ST. LOUIS (Reuters) – Missouri’s only abortion clinic will stay open at least a few more days after a judge on Friday granted a request by Planned Parenthood for a temporary restraining order, allowing the facility to keep operating until a hearing on Tuesday.
Pro-Choice and Pro-Life protesters stand outside of Planned Parenthood as a deadline looms to renew the license of Missouri’s sole remaining Planned Parenthood clinic in St. Louis, Missouri, U.S. May 31, 2019. REUTERS/Lawrence Bryant
Planned Parenthood sued Missouri this week after state health officials said the license for Reproductive Health Services of Planned Parenthood in St. Louis was in jeopardy, meaning the clinic could have closed at midnight unless the judge granted the request for a temporary restraining order.
“Today is a victory for women across Missouri, but this fight is far from over,” Planned Parenthood President Leana Wen said in a statement after Circuit Court Judge Michael Stelzer agreed to the organization’s request.
Representatives for the Missouri Department of Health and Senior Services could not be immediately reached for comment.
Health officials had refused to renew the clinic’s license because, they said, they were unable to interview seven of its physicians over “potential deficient practices,” according to documents filed in a St. Louis court.
The legal battle in St. Louis comes a week after Missouri Governor Mike Parson, a Republican, signed a bill banning abortion beginning in the eighth week of pregnancy, making Missouri one of nine U.S. states to pass anti-abortion legislation this year.
On Friday, Stelzer said the clinic’s license would remain in effect until a ruling is made on Planned Parenthood’s request for a preliminary injunction against the state. A hearing on that matter is scheduled for 9 a.m. on Tuesday.
Outside the clinic on Friday, a handful of anti-abortion protesters stood holding “Choose Life” signs.
Abortion is one of the most socially divisive issues in U.S. politics, with opponents often citing religious beliefs to call it immoral, while abortion-rights advocates say the bans amount to state control of women’s bodies.
Anti-abortion activists say they aim to prompt the newly installed conservative majority on the U.S. Supreme Court to overturn Roe v. Wade by enacting laws that are virtually assured of facing court challenges.
A series of prominent U.S. media companies said they will rethink working in Georgia, if a new state law takes effect, banning abortions as soon as a fetal heartbeat can be detected by doctors. That standard effectively bans abortions at about six weeks into a pregnancy, before some women would even be aware they were pregnant.
Those companies include AT&T Inc’s WarnerMedia, CBS Corp, Viacom Inc, Comcast Corp’s NBCUniversal, AMC Networks Inc, Walt Disney Co and Netflix Inc.
Additional reporting by Gabriella Borter in New York; Editing by Scott Malone, Leslie Adler and David Gregorio
A Missouri State Flag waves outside the Reproductive Health Services of Planned Parenthood St. Louis Region, Missouri’s sole abortion clinic, in St. Louis, Missouri, U.S. May 28, 2019. REUTERS/Lawrence Bryant
NEW YORK (Reuters) – A Missouri court on Friday granted Planned Parenthood’s request for a temporary restraining order, letting the state’s only abortion clinic stay open until June 4 when another hearing will be held, according to a court order.
Planned Parenthood sued Missouri this week after state health officials said the license for Reproductive Health Services of Planned Parenthood in St. Louis was in jeopardy, meaning the clinic could have closed at midnight unless the judge granted the request for a temporary restraining order.
Reporting by Gabriella Borter; Writing by Daniel Wallis
WEDNESDAY, May 29, 2019 (HealthDay News) — New research delivers fresh hope for everyone who struggles with a fading memory: Neurons continue to form well into old age, even in people with mental impairments or Alzheimer’s disease.
“We found that there was active neurogenesis [new neurons forming] in the hippocampus of older adults well into their 90s,” said study author Orly Lazarov, a professor of anatomy and cell biology at the University of Illinois at Chicago.
“The interesting thing is that we also saw some new neurons in the brains of people with Alzheimer’s disease and cognitive [thinking] impairment,” she added in a university news release.
The findings could lead to new treatments for mental decline in older adults, the researchers said.
In the study, Lazarov and her colleagues examined hippocampus tissue from the brains of 18 people, average age 90.6 years, after they died.
The hippocampus is involved in the formation of memories and in learning.
On average, there were about 2,000 neural stem cells and 150,000 developing neurons in each brain.
While people with mental impairments and Alzheimer’s disease did have new neurons, their levels were significantly lower than in people with normal brain function, the researchers noted.
This is the first evidence of significant numbers of neural stem cells and newly developing neurons in the hippocampus of elderly adults, even in those with disorders that affect that part of the brain.
The researchers also found that people who scored better on tests of mental skills had more newly developing neurons in the hippocampus than those who scored lower on the tests, regardless of the level of disease in the brain.
“The mix of the effects of pathology and neurogenesis is complex and we don’t understand exactly how the two interconnect, but there is clearly a lot of variation from individual to individual,” Lazarov said.
“The fact that we found that neural stem cells and new neurons are present in the hippocampus of older adults means that if we can find a way to enhance neurogenesis, through a small molecule, for example, we may be able to slow or prevent cognitive decline in older adults, especially when it starts, which is when interventions can be most effective,” she said.
The findings were published May 23 in the journal Cell Stem Cell.
Hooked on tobacco? Make today, World “No Tobacco” Day, the perfect time to kick butts—cigarette butts, that is. This year’s theme is “tobacco and lung health.” According to the World Health Organization, tobacco smoking is the top cause for lung cancer, responsible for over two thirds of lung cancer deaths globally. Second-hand smoke exposure also increases risk of lung cancer.
When you stop smoking, you can reduce your risk of lung cancer. After 10 years of not smoking, your risk of lung cancer falls to about half that of a smoker.
If you’re ready to quit smoking or other tobacco use, Medicare can help. Medicare Part B covers up to 8 face-to-face counseling sessions in a 12-month period when you get them from a qualified doctor or other qualified health care provider. You pay nothing for these sessions if your doctor or other health care provider accepts assignment.
Visit the Centers for Disease Control and the National Cancer Institute to learn more about how you can quit smoking. You can also watch our video to learn more about how Medicare can help you kick the smoking habit.
A unique discovery about the nature of neutrophils — the most numerous white blood cells in the body — may lead to new models for diagnosing and tracking inflammatory diseases such as cancer and osteoarthritis.
The “first responders” of the body, neutrophils are a class of leukocyte immune cell in the “innate” immune system, which deals with acute infections. Billions of neutrophils are born in the bone’s marrow each day to protect the body and attack microbial invaders.
The general consensus in the past was that there is one kind of neutrophil in circulation in healthy people.”
Michael Glogauer, professor at the Faculty of Dentistry and acting chief dentist at the Princess Margaret Cancer Centre
“We found two distinct neutrophil states in blood, and these populations vary depending on the health of patient and if there are acute or chronic infections,” added Glogauer, who is one of the authors of the study, which appeared in Blood Advances this month.
The University of Toronto team discovered this unique subset of immune cells after developing a novel method of preserving and analyzing neutrophils in blood, overcoming a longstanding difficulty in how to study these short-lived and easily activated immune cells.
One population of neutrophils — primed neutrophils, or pPMNs — were discovered to be in a state of constant readiness to fight infections, comprising up to 10 per cent of the overall population of neutrophils. These were seen to be in contrast to the more abundant “resting state” neutrophils (rsPMNs), which circulate the blood in a naive state.
The team then tested blood samples from both mice with acute infections and humans with chronic gingivitis, tracking both the prime and resting neutrophils. When an acute infection flares up, the primed warrior cells quickly leave the blood stream and enter the tissues.
In both mouse and human models with acute inflammation, the primed cells disappear from the bloodstream and enter inflamed tissues within 15 minutes. Within one to three hours, the remaining resting state neutrophils also become activated, and follow the initial team into the tissues.
The current paradigm is that neutrophils are circulating in the blood, just waiting for something to happen, and then they are immediately recruited into tissue and fight infection.”
Noah Fine, postdoctoral fellow at the University of Toronto Faculty of Dentistry and first author of the study
“That’s still true,” adds Fine, “but we’re now looking at a model with a fine- tuned mechanism. In this model, the neutrophils aren’t constantly on a knife’s edge, waiting to react to an infection — that could lead to overexuberant neutrophil responses in healthy individuals.”
Neutrophil models for disease prediction
The discovery may one day aid in disease detection and monitoring. If the percentage of primed neutrophils in the blood is constant in a healthy state, hovering at around 10 per cent, then it follows that “we can track the state of the activation of the innate immune system where the expectation would be elevated levels of this primed population,” says Glogauer.
Blood samples from those who are experiencing inflammatory disease attacks, for instance, can be looked at for the number of primed neutrophils as a barometer of the activation state of the immune system — telling medical professionals exactly how acute an infection is across a wide range of inflammatory diseases such as cancer, gout, arthritis and diabetes.
Currently, the team is testing neutrophil populations both just before and after cardiovascular surgery, as well as patients with rheumatoid arthritis and periodontitis.
The discovery may also lead to new paradigms for health research.
“The fact that we see this population in mice and that it appears to behave similarly in humans is very exciting,” says Fine, who points out that mice and other animal models used in health research sometimes have limitations based on their physiological differences to humans.
The neutrophil populations, in contrast, appear to be similar across mammals, according to the researchers.
University of Toronto – Faculty of Dentistry
Fine, N. et al. (2019) Primed PMNs in healthy mouse and human circulation are first responders during acute inflammation. Blood Advances. doi.org/10.1182/bloodadvances.2018030585.
Scientists have identified a new internal regulator which helps control the body’s response to fight infection.
The discovery could be a target for new drugs to tackle autoimmune diseases, such as lupus and scleroderma, where healthy tissues are attacked by the body’s own immune system.
We want to put a brake on the body’s own immune system to stop it turning on itself. Our discovery has the potential to help us find a new drug to target this regulator, to suppress the immune system and stop the body destroying its own cells, even when there is no infection present. We’re a long way off being able to find a new effective treatment for autoimmune disease, but we’re excited because this discovery could open the door to a new class of drugs.”
Dr Elton Zeqiraj, University of Leeds.
Autoimmune diseases include a wide range of difficult-to-treat conditions, including Type 1 diabetes and rheumatoid arthritis.
The scientists used powerful cryo-electron microscopes at the University of Leeds’ Astbury Centre to reveal the structure of the regulator, comprised of two proteins in the body called BRISC and SHMT2, to understand for the first time how they work together in a cell.
The protein complex acts to increase the immune response of cells, which occurs when they detect an invading pathogen.
Dr Elton Zeqiraj continued: “The microscopes have allowed us to understand the structure of this protein complex in superb detail, and by building an accurate 3D model, we discovered that it plays a completely unexpected role in regulating our immune response.
“The next step is to find a way of targeting this protein to inhibit the process, to prevent our immune system from attacking healthy cells.”
Once the structure had been revealed, it was possible to design genetically engineered versions of the proteins and map out the functions of this complex in cells.
The scientists also discovered, rather unexpectedly, that the BRISC-SHMT2 protein complex can be regulated by the active form of vitamin B6.
Although vitamin B6 was shown to be important in the function of this regulator, the scientists caution that further research is needed to fully understand the role that it plays.
The findings have been published in the scientific journalNature, and the team have created the world’s first visual of the protein complex.
The research was carried out by an international team of researchers and clinicians, led by the University of Leeds and the University of Pennsylvania.
Co-lead author Dr Roger Greenberg at the University of Pennsylvania, said: “We now have an unprecedented understanding of how this protein complex functions at atomic resolution. It reveals the molecular basis underlying communication between metabolism and immune responses, while also pointing to new ways to prevent the action of this complex in diseases stemming from overactive inflammatory signals.”
Co-author Dr Francesco Del Galdo, from the University of Leeds, said: “Targeted therapies have revolutionised the way we manipulate the immune system and this discovery is giving us crucial insights on the role of metabolism in regulating innate immunity.”
The SHMT2 protein is one of a small, but growing number of molecules that are involved in both cell metabolism and immune responses, so the team were very surprised by their findings.
Dr Elton Zeqiraj first began researching the structure of this protein complex in 2010, at the Mount Sinai Hospital in Toronto, Canada, before moving in 2016 to Leeds to work in the Astbury Centre for Structural Molecular Biology.
Dr Zeqiraj said: “The Astbury Centre in Leeds has one of the best structural biology facilities in the world, and having access to such a facility and expertise was essential. This breakthrough would not have been possible without the University’s state-of-the-art microscopes, which have allowed us to understand this protein’s structure for the first time.”
The international collaboration of scientists and clinicians included co-first authors Dr Miriam Walden from Leeds and Dr Lei Tian from Pennsylvania, as well as researchers from the University of Liverpool, The Wistar Institute (Philadelphia), UbiQ Bio BV (Amsterdam), Warsaw University of Life Sciences and Lund University.
The research was primarily funded by the Wellcome Trust, The Royal Society, the National Cancer Institute, the Lupus Research Alliance, and Scleroderma and Raynaud’s UK.
Sumi Subramaniam, Infection and Immunobiology Portfolio Manager at Wellcome, said: “This study uses cutting-edge technology to unravel the fundamental biological function of two proteins and how they interact to control the body’s immune response to an infection.
“Disrupting these proteins could be an exciting new avenue to explore in tackling autoimmune diseases, where the immune system attacks healthy cells. We have very few effective treatments for autoimmunity, and these findings could help researchers to find new ways to control the immune response.”
Sue Farrington, Chief Executive of Scleroderma and Raynaud’s UK, said: “Thousands of people in the UK are suffering from autoimmune diseases like scleroderma, which can cause serious skin problems that can greatly reduce quality of life.
“We are very proud to have helped fund this important scientific breakthrough, and we hope this can open up a new avenue for drug discovery so that we can create more effective treatments for autoimmune conditions.”
University of Leeds
Walden, M. et al. (2019) Metabolic control of BRISC–SHMT2 assembly regulates immune signalling. Nature. doi.org/10.1038/s41586-019-1232-1.
BUTEMBO, Democratic Republic of Congo (Reuters) – Eight-year-old Kennedy Muhindo was running a high fever and racked by stomach pain and diarrhea.
Health workers told him he had Ebola but his first thought was for his sister who had been battling the virus.
“How is my big sister doing?” he asked health workers again and again at an Ebola treatment center on the outskirts of Butembo, a major trading hub set amid volcanic hills in eastern Democratic Republic of Congo.
Staff said they didn’t have the heart to tell him that 9-year-old Lareine had died.
“His sister was his best friend,” said Desy Shabani, who provides psycho-social support to the patients. “To have lost the dearest person in his life . . . I asked myself, ‘What will this child do?’”
The Ebola outbreak in Congo – the second-largest on record – has inflicted an unusually heavy toll on children. More than a quarter of the confirmed and probable cases identified as of early April were children under 15, compared to 18% in the last major outbreak in West Africa in 2013-2016, according to figures compiled by the World Health Organization.
The disease can progress rapidly, crippling the immune system and shutting down vital organs.
Young children and babies are especially vulnerable. Their small bodies are less well equipped to cope with extreme fluid loss brought on by common symptoms such as diarrhea, vomiting, fever and bleeding, said Daniel Bausch, an infectious disease specialist at the London School of Hygiene and Tropical Medicine.
More than two out of every three children infected in this outbreak have died compared with just over half the adults, the WHO said. As of May 26, the death toll stood at 1,281 people, including at least 541 who were under 18.
Fatality rates are highest for children under 4 who died at a rate of around 80% in West Africa, according to a study published in the New England Journal of Medicine in 2015.
More than 11,000 people in all died in that outbreak.
The contents of the storage room at the Butembo treatment center attest to the age of many of the patients. Alongside blankets and spare clothes stand shelves full of baby formula and neon-colored plastic rattles in the shape of little bears.
In the city center, small coffins wrapped in flowery plastic were stacked outside a carpenter’s shop. An employee lamented the frequency of orders.
GLOVES AND BODILY FLUIDS
Ebola cases would typically be divided more or less equally between male and female patients. But in this outbreak, women and girls account for 58% of cases, down from a peak of 62% in December, the WHO said.
The reason more women and children have fallen sick remains a bit of a mystery. But experts suspect it may be because the Beni area, where the outbreak began in August, was also battling malaria at the time.
Malaria can cause severe complications in pregnant women and children, requiring treatment at medical facilities where they risk exposure to undiagnosed Ebola patients, said Mike Ryan, who heads the WHO’s health emergencies program.
“Transmission within the healthcare setting has been a major factor driving this outbreak,” Ryan said. “Unfortunately, women and children have been the unwitting victims of that reality.”
Healthcare standards in Congo vary widely due to lack of oversight over a system that includes many unregistered private clinics and traditional healers operating out of their homes.
The virus is transmitted through contact with infected bodily fluids. But health workers operating outside of government hospitals do not always follow guidelines to prevent cross-contamination, according to Congo’s health ministry.
“It means at times they don’t change gloves or don’t use single-use ones or simply they don’t use gloves at all,” said Jessica Ilunga, a ministry spokeswoman. “They don’t sterilize their equipment, and they don’t decontaminate beds, and they don’t change sheets.”
Anselme Mungwayitheka said he and two other health workers at a private clinic in Beni caught Ebola from a woman and her newborn who were infected while in the care of a traditional healer.
Desy Shabani, a psycho-social assistant, talks to suspected Ebola patients at an Ebola treatment centre in Butembo, in the Democratic Republic of Congo, March 27, 2019. REUTERS/Baz Ratner
“We didn’t have much equipment in this facility,” said Mungwayitheka, who now works at an Ebola treatment center in Beni he credits with saving his life. “When we received patients, we just had to put on protective gloves. After caring for them, we had to remove the gloves, but the patient had touched almost all the doors.”
A key part of the Ebola response effort involves decontaminating health facilities, educating health workers on how to protect themselves and their patients, and persuading residents to seek treatment at specialized centers. But these efforts have been hindered by outbreaks of violence and a deep mistrust of outsiders.
This is Congo’s tenth Ebola outbreak, but it is the first in the densely populated provinces of North Kivu and Ituri, where militias carry out sporadic raids from hidden strongholds in the tropical forest. Women and children are often the first to be displaced by the bloodshed.
‘ALL OF THEM COULD HAVE DIED’
At the Ebola treatment center in Beni, a city of several hundred thousand with close ties to neighboring Uganda, five members of the same family of farmers were being treated for Ebola in late March. Three were children.
Marcela Kaswera, 45, said she had sent her children to their older brother in the village of Biakatu after their hometown of Oicha was attacked by members of an Islamist militia.
“On March 20, it was a Wednesday, my son called me,” Kaswera recalled. “He said, ‘Mama, I’m coming back to Oicha because Ebola has touched Biakatu, and many people are dying.’”
When they returned, her 7-year-old son was feverish. He died in her arms at a hospital, where he posthumously tested positive for Ebola.
In quick succession, Kaswera’s 13-year-old son, 2-year-old daughter, grown-up son, daughter-in-law and grandson all developed symptoms of the virus and were transferred to the treatment center run by the Alliance for International Medical Action.
“Now I can thank God because they are stable,” said Kaswera, who had traveled 30 kilometers (19 miles) on the back of a motorbike taxi with her husband to visit their sick family members. “If it was just me without doctors I think all of them could have died.”
On the evening of Feb. 27, unknown assailants attacked the center in Butembo where Kennedy was being treated, setting fire to some structures and vehicles. Hearing gunshots, one of the other patients took the boy and fled through open fields into the city. They spent the night at the man’s home and returned the next day.
Slideshow (9 Images)
“He was really scared,” recalled Shabani, standing on a walkway outside a line of tented cubicles, where people with suspected Ebola waited for test results.
Kennedy was discharged less than a week later. He is now back at school and plays football with a gaggle of children on the steep, muddy streets near his home, bordering lush farmland.
GENEVA (Reuters) – Children under five infected with Ebola in eastern Democratic Republic of Congo are dying at a higher rate than other patients as their parents shun special treatment centers, the World Health Organization (WHO) said on Thursday.
FILE PHOTO: Rachel Kahindo, an Ebola survivor working as a caregiver to babies who are confirmed Ebola cases, holds an infant outside the red zone at the Ebola treatment centre in Butembo, Democratic Republic of Congo, March 25, 2019. REUTERS/Baz Ratner/File Photo
Three out of four of the under-fives, or 77%, are succumbing to the disease, compared with 57% for older youngsters and 67% for all infected people, the U.N. body said in a new analysis of the epidemic – the world’s second worst on record.
Many under-fives are not taken to Ebola treatment centers, known as ETCs, where survival rates are markedly higher, but instead visit multiple healthcare facilities that are not as well-equipped to provide treatment or isolation, the WHO said in a weekly update.
This “may be out of fear of being far from home and without the support of family members”, but could help spread the virus, a form of hemorrhagic fever, it said.
“All cases that may not be adequately isolated, including children under five-years of age, may pose a considerable transmission risk to healthcare workers, patients, and members of the community,” it said.
Children under five are also less likely than older youth to be included on lists of possible contacts exposed to the disease, who require surveillance or vaccination, it said, calling for improved tracing and monitoring.
“More work needs to be done to reduce fear and misunderstanding of ETCs and to reduce any other barriers to access, with a special focus on this age group,” it said.
Under-fives account for 15%, or 300 of the 1,945 cases reported since the epidemic began last August, the WHO said. In all, 1,302 people have died.
Congo’s outbreak has inflicted an unusually heavy toll on children. More than a quarter of the confirmed and probable cases identified as of early April were children under 15, compared to 18% in the last major outbreak in West Africa in 2013-2016, according to figures compiled by the Geneva-based WHO.
Fatality rates for both under and over 5s were in line with those observed in the West Africa outbreak, it said.
WEDNESDAY, May 29, 2019 (HealthDay News) — Here’s another reason to keep your cholesterol under control: New research suggests that LDL, or “bad,” cholesterol may play a role in the development of early-onset Alzheimer’s.
A rare form of the disease that occurs before the age of 65, early-onset Alzheimer’s has previously been linked to a gene mutation involved in how the body processes fats and cholesterol. But that mutation only accounts for a small percentage of cases, the scientists noted.
Their new research suggests that “LDL cholesterol levels [also] play a causal role in the pathogenesis of Alzheimer’s disease,” said lead researcher Dr. Thomas Wingo. He’s an assistant professor of neurology at Emory University School of Medicine in Atlanta.
“The big question is whether there is a causal link between cholesterol levels in the blood and Alzheimer’s disease risk,” Wingo said. “The existing data is murky on this point. Our current work is focused on testing whether there is a causal link.”
Most early-onset Alzheimer’s disease is not explained by known gene mutations, Wingo added.
The APOE genetic mutation, called APOE E4, raises levels of LDL cholesterol. High levels of this type of cholesterol can clog arteries, increasing the risk for heart attack and stroke.
Other gene mutations associated with early-onset Alzheimer’s are called APP, PSEN1 and PSEN2.
But all of these genetic variants are only linked to about 10% of all cases of early-onset Alzheimer’s. That leaves 90% of all early-onset Alzheimer’s unexplained, Wingo said.
For the study, he and his colleagues sequenced specific areas of the genes of more than 2,100 people. Of these, more than 650 suffered from early-onset Alzheimer’s. In addition, more than 260 participants had their cholesterol levels checked.
The researchers found that the APOE E4 mutation accounted for about 10% of early-onset Alzheimer’s, which is the same as seen in late-onset Alzheimer’s.
They also looked for APP, PSEN1, and PSEN2 mutations, and found that about 3% of early-onset Alzheimer’s patients had at least one of these variants.
Wingo’s team also found that participants with high LDL cholesterol levels were at a greater risk for early-onset Alzheimer’s, compared with those with lower LDL levels.
LDL cholesterol levels remained salient even after taking APOE mutations into account. Thus, cholesterol may be an independent risk factor for early-onset Alzheimer’s, Wingo said, though the study did not prove that high LDL cholesterol levels caused early-onset Alzheimer’s.
No link was found between Alzheimer’s and HDL (“good”) cholesterol. A slight association was seen, however, with triglyceride levels.
A link between LDL cholesterol and early-onset Alzheimer’s was not completely explained by APOE or an even rarer gene mutation known as APOB, which suggests that factors including other genes may increase the risk, Wingo said.
“If there is a causal link between Alzheimer’s disease and cholesterol, we might need to revise targets for LDL cholesterol levels to help reduce Alzheimer’s risk,” he said.
Dr. Sam Gandy, director of the Mount Sinai Center for Cognitive Health, and NFL Neurological Care in New York City, said these findings are credible and likely to be replicated in the coming months.
This finding confirms a longstanding suspicion that cholesterol is one of the major players in Alzheimer’s disease, he said.
This is especially noteworthy because it can have major implications for treatment, said Gandy, who wasn’t involved with the study. “It’s a very exciting counterpoint to continued loss of enthusiasm for directly targeting amyloid plaques in the brain,” he said.
For years, the buildup of those protein plaques in the brain had been thought to be a possible cause of Alzheimer’s, but recent drug trials aimed at lowering amyloid have shown little effect on the disease.
The report was published online May 28 in the journal JAMA Neurology.
SOURCES: Thomas Wingo, M.D., assistant professor, neurology, Emory University School of Medicine, Atlanta; Sam Gandy, M.D., Ph.D., professor, neurology and psychiatry, Icahn School of Medicine, New York City, and director, Mount Sinai Center for Cognitive Health, and NFL Neurological Care, New York City; May 29, 2019, JAMA Neurology, online
Pioneering research by scientists at the Universities of Oxford and Birmingham published today [May 29th] in Nature brings us a step closer to developing targeted therapies for inflammatory diseases.
The research team shows, for the first time, that different types of fibroblasts – the most common cells of connective tissue in animals – are organized in different layers in the joint and are responsible for two very different forms of arthritis; osteoarthritis and rheumatoid arthritis.
Targeted therapies could alter the behavior of fibroblasts to reduce inflammation and tissue destruction in these two diseases without the need for long-term immunosuppression or joint replacements, say the scientists.
The research was supported by Wellcome Trust, Versus Arthritis, and NIHR Birmingham Biomedical Research Centre, which is based at University Hospitals Birmingham NHS Foundation Trust and the University of Birmingham.
The research is part of the Arthritis Therapy Acceleration Programme (A-TAP), a joint alliance between the Universities of Birmingham and Oxford, which aims to ensure that world-class basic science observations are accelerated into early-phase experimental therapy for patients. A-TAP is funded by the Kennedy Trust for Rheumatology Research at the University of Oxford.
Chief investigator Professor Chris Buckley, of the University of Birmingham’s Institute of Inflammation and Ageing and Director of Clinical Research at the Kennedy Institute at the University of Oxford:
If we compare fibroblasts to soil, this research has shown for the first time that not all soil is the same.
Just as there are different layers of soil in our gardens – top soil and subsoil – there are different types of fibroblasts in our joints – and each layer seems to be associated with a different type of arthritis.
From a research perspective this is exciting, but the clinical implications are also very important too. For the first time, we have identified two different types of fibroblasts in the joint, which, just like the different types of soil, lead to different types of arthritis.
The top soil is what goes wrong in osteoarthritis, whereas in rheumatoid arthritis it’s the subsoil that is at fault.
When patients are seen in clinic and we can’t help them, it motivates us to think creatively about how we conduct our research and classify disease.
We have now discovered a new way to classify, and therefore treat, arthritis based on the underlying cell, rather than just the clinical features and genes involved.
Current therapies work like weed killer – they kill the weeds but the weeds come back if you don’t continue to apply the weed killer. Our research will facilitate research aimed at changing the top soil, subsoil – or both – to treat arthritis.
To know we are getting closer to offering patients new solutions is very exciting and we are doing it because we are finally looking at diseases using a process-driven cell based approach through the A-TAP project.”
Two recent technical and clinical advances have helped lead to the researchers’ discovery: minimally invasive biopsies and single-cell sequencing. These two developments have allowed the research team to investigate fibroblast cells and their location in the joint as never before, ultimately identifying and describing the biology of distinct subsets of fibroblasts responsible for mediating either inflammation or cartilage/bone damage in arthritis.
First author Dr Adam Croft, currently NIHR Academic Clinical Lecturer in Rheumatology at the University of Birmingham and previously funded by a Wellcome Trust Clinical Career Development Fellowship, adds: “Rheumatoid arthritis is challenging to treat. It causes chronic inflammation in joints, leading to pain, swelling and, over time, damage to the joint. This is due to the body’s own immune system attacking the joints, which leads to an influx of immune cells in the lining of the joint.
“Current treatments target these immune cells either directly or by trying to disrupt the signals that attract the cells to the joint. No treatments directly target fibroblasts, key effector cells in the pathology of this disease.
“Thanks to advances in technology we have now, for the first time, been able to identify which fibroblasts are pathogenic in arthritis and how they contribute to disease.
Importantly, we found that by getting rid of these fibroblasts from the joint we could reduce the influx of immune cells to the joint, leading to less inflammation and destruction.
“These findings mean we now have a clear rationale for developing drugs that can target joint fibroblasts directly and provide more effective treatment for persistent disease.”
University of Birmingham
Croft P A,et al. (2019) Distinct fibroblast subsets drive inflammation and damage in arthritis. Nature. doi.org/10.1038/s41586-019-1263-7.