Published39 minutes agoSharecloseShare pageCopy linkAbout sharingBy James GallagherHealth and science correspondentHow we are born – by Caesarean-section or vaginal delivery – alters how our immune system responds to vaccines, a Scottish and Dutch study suggests. Babies born vaginally had double the level of protective antibodies produced after childhood vaccines.The researchers said the difference was caused by the types of good bacteria, which colonise our bodies at birth.And while C-section babies do get protection, it may need topping up with probiotics or extra vaccines. Our birth is the moment we emerge from the sterile world of the womb to one teeming with microscopic life. Microbes – including bacteria, fungi, viruses and archaea – make our bodies home and eventually outnumber our “human” cells. This hidden half of ourselves is known as the microbiome and one of its roles is training our immune system early in life. Listen to: The Second Genome Podcast exploring our hidden microbial selves on BBC SoundsDoes vaginal seeding boost health?More than half your body is not humanWhy a faecal transplant could save your lifeIf you are born through your mother’s birth canal then the first microbes you encounter are the ones that live in her vagina. A C-section sets you on a different path, as those early colonisers of your body are bugs living on people’s skin or in the hospital or home. The researchers at the University of Edinburgh as well as Spaarne Hospital and Utrecht University Medical Centre in the Netherlands wanted to know what impact this had on vaccines. They tracked the gut microbiomes of 120 babies from their first dark green sticky poo (the meconium) until they were a year old. The results published in the journal Nature Communications showed higher levels of Bifidobacterium and Escherichia coli species (only a few strains of E. coli are dangerous) in the children born vaginally. They said these beneficial bacteria were leading to around double the levels of antibodies in response to the pneumococcal and meningococcal vaccines. Other vaccines including flu and BCG for tuberculosis have already been shown to be influenced by the microbiome.”The initial communication between the immune system and microbes is important,” Prof Debby Bogaert, the chair of paediatric medicine at the University of Edinburgh, told me.She said gut bacteria released chemicals – called short chain fatty acids – that told the immune system it was time to switch on. Without them “you see less B-cell development” which are the cells that produce antibodies. All the babies were healthy and had reached full term so the findings are not affected by other diseases or premature birth. Notably all children did make antibodies after vaccination, so C-section babies are not unprotected. However, the researchers said the findings were particularly important for those with genetic disorders or who are born premature, as their immune systems are already not fully developed. What can be done about it?There is often a medical need for C-sections to protect the health of mother or baby. There has been a recent trend for “vaginal seeding” in which C-section babies are smeared with vaginal fluids from the mother. And a recent study even performed a faecal transplant – or trans-poo-tion- which gives the mother’s gut bacteria to the child. Both aim to replace the missing microbes. However, Prof Bogaert told me: “Theoretically it might be ideal to give missing microbes back to the child born by C-section, but in practice that is quite complicated and you have to make sure it is not dangerous.”The scientific trials screened the faecal matter for any dangerous infections, which is less practical if it has to be done for every C-section baby.Prof Bogaert thinks giving a precise cocktail of beneficial bacteria – a probiotics – to C-section babies would be a “safer route”. Alternatively C-section babies could be given an extra dose of vaccine. Prof Neil Mabbott, an expert in immunology at The Roslin Institute, also University of Edinburgh, said it was uncertain that microbe levels in the body were directly responsible for increased antibody responses.But he added: “This study raises the possibility that it may be possible to treat infants, especially caesarean-delivered infants, with a bacterial supplement or even a product produced by these beneficial bacteria to help improve their immune systems, enhance their responses to certain vaccines and reduce their susceptibility to infections.”Dr George Savva, a statistician at the Quadram Institute Bioscience, said: “This paper is important in beginning to understand the factors that contribute to vaccine response in infants and the role of the microbiome.”But he said it was a relatively small study, and that further research would be needed before it was safe to draw firm conclusions.Follow James on Twitter

Published2 days agoSharecloseShare pageCopy linkAbout sharingImage source, James GallagherBy James GallagherInside Health presenter, BBC Radio 4I hope this vial of blood contains answers because I have a nagging question – have I managed to dodge Covid?It seems remarkable that anyone could. The virus has swept the world since it emerged in China nearly three years ago. Fresh variants have become better and better at infecting us. Even vaccines make Covid milder rather than being an impenetrable shield. Yet I worked in the office throughout, even in lockdowns, and the virus ripped through the rest of my family and I didn’t get sick. And I’m far from the only person to have gone through the pandemic without getting the walloping symptoms of Covid or to have never tested positive. One estimate in the summer suggested around one-in-10 people in the UK still hadn’t been infected. So what’s going on? And does my body – and those of other “never-Coviders” – contain some secret to tackling the disease? There are three broad possibilities if you think you’ve dodged the virus: You’re wrong – you have actually been infected, but never realised You’ve never come into contact with it Or your body has some extra defence that has repelled it”There are a lot of people saying, ‘I’ve never had ‘Covid-the-disease’. Most probably aren’t right, they may have been infected and it just didn’t result in any symptoms,” Dr Lindsay Broadbent, a virologist at the University of Surrey, tells me.”But we do know there are just some people who have never been infected, even in high risk environments such as nurses,” she adds.Listen to Inside Health: Have I dodged Covid?One study of people being regularly tested found half of those catching the Omicron variant remained blissfully unaware or put their mild symptoms down to something else. My blood – painfully milked out of my index finger – will determine whether I have been deluding myself too. I seal the blood in a vial and post it to a research laboratory for analysis of the mixture of antibodies it contains. Antibodies are a part of the immune system. They act like missiles that stick to viruses. This stops them infecting our body’s cells and tells the rest of the immune system to kill the virus. Different antibodies stick to different parts of the virus and the test focuses on two of them:Anti-S antibodies that stick to a protein on the surface of the virus called spikeAnti-N antibodies that stick to an inner layer of the virus – called the nucleocapsid – that protects the virus’s genetic codeAll the vaccines used in the UK train the body to attack only the spike protein. Even a year after my last booster, the test shows I have high levels of anti-S antibodies.Your body learns to attack the other parts of the virus only when facing the virus itself. If anti-N antibodies were in my blood that would mean I’d been infected with Covid.I test negative and the idea I have dodged Covid passes its first hurdle. Prof Mala Maini, a professor of viral immunology, invites me into her laboratory at University College London to explore the results. “It could mean that you’ve never had the infection, but it could also mean you’ve made anti-N antibodies and they’ve gone from your blood,” she tells me.Image source, James GallagherHowever, I have never tested positive despite:Testing with lateral flows twice a week for a chunk of the pandemic to come into the officeDriving to a grim car park for a PCR test or taking a lateral flow whenever I had symptoms Testing daily when family were sick with CovidProf Maini concludes: “Put together with your negative anti-N antibody test, it suggests you may be someone who has escaped a full-blown infection. “You may have had what we call an ‘abortive’ infection.”An immunological head startThe idea of an abortive infection is you are exposed to the virus, it even gets into the right places to start an infection, but the body gets on top of it before it takes off. We know this happens from studies that have tried to deliberately infect people with Covid. These human challenge trials squirted virus up the nose of healthy volunteers, but in the first 34 people to take part, only half actually developed an infection. The first line of protection is the innate immune system. This is our body’s default defence. It cannot learn or “remember” infections, so each time is like the first time. But it is so fast it can stop an infection in its tracks. Dr Broadbent demonstrated this by conducting experiments using miniature lungs grown from people’s cells – called organoids – and trying to infect them with the virus.”We found one person that we just could not infect, we were sticking bucketloads of virus on these cells and there was no infection,” she tells me.The other half of the immune system is known as the adaptive immune system, which learns and gets better with practice. This is how vaccines prepare the body for fighting Covid. “It could just be that the vaccines worked well for you and have given you very good protection,” suggests Prof Maini.But vaccines seem to give only limited and rapidly-waning protection against catching the virus. And there were no vaccines for the first year of the pandemic. However, there are other ways this part of the immune system could stop an infection.Blood and lung samples taken from hospital staff before the pandemic, showed some already had protective T-cells. These are like sentinels that inspect other cells for signs of infection. If they find a contaminated cell, they kill it. Even before the first cases arrived in the UK, some people had these anti-Covid soldiers in their bodies. They are probably the result of catching other common cold coronaviruses, which are closely related to the Covid virus. “If you have young children at school, it’s very likely that you would have been exposed to these in the preceding years,” Prof Maini tells me. “If you’ve got these pre-existing T-cells ready and waiting then they can act much more quickly and bring down the infection before it becomes positive on your test,” she adds.Covid-resistant people inspire new vaccine tacticThe hope is a new generation of vaccines can be developed that mimic this pre-existing immunity. “If you could make T-cells against the inner regions of the virus and get those responses in the nose, airways and lungs there’s a much better chance they could abort the infection before it takes off, that’s the goal,” says Prof Maini. My gut feeling is that the torrent of bugs every toddler brings home from nursery to plague their already weary parents helped me dodge Covid. Other explanations?There are two other possibilities, but they either don’t apply to me or are incredibly rare. Some people have never been exposed to the virus because they have shunned contact with other people. I’ve interviewed the super-shielders who have isolated themselves for nearly 1,000 days, often because they have weakened immune systems that leave them more vulnerable. This isn’t me after getting the train to work throughout and even sharing a bed with a sickly toddler. Podcast: 950 days of shieldingThe other idea is genetic invulnerability, which does happen with other diseases. The famous example is human immunodeficiency virus (HIV). A rare few are born with a lucky genetic mutation that completely shields them from the virus. A mutation in a section of their genetic code – called CCR5 – changes the locks on our body’s cells so HIV can’t get inside. This has been used to cure some people of HIV and similar mutations have been shown to lock coronavirus out of people’s cells.”It’s incredibly, incredibly small numbers that have some kind of genetic resistance,” says Dr Broadbent.So am I safe this winter? So for any of us that have still not caught the virus, can we go into the festive season with confidence or are we actually the most at-risk?The protection from the vaccine means that the chances of being severely ill are greatly lowered even if it cannot stop the infection. But research, including a study in Switzerland, suggests having had the virus and the vaccine – known as hybrid immunity – gives the strongest immune response. “So it may mean that you are a bit more at risk,” warns Prof Maini.Dr Broadbent agrees: “If you don’t think you’ve had it up to now, it does not mean resistance… chances are you’re lucky.”Personally, I suspect writing this piece has tempted fate therefore ensuring I catch Covid by Christmas! Follow James on Twitter, Inside Health was produced by Beth Eastwood.More from Inside HealthMultiple sclerosis: Is a virus we all have causing MS?Long Covid: ‘I’ve had long Covid for two years now’Sickle cell: ‘The revolutionary gene-editing treatment that gave me new life’Cervical cancer: Vaccines could mean only one smear test a lifetimeAnimals for organs: Are pigs the future of organ transplants?Asthma: Why switching inhaler could be better for you and the planetVegan ready meals: How healthy are they?

Published10 minutes agoSharecloseShare pageCopy linkAbout sharingImage source, Getty ImagesBy James GallagherHealth and science correspondentPeople with untreatable cancers have had their immune system redesigned to attack their own tumours.The experimental study involved only 16 patients, but has been called a “leap forward” and a “powerful” demonstration of the potential of such technology.Each person had a treatment developed just for them, which targeted the specific weak spots in their tumour. It is too early to fully assess the therapy’s effectiveness and is expensive and time-consuming. The work focuses on a part of the immune system called T-cells, which patrol the body and inspect other cells for problems. They use proteins – called receptors – to effectively sniff out signs of infection or deviant cells that have become cancerous. Cancers can be tricky for T-cells to spot. A virus is distinctly different to the human body, but cancers are more subtle because they are a corrupted version of our own cells. The idea of the therapy is to boost levels of these cancer-spotting T-cells. It has to be tailored to each patient as each tumour is unique. This is how it works:The researchers scoured patient’s blood for rare T-cells that already had receptors which could sniff out their cancerThey then harvested other T-cells that could not find the cancer and redesigned themTheir original receptors, which may find other problems or infections, were replaced with those from the cancer-searching T-cells Finally, these modified T-cells were then put back into the patient to seek out the tumourTransforming T-cells into a form that can hunt cancer requires considerable genetic manipulation to both remove the genetic instructions for building their old receptors, and give them the instructions for the new ones. It was made possible by tremendous advances in the gene-editing technology Crispr, which acts like a pair of molecular scissors – allowing scientists to easily manipulate DNA. The researchers who developed Crispr won the Nobel Prize for Chemistry in 2020.Image source, Getty ImagesThe trial involved people with colon, breast or lung cancers that had failed to respond to other treatments. The study was designed to test the safety and feasibility of the technology, and showed the modified cells were finding their way into the tumour. The disease continued to get worse in 11 patients, but stabilised in the other five. However, it will take larger studies to work out the correct dose and how effective it really is.”This is a leap forward in developing a personalised treatment for cancer,” said Dr Antoni Ribas, one of the researchers at the University of California, Los Angeles, who tested the approach developed by the company Pact Pharma.The results were presented at a meeting of the Society for Immunotherapy of Cancer and published simultaneously in the journal Nature.Dr Manel Juan, head of the immunology service at Clinic Hospital in Barcelona, said it was “extraordinary work” and “undoubtedly one of the most advanced in the field”.He added: “It opens the door to using this personalised [approach] in many types of cancer and potentially in many other diseases.”‘Designer cells’ reverse one-year-old’s cancerDawn of gene editing medicine?Prof Waseem Qasim, who has given life-saving designer immune systems at Great Ormond Street Hospital, said it was a “powerful early demonstration of what might be possible with newer techniques”.Dr Astero Klampatsa, from the Institute of Cancer Research, London, said the study was “important” but warned that the “time, labour and expense involved” were “huge”.Follow James on Twitter

Published1 day agoSharecloseShare pageCopy linkAbout sharingImage source, NHSBTBy James GallagherHealth and science correspondentBlood that has been grown in a laboratory has been put into people in a world-first clinical trial, UK researchers say. Tiny amounts – equivalent to a couple of spoonfuls – are being tested to see how it performs inside the body. The bulk of blood transfusions will always rely on people regularly rolling up their sleeve to donate.But the ultimate goal is to manufacture vital, but ultra-rare, blood groups that are hard to get hold of.These are necessary for people who depend on regular blood transfusions for conditions such as sickle cell anaemia. If the blood is not a precise match then the body starts to reject it and the treatment fails. This level of tissue-matching goes beyond the well-known A, B, AB and O blood groups. Prof Ashley Toye, from the University of Bristol, said some groups were “really, really rare” and there “might only be 10 people in the country” able to donate. At the moment, there are only three units of the “Bombay” blood group – first identified in India – in stock across the whole of the UK. Podcast: Inside Health on rare blood groupsSickle cell: ‘The revolutionary gene-editing treatment that gave me new life’Image source, NHSBTSo how is the blood grown?The research project combines teams in Bristol, Cambridge, London and at NHS Blood and Transplant. It focuses on the red blood cells that carry oxygen from the lungs to the rest of the body. This is how it works:They start with a normal donation of a pint of blood (around 470ml)Magnetic beads are used to fish out flexible stem cells that are capable of becoming a red blood cellThese stem cells are encouraged to grow in large numbers in the labs And are then guided to become red blood cellsThe process takes about three weeks and an initial pool of around half a million stem cells results in 50 billion red blood cells. These are filtered down to get around 15 billion red blood cells that are at the right stage of development to transplant. “We want to make as much blood as possible in the future, so the vision in my head is a room full of machines producing it continually from a normal blood donation,” Prof Toye told me.Image source, NHSBTThe first two people have taken part in the trial, which aims to test the blood in at least 10 healthy volunteers. They will get two donations of 5-10mls at least four months apart – one of normal blood and one of lab-grown blood. The blood has been tagged with a radioactive substance, often used in medical procedures, so scientists can see how long it lasts in the body. It is hoped the lab-grown blood will be more potent than normal.Red blood cells normally last for around 120 days before they need to be replaced. A typical blood donation contains a mix of young and old red blood cells, whereas the lab-grown blood is all freshly made so should last the full 120 days. The researchers suspect this could allow both smaller and less frequent donations in the future.However, there are considerable financial and technological challenges.The average blood donation costs the NHS around £130. Growing blood will cost vastly more, although the team will not say how much. Another challenge is the harvested stem cells eventually exhaust themselves, which limits the amount of blood that be grown. It will take more research to produce the volumes that would be needed clinically. Discovery enables ‘mass produced blood’Dr Farrukh Shah, the medical director of transfusion at NHS Blood and Transplant, said: “This world-leading research lays the groundwork for the manufacture of red blood cells that can safely be used to transfuse people with disorders like sickle cell.”The potential for this work to benefit hard to transfuse patients is very significant.”Follow James on Twitter More on this story‘I feel reborn after pioneering gene-editing treatment’20 February

Published8 hours agoSharecloseShare pageCopy linkAbout sharingImage source, Museum of LondonBy James GallagherHealth and science correspondentThe devastation of the plague pandemic left such an incredible genetic mark on humanity that it’s still affecting our health nearly 700 years later.Up to half of people died when the Black Death swept through Europe in the mid-1300s.A pioneering study analysing the DNA of centuries-old skeletons found mutations that helped people survive the plague. But those same mutations are linked to auto-immune diseases afflicting people today. The Black Death is one of the most significant, deadliest and bleakest moments in human history. It is estimated that up to 200 million people died.Researchers suspected an event of such enormity must have shaped human evolution. They analysed DNA taken from the teeth of 206 ancient skeletons and were able to precisely date the human remains to before, during or after the Black Death. The analysis included bones from the East Smithfield plague pits which were used for mass burials in London with more samples coming from Denmark. Image source, McMaster UniversityThe standout finding, published in the journal Nature, surrounded mutations in a gene called ERAP2. If you had the right mutations you were 40% more likely to survive the plague. “That’s huge, it’s a huge effect, it’s a surprise to find something like that in the human genome,” Professor Luis Barreiro, from the University of Chicago, told me. The gene’s job is to make the proteins that chop up invading microbes and show the fragments to the immune system, priming it more effectively to recognise and neutralise the foe. The gene comes in different versions – those that work well and those that do nothing – and you get a copy from each parent. So the lucky ones, who were most likely to survive, inherited a high-functioning version from mum and dad. And the survivors had children and so passed those helpful mutations on so they suddenly became much more common. “It’s huge we see a 10% shift over two to three generations, it’s the strongest selection event in humans to date,” evolutionary geneticist Professor Hendrik Poinar, from McMaster University, told me.The results were confirmed in modern day experiments using the plague bacterium – Yersinia pestis. Samples of blood from people with the helpful mutations were more able to resist the infection than those without. “It’s like watching the Black Death unfold in a petri-dish – that’s eye-opening,” said Prof Poinar.Image source, University of ChicagoEven today those plague-resisting mutations are more common than they were before the Black Death. The problem is they have been linked to auto-immune diseases such as the inflammatory bowel disease Crohn’s – what helped keep your ancestors alive 700 years ago but could be damaging your health today. Other historic forces on our DNA have a legacy we feel. Around 1-4% of modern human DNA comes from our ancestors sleeping with Neanderthals and this inheritance affects our ability to respond to diseases including Covid. “So those scars from the past still impact our susceptibility to disease today, in a quite remarkable way,” said Prof Barreiro.Nobel Prize goes to Svante Paabo for Neanderthal workProf Barreiro said the 40% survival advantage was the “strongest selective fitness effect ever estimated in humans”. It seemingly dwarfs the benefit of HIV-resistance mutations or those that help digest milk – although he warns direct comparisons are tricky. The Covid pandemic will not leave a similar legacy though. Evolution works through your ability to reproduce and pass on your genes. Covid largely kills the elderly who have already passed the point of having children. It was plague’s ability to kill across the age spectrum and in such great numbers that meant it had such a lasting impact. Follow James on Twitter More on this storyPlague traced back to Bronze Age23 October 2015Black Death ‘spread by humans not rats’15 January 2018

Published14 minutes agoSharecloseShare pageCopy linkAbout sharingThe Nobel Prize in Physiology or Medicine has gone to Sweden’s Svante Paabo for his work on human evolution. The Prize committee said he achieved the seemingly impossible task of cracking the genetic code of one of our extinct relatives – Neanderthals.He also performed the “sensational” feat of discovering the previously unknown relative – Denisovans.His work helped explore our own evolutionary history and how humans spread around the planet. The Swedish geneticist’s work gets to the heart of some of the most fundamental questions – where do we come from and what allowed us, Homo sapiens, to succeed while our relatives went extinct. Say good morning to our new medicine laureate Svante Pääbo! Pääbo received the news while enjoying a cup of coffee. After the shock wore off, one of the first things he wondered was if he could share the news with his wife, Linda. Photo: Linda Vigilant pic.twitter.com/l27hnzojaL— The Nobel Prize (@NobelPrize) October 3, 2022
The BBC is not responsible for the content of external sites.View original tweet on TwitterIn the 1990s, research on working out the human genetic code was taking place at pace. But that relied on fresh samples of pristine DNA.Prof Paabo’s interest was in the old and degraded genetic material from our ancestors. Many thought it was an impossible challenge. But he was, for the first time, able to sequence DNA from a 40,000-year-old piece of bone.Those results showed that Neanderthals – who mostly lived in Europe and Western Asia – were distinct from both modern day humans and chimpanzees.His work focused on hominins – the group of modern humans that includes us, Homo sapiens, but also our extinct relatives. “By revealing genetic differences that distinguish all living humans from extinct hominins, his discoveries provide the basis for exploring what makes us uniquely human”, the Nobel committee said.Further comparisons between Neanderthal DNA and humans from around the world showed their DNA was a closer matcher to humans coming from Europe or Asia. This tells us that Homo sapiens had sex and children with Neanderthals after migrating out of Africa around 70,000 years ago. And you can still see the legacy of that today. Between 1-4% of modern human DNA comes from our Neanderthal relatives and this even affects our body’s ability to respond to infection.Cave fingerThe next seismic contribution to human origins came in 2008. Scientists had found a 40,000-year-old finger bone in the Denisova cave, in Siberia.Prof Paabo was able to sequence a sample of DNA and the results showed it was a previously unknown hominin – known as Denisovans. And it turned out Homo sapiens bred with these Denisovans too. In parts of South East Asia up to 6% of people’s DNA is Denisovan.Prof Paabo only heard the news this morning when he was called by Thomas Perlmann, the secretary for the Nobel Committee for Physiology or Medicine.”He was overwhelmed, he was speechless. Very happy,” said Prof Perlmann.He wins the 10m Swedish kronor (£800,000) prize.Follow James on TwitterPrevious winners2021 – David Julius and Ardem Patapoutian for their work on how the body senses touch and temperature. 2020 – Michael Houghton, Harvey Alter and Charles Rice for the discovery of the virus Hepatitis C.2019 – Sir Peter Ratcliffe, William Kaelin and Gregg Semenza for discovered how cells sense and adapt to oxygen levels2018 – James P Allison and Tasuku Honjo for discovering how to fight cancer using the body’s immune system2017- Jeffrey Hall, Michael Rosbash and Michael Young for unravelling how bodies keep a circadian rhythm or body clock2016 – Yoshinori Ohsumi for discovering how cells remain healthy by recycling waste2015 – William C Campbell, Satoshi Ōmura and Youyou Tu for anti-parasite drug discoveriesMore on this storyNeanderthal extinction not caused by brutal wipe out9 FebruaryRelated Internet LinksNobel PrizeThe BBC is not responsible for the content of external sites.

Published21 hours agoSharecloseShare pageCopy linkAbout sharingImage source, Getty ImagesTrial results of a drug appearing to slow Alzheimer’s disease represent a “historic moment”, experts say.Pharmaceutical companies Eisai and Biogen have said their drug works when given in the early stages of the disease. The full details have yet to published, but it appears to slow the pace of the brain’s decline.And even the limited data has generated excitement among dementia scientists and charities. Mental agilityThe drug, lecanemab, is designed to remove clumps of toxic beta-amyloid proteins that build up in the brains of people with Alzheimer’s disease. Dozens of other drug trials have failed, leading to questions about whether amyloid was really causing the disease. In this trial, 1,795 volunteers in the early stages of Alzheimer’s disease were injected with lecanemab every two weeks and regularly had their memory and mental agility tested. The pace of cognitive decline had been reduced by 27% over the course of the 18-month trial, compared with people given a dummy, or placebo, treatment, the pharmaceutical companies said.They also showed levels of the toxic protein were lowered in the brain. Side-effects included brain swelling and headaches. The drug will not work for other forms of dementia. ‘Truly encouraging’Biogen chief executive Michel Vounatsos said: “Today’s announcement gives patients and their families hope that lecanemab, if approved, can potentially slow the progression of Alzheimer’s disease and provide a clinically meaningful impact on cognition and function.”The companies are now applying for regulatory approval for the drug to be given in the US, Europe and Japan. Alzheimer’s Research UK research director Dr Susan Kohlhaas said it was a “breakthrough” and a “historic moment for dementia research” as it was the first large clinical trial “in a generation to successfully slow cognitive decline”.Prof John Hardy, from University College London, said the results were “truly encouraging” and “look like the first truly positive mechanistic trial results in Alzheimer’s disease”. “The results look modest but real,” he said.”This is clearly not a magic bullet but it looks like a definite ‘end of the beginning’.”‘Positive result’The same companies previously announced a much hyped Alzheimer’s drug called aducanumab. But its US launch was widely criticised and the EU refused to allow it over doubts about whether it worked. The early data for their latest drug appears clearer, but the full details are not expected to be announced until November. Prof Rob Howard, professor of old-age psychiatry, at UCL, said: “This is an unambiguously statistically positive result and represents something of an historic moment, when we see the first convincing modification of Alzheimer’s disease. “God knows, we’ve waited long enough for this.” Follow James on Twitter.More on this storyAlzheimer’s research takes ‘leap forward’4 AprilBrain stimulation boosts memory for a month22 AugustControversial Alzheimer’s drug rejected by EU17 December 2021US approves first new Alzheimer’s drug in 20 years7 June 2021

Published15 hours agoSharecloseShare pageCopy linkAbout sharingThis video can not be playedTo play this video you need to enable JavaScript in your browser.Scientists say they have slowed and even reversed some of the devastating and relentless decline caused by motor-neurone disease (MND). The treatment works in only 2% of patients but has been described as “truly remarkable” and a “real moment of hope” for the whole disease. One leading expert said it was the first time she had seen patients improve – but this is not a cure. The MND Association said there was “mounting confidence” in the therapy. MND, also known as amyotrophic-lateral sclerosis (ALS), is caused by the death of the nerves that carry messages from the brain to people’s muscles. It affects their ability to move, talk and even breathe. The disease dramatically shortens people’s lives and most die within two years of being diagnosed.Image source, University of SheffieldLes Wood, 68, from South Yorkshire, was the first British patient in the international trial, published in the New England Journal of Medicine.MND had forced him, an electrician, and his wife, Val, a nurse, to give up their careers, as walking and using his hands became more difficult. A mutation in a specific part of his genetic code leads to the production of a toxic form of the protein SOD1, which kills motor neurones. These mutations cause about 2% of MND cases but one in five of those that run in families. The trial on 108 people, funded by pharmaceutical company Biogen, used an innovative type of medicine called gene silencing. The drug tofersen effectively mutes the defective DNA so less SOD1 is produced.Podcast: The Silence of the GenesGene silencing medicine transforms crippling painThe treatment requires monthly lumbar punctures, in which a needle is passed between the bones in the spine to put the drug directly into the spinal fluid. After six months of therapy, those getting the drug had lower levels of SOD1 but were physically no better. After a year, however, it was slowing the pace of the disease – and some patients’ symptoms improved.Les had his first dose in 2016 – and in home videos recorded a year later, he said: “I could genuinely say, hand-on-heart, I felt better.”I actually walked in the house, without sticks, I thought, ‘This drug’s working.'”Now, he says: “MND is a progressive disease – so although my symptoms have continued to worsen, I would not be without the drug and the difference I know it has made to my quality of life.”Image source, University of SheffieldFor Prof Dame Pamela Shaw, the director of the Neuroscience Institute, in Sheffield, and a veteran of more than 25 clinical trials in the disease, this was something incredible. She told me: “This is the first where patients participating have reported improvement in their motor function – ‘I can walk without my sticks. I can go up my garden steps, which I haven’t been able to do for two years. I can write my Christmas cards this year, which I couldn’t do last year.'”The results were a “real moment of hope” and the start of a “new era” in which we can expect progress in other forms of MND too.In the early stages, the researchers say, the drug is stopping further damage. It cannot lead to the formation of new motor neurones and the remaining ones may be taking a year to recover and form new connections with muscle tissue.”It may take time for people to heal from the damage that has already been caused,” said Dr Timothy Miller, the principal investigator, at Washington University.”The vast majority of people living with ALS experience a relentlessly progressive downhill course, so the stabilisation of function is truly remarkable.”Image source, Getty ImagesThe treatment directly targets the fundamental cause of this type of MND so it will do nothing for the 98% of patients without the SOD1 mutation – although, it is hoped the other mutations, in more than 30 different genes, implicated could be targeted in a similar way. “The approach used, of reducing proteins harmful in MND, is likely to have wider applications for more common types of MND,” said Prof Chris McDermott, of University of Sheffield.Tofersen is being considered for regulatory approval in the US and provided free in the UK ahead of a decision on whether the NHS should pay for it.MND Association research director Dr Brian Dickie said the treatment had the “potential to deliver a significant benefit” for a relatively rare group of people with the disease. The big question, he added, was whether to give the drug in the earliest stages of the disease, when it “may be even more effective”, or even to healthy people with the SOD1 mutation to “prevent the onset of disease”.Follow James on Twitter.More on this storyWorkouts increase motor neurone risk – scientists11 June 2021The woman with MND who has had two children3 May

Published2 days agoSharecloseShare pageCopy linkAbout sharingImage source, Getty ImagesResearchers say they have cracked how air pollution leads to cancer, in a discovery that completely transforms our understanding of how tumours arise. The team at the Francis Crick Institute in London showed that rather than causing damage, air pollution was waking up old damaged cells.One of the world’s leading experts, Prof Charles Swanton, said the breakthrough marked a “new era”.And it may now be possible to develop drugs that stop cancers forming. The findings could explain how hundreds of cancer-causing substances act on the body.The classical view of cancer starts with a healthy cell. It acquires more and more mutations in its genetic code, or DNA, until it reaches a tipping point. Then it becomes a cancer and grows uncontrollably. But there are problems with this idea: cancerous mutations are found in seemingly healthy tissue, and many substances known to cause cancer – including air pollution – don’t seem to damage people’s DNA.So what is going on?The researchers who also work at University College London, have produced evidence of a different idea. The damage is already there in our cell’s DNA, picked up as we grow and age, but something needs to pull the trigger that actually makes it cancerous. The discovery came from exploring why non-smokers get lung cancer. The overwhelming majority of lung cancers are caused by smoking but still, one in 10 cases in the UK is down to air pollution.The Crick scientists focused on a form of pollution called particulate matter 2.5 (known as PM2.5), which is far smaller than the diameter of a human hair. Through a series of detailed human and animal experiments they showed:Places with higher levels of air pollution had more lung cancers not caused by smokingBreathing in PM2.5 leads to the release of a chemical alarm – interleukin-1-beta – in the lungsThis causes inflammation and activates cells in the lungs to help repair any damageBut around one in every 600,000 cells in the lungs of a 50-year-old already contains potentially cancerous mutationsThese are acquired as we age but appear completely healthy until they are activated by the chemical alarm and become cancerousCrucially, the researchers were able to stop cancers forming in mice exposed to air pollution by using a drug that blocks the alarm signal. The results are a double breakthrough, both for understanding the impact of air pollution and the fundamentals of how we get cancer. Dr Emilia Lim, one of the Crick researchers, said people who had never smoked but developed lung cancer often had no idea why. “To give them some clues about how this might work is really, really important,” she said.”It’s super-important – 99% of people in the world live in places where air pollution exceeds the WHO guidelines so it really impacts all of us.”Image source, Getty ImagesRethinking cancerBut the results also showed mutations alone are not always enough to cause cancer. It can need an extra element. Prof Swanton said this was the most exciting finding his lab had come across, as it “actually rethinks our understanding of how tumours are initiated”. He said it would lead to a “new era” of molecular cancer prevention.The idea of taking a cancer-blocking pill if you live in a heavily polluted area is not completely fanciful. Doctors have already trialled an interleukin-1-beta drug in cardiovascular disease and found, by complete accident, they cut the risk of lung cancer. The latest findings are being presented to scientists at a conference of the European Society for Medical Oncology.Speaking to the BBC from the conference, Prof Swanton said: “Pollution is a lovely example, but there are going to be 200 other examples of this over the next 10 years.”And he said we needed to rethink how even smoking causes cancer – is it just the known DNA damage caused by the chemicals in tobacco or is the smoke causing inflammation, too?Curiously, the idea that mutated DNA is not enough and cancers need another trigger to grow was first proposed by scientist Isaac Berenblum in 1947.”Philosophically, it’s fascinating. These incredible biologists have done this work 75 years ago and it’s largely been ignored,” said Dr Lim.Michelle Mitchell, chief executive of Cancer Research UK, stressed that “smoking remains the biggest cause of lung cancer”.But she added: “Science, which takes years of painstaking work, is changing our thinking around how cancer develops. We now have a much better understanding of the driving forces behind lung cancer.”Follow James on Twitter.

Published10 hours agoSharecloseShare pageCopy linkAbout sharingImage source, Katie EwerA malaria vaccine with “world-changing” potential has been developed by scientists at the University of Oxford. The team expect it to be rolled out next year after trials showed up to 80% protection against the deadly disease.Crucially, say the scientists, their vaccine is cheap and they already have a deal to manufacture more than 100 million doses a year. The charity Malaria No More said recent progress meant children dying from malaria could end “in our lifetimes”.It has taken more than a century to develop effective vaccines as the malaria parasite, which is spread by mosquitoes, is spectacularly complex and elusive. It is a constantly moving target, shifting forms inside the body, which make it hard to immunise against.Last year, the World Health Organization gave the historic go-ahead for the first vaccine – developed by pharmaceutical giant GSK – to be used in Africa. However, the Oxford team claim their approach is more effective and can be manufactured on a far greater scale. Trial results from 409 children in Nanoro, Burkina Faso, have been published in the Lancet Infectious Diseases. It shows three initial doses followed by a booster a year later gives up to 80% protection. Image source, Katie Ewer”We think these data are the best data yet in the field with any malaria vaccine,” said Prof Adrian Hill, director of the Jenner Institute at the university.The team will start the process of getting their vaccine approved in the next few weeks, but a final decision will hinge on the results of a larger trial of 4,800 children due before the end of the year.The world’s largest vaccine manufacturer – the Serum Institute of India – is already lined up to make more than 100 million doses a year. Prof Hill said the vaccine – called R21 – could be made for “a few dollars” and “we really could be looking at a very substantial reduction in that horrendous burden of malaria”.He added: “We hope that this will be deployed and available and saving lives, certainly by the end of next year.” Malaria has been one of the biggest scourges on humanity for millennia and mostly kills babies and infants. The disease still kills more than 400,000 people a year even after dramatic progress with bed nets, insecticides and drugs.This malaria vaccine is the 14th that Prof Katie Ewer has worked on at Oxford as “this is not like Covid where we have seven vaccines straight away that will work… it’s much, much harder”.She told the BBC it was “incredibly gratifying” to get this far and “the potential achievement that this vaccine could have if it’s rolled out could be really world-changing”. Why so effective?The currently approved vaccine – made by GSK – shares similarities with the one developed in Oxford. Both target the first stage of the parasite’s lifecycle by intercepting it before it gets to the liver and establishes a foothold in the body.The vaccines are built using a combination of proteins from the malaria parasite and the hepatitis B virus, but Oxford’s version has a higher proportion of malaria proteins. The team think this helps the immune system to focus on malaria rather than the hepatitis. The success of the GSK vaccine has partly paved the way for Oxford to be optimistic of having their vaccine out next year – such as by assessing how feasible a vaccination programme in Africa would be.It is hard to give a direct comparison of the two vaccines. GSK’s has gone through large real world trials whereas Oxford’s data may appear more effective due to being given just ahead of the peak malaria season in Burkina Faso. Prof Azra Ghani, chair in infectious disease epidemiology at Imperial College London, said the trial results were “very welcome”, but warned it would take money to get vaccines in arms. “Without this investment, we risk losing the gains that have been made over the last decades and witnessing a rising tide of malaria resurgence,” Prof Ghani said. Gareth Jenkins, from the charity Malaria No More UK said: “Today’s R21 vaccine results from Oxford’s renowned Jenner Institute are another encouraging signal that, with the right support, the world could end child deaths from malaria in our lifetimes.”Follow James on Twitter.More on this storyHistoric go-ahead for malaria vaccine in Africa6 October 2021