COVID-19, in its multiple variants and its ability to thwart efforts to wipe it out, still has a lot of unknowns that make it impossible for scientists to declare victory over the disease, despite vaccines.
But now two Université de Montréal professors working at the Montreal Institute for Clinical Research (IRCM) have taken a big step towards understanding the coronavirus: they've identified and confirmed the power of two small molecules to block the infection of lung cells by SARS-CoV-2, the virus that causes COVID-19.
The finding by the teams of medical professor Nabil G. Seidah, the IRCM's director of biochemical neuroendocrinology research, and microbiology professor Éric A. Cohen, the IRCM's director of human retrovirology research, was published Monday in the Journal of Virology.
Trial shows arthritis drug restores hair in a third of alopecia patients
By Nick Lavars
March 31, 2022
In pursuit of a treatment for alopecia areata, an autoimmune disorder that causes hair loss, scientists have found new success by repurposing a common arthritis drug. An impressive portion of trial participants were able to regrow their hair following regular doses of the medication, offering fresh hope for an approved treatment for the condition.
Alopecia areata is the result of the immune system attacking hair follicles, causing patchy hair loss to particular areas of the scalp, or sometimes the eyebrows and lashes. It is the type famously suffered by the actress Jada Pinkett Smith, but in fact around 200,000 new cases occur in the US every year, mostly affecting those under the age of 40. There are currently no FDA-approved treatments for the disorder.
Scientists at Yale University have been exploring the potential of a common rheumatoid arthritis drug called baricitinib as a solution, based on the premise that it is an autoimmune treatment that could interrupt the cytokine signaling that harms the hair follicles. Their latest trials involved around 1,200 people with severe alopecia areata, who had lost at least half of their hair as a result.
Over the years, everyone loses a few brain cells. A study led by scientists from USC Stem Cell and the USC Neurorestoration Center presents evidence that adults can replenish at least some of what they've lost by generating new brain cells, and that this process is dramatically altered in patients with long-term epilepsy. The findings are published in Nature Neuroscience.
"Our study is the first to detail the presence of newborn neurons and an immature version of a related cell type, known as astroglia, in patients with epilepsy," said Michael Bonaguidi, an assistant professor of stem cell biology and regenerative medicine, gerontology, and biomedical engineering at USC. "Our findings furnish surprising new insights into how immature astroglia might contribute to epilepsy—opening an unexplored avenue toward the development of new anti-seizure medications for millions of people."
EPA rule would finally ban asbestos, carcinogen still in use
Source: AP
WASHINGTON (AP) — The Environmental Protection Agency on Tuesday proposed a rule to finally ban asbestos, a carcinogen that is still used in some chlorine bleach, brake pads and other products and kills thousands of Americans every year. The proposal marks a major expansion of EPA regulation under a landmark 2016 law that overhauled rules governing tens of thousands of toxic chemicals in everyday products, from household cleaners to clothing and furniture. The proposed rule would ban chrysotile asbestos, the only ongoing use of asbestos in the United States.
The substance is found in products such brake linings and gaskets, and is used to manufacture chlorine bleach and sodium hydroxide, also known as caustic soda. EPA Administrator Michael Regan called the rule an important step to protect public health and “finally put an end to the use of dangerous asbestos in the United States.″ The proposed ban “demonstrates significant progress in our work to implement the (2016) law and take bold, long-overdue actions to protect those most vulnerable among us,” Regan said. The 2016 law authorized new rules for tens of thousands of toxic chemicals found in everyday products, including substances such as asbestos and trichloroethylene that for decades have been known to cause cancer yet were largely unregulated under federal law.
Known as the Frank Lautenberg Chemical Safety Act, the law was intended to clear up a hodgepodge of state rules governing chemicals and update the Toxic Substances Control Act, a 1976 law that had remained unchanged for 40 years. The EPA banned asbestos in 1989, but the rule was largely overturned by a 1991 court decision that weakened EPA’s authority under TSCA to address risks to human health from asbestos or other existing chemicals. The 2016 law required the EPA evaluate chemicals and put in place protections against unreasonable risks.
At the signing ceremony for the new law, then-President Barack Obama said the U.S. chemical system under TSCA was “so complex, so burdensome that our country hasn’t even been able to uphold a ban on asbestos. I think a lot of Americans would be shocked by all that.” Asbestos, which was once common in home insulation and other products, is banned in more than 50 countries and its use in the U.S. has been declining for decades. The only form of asbestos known to be currently imported, processed or distributed for use in the U.S. is chrysotile asbestos, which is imported primarily from Brazil and Russia. It is used by the chlor-alkali industry, which produces bleach, caustic soda and other products.
Australian researchers have discovered a new neurodevelopmental disorder after uncovering its link to a tumor suppressor gene.
The international research collaboration, led by the Murdoch Children's Research Institute (MCRI) and published in the American Journal of Human Genetics, has linked a recognized tumor suppressor gene to a new neurodevelopmental syndrome, ending the diagnostic journey for 32 families around the world.
The study found variations in the FBXW7 gene were associated with the newly identified condition, which causes mild to severe developmental delay, intellectual disability, hypotonia and gastrointestinal issues.
Murdoch Children's researcher Dr. Sarah Stephenson said because the FBXW7 gene regulated the life-cycle of cells, cell growth and survival, the research team speculated that abnormal cell proliferation during brain development may underpin the broad spectrum of brain abnormalities identified in this new disorder.
"FBXW7 now joins a steeply increasing number of intellectual disability/autism spectrum disorder genes that have been implicated in disorders that affect nervous system development, leading to atypical brain function, affecting emotion, learning ability, self-control and memory," she said.
The study used cutting-edge diagnostic tools, genomic sequencing and global data sharing platforms to identify 35 people, aged 2-44 years, from 32 families in seven countries harboring the FBXW7 gene, which had variants that were associated with the never-before described neurodevelopmental syndrome.
Researchers Identified over 5,500 New Viruses in the Ocean, Including a Missing Link in Viral Evolution by Guillermo Dominguez Huerta, Ahmed Zayed, James Wainaina, and Matthew Sullivan
An analysis of the genetic material in the ocean has identified thousands of previously unknown RNA viruses and doubled the number of phyla, or biological groups, of viruses thought to exist, according to a new study our team of researchers has published in the journal Science.
RNA viruses are best known for the diseases they cause in people, ranging from the common cold to COVID-19. They also infect plants and animals important to people.
These viruses carry their genetic information in RNA, rather than DNA. RNA viruses evolve at much quicker rates than DNA viruses do. While scientists have cataloged hundreds of thousands of DNA viruses in their natural ecosystems, RNA viruses have been relatively unstudied.
Unlike humans and other organisms composed of cells, however, viruses lack unique short stretches of DNA that could act as what researchers call a genetic bar code. Without this bar code, trying to distinguish different species of virus in the wild can be challenging.
To get around this limitation, we decided to identify the gene that codes for a particular protein that allows a virus to replicate its genetic material. It is the only protein that all RNA viruses share, because it plays an essential role in how they propagate themselves. Each RNA virus, however, has small differences in the gene that codes for the protein that can help distinguish one type of virus from another.
Most autoimmune diseases are easy to diagnose but hard to treat. A paper published today in Science proposes using your unique immune cell fingerprint to rapidly identify which treatments will work for your autoimmune disease.
"We analyzed the genomic profile of over one million cells from 1,000 people to identify a fingerprint linking genetic markers to diseases such as multiple sclerosis, rheumatoid arthritis, lupus, type 1 diabetes, spondylitis, inflammatory bowel disease, and Crohn's disease," says Professor Joseph Powell, joint lead author at the Garvan Institute of Medical Research. "We were able to do this using single cell sequencing, a new technology that allows us to detect subtle changes in individual cells," he says.
The discovery could help individuals find tailored treatments that work for them and guide the development of new drugs.
The study by researchers in Sydney, Hobart, Melbourne, Brisbane and San Francisco helps us understand why some treatments work well in some patients, but not in others. It's the largest study to date to link disease-causing genes to specific types of immune cells.
A trial is now underway in Sydney with Crohn's disease patients to predict which treatments will work for specific patients.
In a paper published today in Sciences Advances, researchers in the Department of Chemistry and the Department of Physics & Astronomy at the University of California, Irvine revealed new details about a key enzyme that makes DNA sequencing possible. The finding is a leap forward into the era of personalized medicine when doctors will be able to design treatments based on the genomes of individual patients.
Scientists have provided the strongest evidence yet that a protein that enables us to detect the sensation of cold may also be responsible for migraines. The findings appear in the journal Pain.
The findings move TRPM8 into the light as a potential target for new drugs aimed at relieving migraine.
"Our results confirm the importance of TRPM8 in migraines that was suggested by human genome-wide association studies and implicate the protein as a potentially important component of the pathology that leads to migraine. Thus, other scientists or clinicians can now add TRPM8 to their models of migraine and potential targets for treatment," says David McKemy, professor of biological sciences at USC Dornsife and corresponding author on the study.
Psilocybin, the psychedelic compound found in magic mushrooms, helps to "open up" depressed people's brains, even after use, enabling brain regions to talk more freely to one another.
These are the findings of a new analysis of brain scans from close to 60 people receiving treatment for depression, led by Imperial College London's Centre for Psychedelic Research. The team behind the study believes it may have untangled how psilocybin exerts its therapeutic effects on the brain.
Psilocybin is one of a number of psychedelics being explored as a potential therapy for psychiatric disorders. Several studies have trialed a synthesized form of the drug to treat patients with depression and anxiety, with promising results.
The new results, taken from two combined studies, reveal that people who responded to psilocybin-assisted therapy showed increased brain connectivity not just during their treatment, but up to three weeks afterwards. This "opening up" effect was associated with self-reported improvements in their depression. However, similar changes in brain connectivity were not seen in those treated with a conventional antidepressant (called escitalopram), suggesting the psychedelic works differently in treating depression.
A new study by scientists at The Picower Institute for Learning and Memory at MIT provides the most comprehensive and rigorous evidence yet that the mammalian brain stores a single memory across a widely distributed, functionally connected complex spanning many brain regions, rather than in just one or even a few places.
Memory pioneer Richard Semon had predicted such a "unified engram complex" more than a century ago, but achieving the new study's affirmation of his hypothesis required the application of several technologies developed only recently. In the study, the team identified and ranked dozens of areas that were not previously known to be involved in memory and showed that memory recall becomes more behaviorally powerful when multiple memory-storing regions are reactivated, rather than just one.
Demand for new kinds of antibiotics is surging, as drug-resistant and emerging infections are becoming an increasingly serious global health threat. Researchers are racing to reexamine certain microbes that serve as one of our most successful sources of therapeutics: the actinomycetes.
Scientists at Washington University in St. Louis and the University of Hawaii discovered a potential candidate for drug development from one such microbe, the soil bacterium known as Lentzea flaviverrucosa. They reported their findings in a study published the week of April 11 in the Proceedings of the National Academy of Sciences.
"Rare actinomycetes are an underexploited source of new bioactive compounds," said Joshua Blodgett, assistant professor of biology in Arts & Sciences, co-corresponding author of the new study. "Our genomics-based approach allowed us to identify an unusual peptide for future drug design efforts."
Actinomycetes produce bioactive components that form the basis for many clinically useful drugs, especially antibiotics and anticancer agents. Since the 1940s, pharmaceutical companies have analyzed many common actinomycetes to see what they might produce. Today, about two-thirds of all antibiotics used in hospitals and clinics are derived in part from actinomycetes.
To a certain extent, kidneys have the capacity to repair themselves after being injured, but a switch can occur from such intrinsic repair to incomplete repair that leads to irreversible damage and chronic kidney disease (CKD). A team led by researchers at Massachusetts General Hospital (MGH) recently used kidney organoids derived from human stem cells to identify genes that are important for maintaining healthy repair in the kidneys. The findings, which are published in Science Translational Medicine, may lead to new targets to help prevent or treat CKD.
Although various factors involved in kidney repair have been identified in animal studies, translating these findings into the clinical been difficult because many treatments deemed safe and effective in animals have subsequently been found to be toxic or ineffective in clinical trials. Human kidney organoids, which are like miniature kidneys, may help investigators avoid these setbacks.
"We have pioneered the work of human kidney organoids and think they'll be useful for therapeutic development for CKD," says lead author Navin Gupta, MD, an investigator in the Division of Nephrology at MGH. "As physician-scientists, we wanted to create a new CKD model in human cells to facilitate drug development."
Microfluidic devices are compact testing tools made up of tiny channels carved on a chip, which allow biomedical researchers to test the properties of liquids, particles and cells at a microscale. They are crucial to drug development, diagnostic testing and medical research in areas such as cancer, diabetes and now COVID-19. However, the production of these devices is very labor-intensive, with minute channels and wells that often need to be manually etched or molded into a transparent resin chip for testing. While 3D printing has offered many advantages for biomedical device manufacturing, its techniques were previously not sensitive enough to build layers with the minute detail required for microfluidic devices. Until now.
Researchers at the USC Viterbi School of Engineering have now developed a highly specialized 3D-printing technique that allows microfluidic channels to be fabricated on chips at a precise microscale not previously achieved. The research, led by Daniel J. Epstein Department of Industrial and Systems Engineering Ph.D. graduate Yang Xu and Professor of Aerospace and Mechanical Engineering and Industrial and Systems Engineering Yong Chen, in collaboration with Professor of Chemical Engineering and Materials Science Noah Malmstadt and Professor Huachao Mao at Purdue University, was published in Nature Communications.
The research team used a type of 3D printing technology known as vat photopolymerization, which harnesses light to control the conversion of liquid resin material into its solid end state.
UCLA scientists and colleagues have created a first-of-its-kind roadmap that traces each step in the development of blood stem cells in the human embryo, providing scientists with a blueprint for producing fully functional blood stem cells in the lab.
The research, published today in the journal Nature, could help expand treatment options for blood cancers like leukemia and inherited blood disorders such as sickle cell disease, said Dr. Hanna Mikkola of the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA, who led the study.
Blood stem cells, also called hematopoietic stem cells, have the ability to make unlimited copies of themselves and to differentiate into every type of blood cell in the human body. For decades, doctors have used blood stem cells from the bone marrow of donors and the umbilical cords of newborns in life-saving transplant treatments for blood and immune diseases. However, these treatments are limited by a shortage of matched donors and hampered by the low number of stem cells in cord blood.
Researchers have sought to overcome these limitations by attempting to create blood stem cells in the lab from human pluripotent stem cells, which can potentially give rise to any cell type in the body. But success has been elusive, in part because scientists have lacked the instructions to make lab-grown cells differentiate into self-renewing blood stem cells rather than short-lived blood progenitor cells, which can only produce limited blood cell types.
"Nobody has succeeded in making functional blood stem cells from human pluripotent stem cells because we didn't know enough about the cell we were trying to generate," said Mikkola, who is a professor of molecular, cell and developmental biology in the UCLA College and a member of the UCLA Jonsson Comprehensive Cancer Center.
A team of researchers at Atara Biotherapeutics has conducted a small Phase I clinical trial of a therapeutic called ATA188 that targets Epstein-Barr infections (EBV) as a treatment for multiple sclerosis (MS). Representatives from Atara Biotherapeutics presented their findings at an EBV and MS Day event. A press release from late last year described the results of their clinical trial.
MS is a disease of the central nervous system in which the immune system attacks the sheath that covers and protects nerve cells. And EBV is a virus also known as human herpesvirus 4; it is one of the most common viral infections in humans. Some scientists have estimated that approximately 95% of people alive today have been infected by the virus at some point. In addition to being the root cause of mononucleosis, it is believed to play a role in several autoimmune diseases such as chronic fatigue syndrome, encephalomyelitis and possibly MS. Prior research has shown that the virus enters a dormant state after attack by the immune system, only to reemerge later, causing difficult-to-isolate problems.
A brighter future could be in store for people with a spinal cord injury if new animal research pans out in humans.
Mice that were paralyzed due to severe spinal cord damage regained the ability to walk within four weeks of receiving an experimental injectable therapy, say researchers led by Samuel Stupp of Northwestern University in Chicago.
The research team plans to seek U.S. Food and Drug Administration approval for the treatment to be used in people.
"Our research aims to find a therapy that can prevent individuals from becoming paralyzed after major trauma or disease," said Stupp, a professor of materials science and engineering, chemistry, medicine and biomedical engineering.
"For decades, this has remained a major challenge for scientists because our body's central nervous system, which includes the brain and spinal cord, does not have any significant capacity to repair itself after injury or after the onset of a degenerative disease," Stupp said in a university news release.
In people with immune thrombocytopenia (ITP), the body produces destructive antibodies against platelets in the blood, which increases the risk of bruising, bleeding, hospitalization, death, fatigue, and an impaired quality of life. A drug called rilzabrutinib has generated promising safety and efficacy results in a recent international multi-center phase 1–2 ITP trial led by investigators at Massachusetts General Hospital (MGH). The findings, which are published in the New England Journal of Medicine, pave the way for more advanced clinical trials.
Research has shown that cells called macrophages are primarily responsible for destroying antibody-coated platelets in ITP, and an enzyme called Bruton kinase is critical to their function. Although an inhibitor of Bruton kinase that was approved to treat a common form of leukemia decreases macrophage activity and raises platelets counts in patients with both leukemia and ITP, the drug, called ibrutinib, also inhibits the function of platelets, which reduces its efficacy in ITP.
Scientists have identified a single molecule that may explain how bacteria can trigger one of the most severe types of asthma, a discovery that for the first time identifies the "missing link" between exposure to bacterial components and extreme inflammation of the lungs' airways.
The new research not only clarifies how a severe form of asthma affects patients, but further underscores how bacterial dysbiosis—disruptions in beneficial bacteria amid exposure to pathogenic forms—affects vulnerable lungs. Going into the research, scientists already knew that bacterial molecules can trigger inflammatory activity in the lungs' airways because patients with severe asthma often have changes in their bacterial populations. Yet the exact mechanisms by which bacteria exacerbate asthma remained unclear.
Seeking answers, Dr. Sarah Headland and colleagues in the immunology division of Genentech in south San Francisco, zeroed in on a form of asthma known as non-type-2 to find out why it is one of the severest forms of inflammatory respiratory disease. She and her team have also begun the arduous task of developing a customized therapy.
A University of Illinois at Urbana-Champaign research team has discovered a way to produce a special class of molecule that could open the door for new drugs to treat currently untreatable diseases.
Open the household medicine cabinet and you will likely find organic derivatives of ammonia, called amines. They are one of the most prevalent structures found in medicines today. More than 40 percent of drugs and drug candidates contain amines, and 60 percent of those amines are tertiary, so named for the three carbons that are bonded to a nitrogen.
Tertiary amines are found in some of the most impactful human medicines, including antibiotics, breast cancer and leukemia drugs, opioid pain medications, antihistamines, blood thinners, HIV treatments, antimigraine medications and more. They increase a drug's solubility and can trigger its key biological functions.
