stuck with us' - Walker's parting message
Sam Walker has penned an emotional farewell message after confirming his time at King's Lynn Town has officially come to an end. Walker moved to The Walks in September 2023 as assistant manager to Adam Lakeland, who was sacked almost a fortnight ago. The 38-year-old started nine games in the 2024-25 season and joins released pair Jonny Margetts, Josh McCammon and Tommy Hughes as well as Josh Coulson, Greg Taylor and Dylan Crowe through the exit door. More departures, and incomings, are expected soon as new boss James Rowe begins building his own squad. Walker wrote on social media: 'My time at King's Lyn Town has now come to an end after being notified yesterday. 'When Adam and I came into the club we were languishing at the bottom of the league with no direction, no purpose or cohesion on and off the grass. 'During the early months that were extremely challenging, we worked day and night to find solutions that would help extract the maximum from the group we inherited. 'We found a way to do that and steered the club away from relegation and saved them from something everyone thought was inevitable given the circumstances we walked into. 'This season we outlined our plan to get the club promoted, something we addressed to the players on the first day of pre-season. We built a culture and a togetherness that would take us all the way to the play-offs only for it to end in heartbreak. 'To our players, I can't speak highly enough of you all. You trusted is, you let us guide you and you gave us absolutely everything from the first day until our last. I have loved working with you all every day. 'Thank you to the supporters that always stuck with us, especially the tough afternoons and evenings early on. We felt the passion that you all have for our club and it's something we have nothing but admiration for. 'To the chairman, our staff and all the volunteers at the club simply put, the place wouldn't run without you all. You're all so selfless and hardworking. I'll miss seeing you all. 'To the gaffer, thankyou for giving me the responsibility to be an extension of you. Watching you work as hard as you do and to make the sacrifices you've made is nothing short of remarkable. I hope the people associated with King's Lynn know how hard you worked to give them a team they could be proud of.'
BBC News
23-05-2025
- Business
- BBC News
'I'm proud of the badge': King's Lynn Town's new head coach
A football club has made two big announcements - the chairman has stepped down and it has appointed a new head owner Stephen Cleeve is leaving King's Lynn Town FC, who play in National League North, after nine Turn Sports Investments has taken over, and within hours had appointed James Rowe as head said: "I'm sure it's going to be in good hands. I'm sure the club will go forward and it will go on to even greater things." He said his time at the club felt like "being part of a family". Referring to Rowe's appointment, he said: "He's very knowledgeable, very intelligent and he's a winner and he wants to win football matches."I've sold him a couple of players in the past... I'm sure he will do a good job and he's also a local lad who lives in Suffolk." Rowe joins the Linnets after managing Gloucester City, Chesterfield and AFC Fylde. He said he was delighted to be joining the club and his aim was to make it "competitive". "I was proud to put the badge on yesterday... we hope we can inspire people from our performances from game one." He said he wanted to sign-up more local talent. "I'm an all encompassing manager. "I like to recruit the players," said Rowe. Follow Norfolk news on BBC Sounds, Facebook, Instagram and X.
