Psychedelics improve mental health, cognition in special ops veterans

The Colorado River toad (Incilius alvarius), also known as the Sonoran Desert toad, is a toad species found in northwestern Mexico and the southwestern United States. It is well known for its ability to exude toxins from glands within its skin that have psychoactive properties.
Photo Credit: Alan Schmierer
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One treatment each of two psychedelic drugs lowered depression and anxiety and improved cognitive functioning in a sample of U.S. special operations forces veterans who sought care at a clinic in Mexico, according to a new analysis of the participants’ charts. 

The treatment included a combination of ibogaine hydrochloride, derived from the West African shrub iboga, and 5-MeO-DMT, a psychedelic substance secreted by the Colorado River toad. Both are designated as Schedule I drugs under the U.S. Controlled Substances Act.

In addition to relieving symptoms of post-traumatic stress disorder (PTSD), the combined treatment also alleviated cognitive impairment linked to traumatic brain injury – which stood out to researchers from The Ohio State University who led the chart-review analysis. Many special operations forces veterans seeking treatment for complex psychiatric symptoms do not respond to more traditional therapies. 

“What sets this group apart from some other veterans and civilians is that often, they are exposed to repeated traumatic events as a routine part of their jobs. This build-up of exposure to these difficulties seems to produce a cluster of challenges that include traumatic brain injury, which we know in and of itself predisposes people to mental health problems,” said lead author Alan Davis, associate professor and director of the Center for Psychedelic Drug Research and Education (CPDRE) in Ohio State’s College of Social Work. 

“So, the fact that we saw that there were improvements in cognitive functioning linked to brain injury were probably the most striking results, because that’s something we didn’t predict and it’s very new and novel in terms of how psychedelics might help in so many different domains.” 

New strategy for eye condition could replace injections with eyedrops

Yulia Komarova, UIC associate professor in the department of pharmacology and regenerative medicine at the College of Medicine
Photo Credit: Komarova

A new compound developed at the University of Illinois Chicago could potentially offer an alternative to injections for the millions of people who suffer from an eye condition that causes blindness.

Wet age-related macular degeneration causes vision loss due to the uncontrolled growth and leakage of blood vessels in the back of the eye. A new paper in Cell Reports Medicine led by UIC researcher Yulia Komarova finds that a small-molecule inhibitor can reverse damage from AMD and promote regenerative and healing processes. 

The drug can also be delivered via eyedrops — an improvement over current treatments for AMD, which require repeated injections into the eye. 

“The idea was to develop something that can be more patient-friendly and doesn’t require a visit to the doctor’s office,” said Komarova, associate professor of pharmacology at the College of Medicine. 

“Anti-tangle” molecule could aid search for new dementia treatments, say scientists

Scientists at Bath have found a way of blocking the protein tangles that are associated with dementia diseases
Photo Credit: NCI

Scientists have identified a molecule that can prevent tangling of a brain protein that is linked to diseases such as Parkinson’s. The findings may provide insights into new ways of treating or diagnosing the early stages of dementia.

Alpha-synuclein, a protein found in brain cells, is commonly associated with neurodegenerative diseases such as Parkinson's, a debilitating neurological disorder affecting millions worldwide.

Like all proteins, it is made up of a long strand of molecules called amino acids. When it’s made, this strand folds in on itself to form a complex but precise 3D shape, made up of sub-structures and loops.

In healthy individuals, alpha-synuclein interacts with cell membranes where it plays a role in how brain cells (neurons) communicate with each other, but as a person ages, the 3D shape of the protein can malformed, or “misfolded”, causing it to start sticking together to form toxic clumps in the brain.

Over time these clumps continue to stack, forming fibers that can interfere with the protein’s normal role, eventually killing brain cells, contributing to the development of Parkinson's and related dementia diseases.

Pharmacy researcher develops intervention for metabolic diseases like diabetes, stroke and heart disease

Photo Credit: Michal Jarmoluk

An investigator with the University of Kansas School of Pharmacy has filed an invention disclosure, part of a provisional patent application with the United States Patent and Trademark Office, for a treatment that could apply to heart disease, stroke and a host of other human diseases related to metabolism.

Liqin Zhao, KU associate professor of pharmacology & toxicology and investigator at the Life Span Institute2, has researched the human ApoE gene for years. A major focus of her work centers on how the ApoE2 variant — one of three major isoforms of ApoE gene — might protect people from Alzheimer’s disease3.

Now, based upon a discovery made during her Alzheimer’s-disease work, Zhao is patenting a way to leverage rhApoE2 to regulate blood lipids. Lipids, like fats and oils, are building materials of life at the cellular level that also are tied to heart disease and other metabolic diseases.

“In essence, we found that rhApoE2 significantly lowered blood levels of a number of ceramides,” Zhao said. “Moreover, rhApoE2 increased blood levels of a variety of ‘good triglycerides’ — triglycerides that contain health-promoting, long-chain polyunsaturated fatty acids such as alpha-linolenic acid, EPA and DHA, and lowered levels of ‘bad triglycerides,’ or triglycerides that contain saturated or monosaturated fatty acids that can impose a cardiovascular risk.”

Elimination of type of bacteria suggests treatment for endometriosis

Fusobacterium (white dots) is highly expressed near the uterus (endometrium) of endometriosis patients.
Image Credit: Professor Yutaka Kondo

A research group from the Graduate School of Medicine and iGCORE at Nagoya University in Japan, has discovered that using an antibiotic to target Fusobacterium reduced the formation of lesions associated with endometriosis, a gynecological disorder characterized by endometrial tissue usually found inside the uterus being found outside it. Their findings suggest an alternative treatment for this disorder. The study was published in Science Translational Medicine.

Endometriosis affects one in ten women between the ages of 15 and 49. The disorder can cause lifelong health problems, including pelvic pain and infertility. Although it can be treated using hormone therapy and surgical resection, these procedures sometimes lead to side effects, recurrence, and a significant impact on pregnancy.

The group led by Professor Kondo (he, him) and Assistant Professor Ayako Muraoka (she, her) from the Nagoya University Graduate School of Medicine, in collaboration with the National Cancer Center, found that the uterus of mice infected with Fusobacterium had more and heavier lesions. However, mice that had been given an antibiotic to eradicate Fusobacterium saw improved lesion formation.

Modified lactic acid bacteria provide faster wound healing

The lactic acid bacteria, or Limosilactobacillus reuteri, is genetically modified to produce the chemokine CXCL12 (ILP100-Topical). 
Photo Credit: Martina Sjaunja

Complicated, hard-to-heal wounds are a growing medical problem and there are currently only two drugs approved with proven efficacy. In a new study on humans, researchers at Uppsala University show that treatment with a specific type of modified lactic acid bacteria works well and has a positive effect on the healing of wounds.

In several controlled preclinical models, the research team behind the new study has previously demonstrated accelerated wound healing after topical treatment (treatment on the skin) using lactic acid bacteria, or Limosilactobacillus reuteri, genetically modified to produce the chemokine CXCL12 (ILP100-Topical).

The researchers can now show data from the first clinical study on humans, in which the main objective was to establish safety and tolerability. Other objectives were to see clinical and biological effects on wound healing using traditionally accepted methods, as well as more exploratory and traceable measurements.

36 healthy volunteers were included in the study with a total of 240 induced wounds studied. The study’s design and methodology are described in more detail below.

New model offers a way to speed up drug discovery

Researchers can screen more than 100 million compounds in a single day — much more than any existing model.
Photo Credit: Myriam Zilles

Huge libraries of drug compounds may hold potential treatments for a variety of diseases, such as cancer or heart disease. Ideally, scientists would like to experimentally test each of these compounds against all possible targets, but doing that kind of screen is prohibitively time-consuming.

In recent years, researchers have begun using computational methods to screen those libraries in hopes of speeding up drug discovery. However, many of those methods also take a long time, as most of them calculate each target protein’s three-dimensional structure from its amino-acid sequence, then use those structures to predict which drug molecules it will interact with.

Researchers at MIT and Tufts University have now devised an alternative computational approach based on a type of artificial intelligence algorithm known as a large language model. These models — one well-known example is ChatGPT — can analyze huge amounts of text and figure out which words (or, in this case, amino acids) are most likely to appear together. The new model, known as ConPLex, can match target proteins with potential drug molecules without having to perform the computationally intensive step of calculating the molecules’ structures.

Scientists closing in on long-lasting swine flu vaccine

 A team led by Eric Weaver, associate professor of biological sciences, has developed a robust vaccine against a strain of swine influenza. Framed by a model of nucleic acid proteins is (from left) Weaver; Matt Pekarek, a graduate student in the Weaver Lab; Cedric Wooledge, a technician with the Institutional Animal Care Program; David Steffen, with the Nebraska Veterinary Diagnostic Center; and Nicholas Jeanjaquet and Erika Petro-Turnquist, both doctoral students in the Weaver Lab. Not pictured is Hiep Vu, assistant professor in the Nebraska Center for Virology and Department of Animal Science.
Photo Credit: Craig Chandler | University Communication and Marketing

A successful long-term experiment with live hogs indicates Nebraska scientists may be another step closer to achieving a safe, long-lasting and potentially universal vaccine against swine flu.

The results are not only important to the pork industry, they hold significant implications for human health. That’s because pigs act as “mixing vessels,” where various swine and bird influenza strains can reconfigure and become transmissible to humans. In fact, the 2009 swine flu pandemic, involving a variant of the H1N1 strain, first emerged in swine before infecting about a fourth of the global population in its first year, causing nearly 12,500 deaths in the United States and perhaps as many as 575,000 worldwide, according to the Centers for Disease Control and Prevention.

“Considering the significant role swine play in the evolution and transmission of potential pandemic strains of influenza and the substantial economic impact of swine flu viruses, it is imperative that efforts be made toward the development of more effective vaccination strategies in vulnerable pig populations,” said Erika Petro-Turnquist, a doctoral student and lead author of the study recently published in Frontiers in Immunology.

Progesterone could protect against Parkinson's

Lennart Stegemann (left) and Paula Neufeld are working on their doctoral theses and were able to celebrate an early success with the top-class publication.
Photo Credit: © RUB, Marquard

In one study, progesterone showed a protective effect on the nerve cells of the intestine. This gives hope for the hormone to be used against Parkinson's.

There is mutual communication between the nerve cells of the gastrointestinal tract and those in the brain and spinal cord. It suggests that the digestive nervous system could affect brain processes that lead to Parkinson's. Paula Neufeld and Lennart Stegemann, who are doing their doctorate in the cytology department of the Medical Faculty of the Ruhr University Bochum, have demonstrated progesterone receptors for the first time in the nerve cells of the gastrointestinal tract and have shown that progesterone protects the cells. Their discovery opens up perspectives for the development of novel neuroprotective therapeutic approaches to counteract diseases such as Parkinson's or Alzheimer's. The study is in the journal Cells.

Researchers develop new method to synthesize cannabis plant compound

Photo Credit: Matthew Brodeur

A group of researchers at Leipzig University has developed a new method for synthesizing cis-tetrahydrocannabinol (THC) – a natural substance found in the cannabis plant that produces the characteristic psychoactive effect and has many potential applications, including in the pharmaceutical industry. “Our strategy makes it possible to produce cis-tetrahydrocannabinoids and test them for their biological activity,” explains researcher Caroline Dorsch, who, together with Professor Christoph Schneider from the Institute of Organic Chemistry, has published her findings in the journal Angewandte Chemie.

She points out that until now there has been no way of synthesizing this structural class in a consistent way. With their simple, inexpensive and nature-based synthesis, the Leipzig researchers have for the first time made the substance class of cis-tetrahydrocannabinoids accessible for a broad range of applications. The researcher notes that because previous methods required many steps and large amounts of chemicals and solvents, their approach is clearly superior. The substance can be synthesized with high overall yields and excellent optical purities using the new method.  

Deficiency causes appetite for meat

A carnivorous leaf of Triphyophyllum peltatum with glands excreting a sticky liquid to capture insect prey.
Photo Credit: Traud Winkelmann / Universität Hannover

Under certain circumstances, a rare tropical plant develops into a carnivore. A research team from the universities of Hannover and Würzburg has now deciphered the mechanism responsible for this.

Triphyophyllum peltatum is a unique plant. Native to the tropics of West Africa, the liana species is of great interest for medical and pharmaceutical research due to its constituents: In the laboratory, this show promising medically useful activities against pancreatic cancer and leukemia cells, among others, as well as against the pathogens that cause malaria and other diseases.

However, the plant species is also interesting from a botanical perspective: Triphyophyllum peltatum is the only known plant in the world that can become a carnivore under certain circumstances. Its menu then includes small insects, which it captures with the help of adhesive traps in the form of secretion drops and digests with synthesized lytic enzymes.

Putting the STING into cancer immunotherapy

Belcher and Hammond Lab researchers developed a cancer vaccine that could make checkpoint blockade therapies more effective for more patients.
Illustration Credit: Bendta Schroeder

Immune checkpoint blockade therapies have been revolutionary in the treatment of some cancer types, emerging as one of the most promising treatments for diseases such as melanoma, colon cancer, and non-small cell lung cancer.  

While in some cases checkpoint blockade therapies elicit a strong immune response that clears tumors, checkpoint inhibitors do not work for all tumor types or all patients. Moreover, some patients who do experience an initial benefit from these therapies see their cancers recur. Only a small minority of patients treated with checkpoint blockade therapies see lasting benefits. Researchers have developed various combination therapy strategies to overcome resistance to checkpoint blockade therapies, with the STING pathway emerging as one of the most attractive lines of inquiry.  

In a study appearing in Advanced Healthcare Materials, a team of MIT researchers engineered a therapeutic cancer vaccine capable of restoring STING signaling and eliminating the majority of tumors in mouse models of colon cancer and melanoma, with minimal side effects. The vaccine also inhibited metastasis in a breast cancer mouse model and prevented the recurrence of tumors in cured mice. 

Fecal beads to act at the core of the intestinal microbiota

Alginate microparticles containing isolated bacterial strains (white particles) and a fecal transplant (brown particles), with a zoom on the structure of the microparticles by scanning electron microscopy.
 Image Credits: © Adèle Rakotonirina et Nathalie Boulens
(CC BY-NC-ND 4.0)

A UNIGE team, in collaboration with the CHUV, has developed a new method of encapsulating fecal bacteria to treat a serious intestinal infection.

Clostridioides difficile infection causes severe diarrhea and results in the death of nearly 20,000 patients in Europe each year. It is one of the most common hospital-acquired infections. When it relapses, the disease must be treated by fecal microbiota transplantation. This treatment, which is administered via a nasogastric or colorectal tube, is very demanding. Researchers at the University of Geneva (UNIGE), in collaboration with the Lausanne University Hospital (CHUV), have developed small beads to be taken orally, which could radically improve its administration. This work can be found in the International Journal of Pharmaceutics.

Naturally found in 15% of the population, Clostridioides difficile is a bacterium that can become pathogenic when the protective "barriers" of our intestinal flora are weakened. This is particularly the case after prolonged and repeated use of antibiotics. Clostridioides difficile then causes severe diarrhea and can lead to a critical inflammation of the colon, known as pseudomembranous colitis. With more than 124,000 cases per year in Europe, it is one of the most common hospital-acquired infections and is fatal in about 15% of cases.

Efficient synthesis of indole derivatives, an important component of most drugs, allows the development of new drug candidates

Efficient synthesis of indole derivatives, an important component of most drugs,  allows the development of new drug candidates. 
Illustration Credit: Reiko Matsushita

A research group at Nagoya University in Japan has successfully developed an ultrafast and simple synthetic method for producing indole derivatives. Their findings are expected to make drug production more efficient and increase the range of potential indole-based pharmaceuticals to treat a variety of diseases. Their findings were published in Communications Chemistry. 

An indole is an organic compound consisting of a benzene ring and a pyrrole ring. Heteroatom alkylation at the carbon atom next to the indole ring is particularly useful to create a wide range of new indole derivatives and many anti-inflammatory, anticancer, and antimicrobial treatments contain them.

In the past, this heteroatom alkylation has proven difficult because indoles easily and rapidly undergo unwanted dimerization/multimerization, processes in which two or more molecules combine during the reaction to form unwanted larger molecules. These unwanted by-products limit the yield of the desired product.  

Scientists Identify Antivirals that Could Combat Emerging Infectious Diseases

Aedes aegypti mosquito.
Photo Credit: Pixabay

A new study has identified potential broad-spectrum antiviral agents that can target multiple families of RNA viruses that continue to pose a significant threat for future pandemics. The study, led by Gustavo Garcia Jr. in the UCLA Department of Molecular and Medical Pharmacology, tested a library of innate immune agonists that work by targeting pathogen recognition receptors, and found several agents that showed promise, including one that exhibited potent antiviral activity against members of RNA viral families.

The ongoing SARS-CoV-2 pandemic, which has claimed nearly seven million lives globally since it began, has revealed the vulnerabilities of human society to a large-scale outbreak from emerging pathogens. While accurately predicting what will trigger the next pandemic, the authors say recent epidemics as well as global climate change and the continuously evolving nature of the RNA genome indicate that arboviruses, viruses spread by arthropods such as mosquitoes, are prime candidates. These include such as Chikungunya virus (CHIKV), Dengue virus, West Nile virus and Zika virus. The researchers write: “Given their already-demonstrated epidemic potential, finding effective broad-spectrum treatments against these viruses is of the utmost importance as they become potential agents for pandemics.”

In their new study, published in Cell Reports Medicine, researchers found that several antivirals inhibited these arboviruses to varying degrees. “The most potent and broad-spectrum antiviral agents identified in the study were cyclic dinucleotide (CDN) STING agonists, which also hold promise in triggering an immune defense against cancer,” said senior author Vaithi Arumugaswami, Associate Professor in the UCLA Department of Molecular and Medical Pharmacology and a member of the California NanoSystems Institute.

Drug for rare form of ALS approved by FDA

A new drug has been approved by the Food and Drug Administration (FDA) for a rare, inherited form of amyotrophic lateral sclerosis (ALS). Called tofersen, the drug — developed by Biogen Inc. and based in part on research conducted at Washington University School of Medicine in St. Louis — slows the progression of the deadly, paralyzing disease. 

Video Credit: Huy Mach and Tamara Bhandari

A new drug has been approved by the Food and Drug Administration (FDA) for a rare, inherited form of amyotrophic lateral sclerosis (ALS), a paralyzing neurological disease. Known as tofersen, the drug has been shown to slow progression of the deadly disease. International clinical trials of tofersen, developed by the global biotechnology company Biogen Inc., were led by a neurologist at Washington University School of Medicine in St. Louis.

Tofersen, also known by the brand name Qalsody, is designed for ALS patients whose disease is caused by mutations in the gene SOD1. In the phase 3 clinical trial, the drug reduced molecular signs of disease and curbed neurodegeneration in the first six months of use. Over longer time frames, some participants experienced a stabilization of muscle strength and control.

The drug is approved under the accelerated approval pathway, under which FDA may approve drugs for serious conditions where there is an unmet medical need and a drug is shown to have an effect on a surrogate endpoint that is reasonably likely to predict a clinical benefit to patients.

Durable, low-cost COVID-19 vaccine could help fill in gaps around the world

A protein-based COVID-19 vaccine developed by researchers at Stanford Medicine and their colleagues may be ideal for infants.
Image Credit: Gerd Altmann

In a study led by Stanford Medicine researchers, a low-cost COVID-19 vaccine that does not require refrigeration provided immunity in rhesus monkeys for one year.

A low-cost, protein-based COVID-19 vaccine tested in rhesus monkeys by Stanford Medicine researchers and colleagues offered immunity against known variants for at least one year. Researchers hope the vaccine, which can remain unrefrigerated for up to two weeks and may be especially beneficial for infants, will help alleviate the need for boosters while improving herd immunity around the world.

If the vaccine succeeds in human trials, it could be an alternative to the mRNA vaccines widely used for COVID-19, without drawbacks such as high expense and low-temperature storage requirements. Protein-based vaccines, which use protein fragments of the target virus rather than the whole virus, have been used for decades to protect against diseases such as shingles and hepatitis.

“Our motivation was to come up with a vaccine that would provide worldwide access to vaccination,” said Peter Kim, PhD, the Virginia and D.K. Ludwig Professor in Biochemistry. “In the case of the mRNA vaccines, for example, they are expensive, difficult to make and require storage in freezers. So, we wanted to solve those problems with this vaccine.”

Revealed: Molecular “superpower” of antibiotic-resistant bacteria

Scanning electron micrograph of en:Clostridioides difficile bacteria from a stool sample
Photo Credit: Public Health Image Library

A species of ordinary gut bacteria that we all carry flourishes when the intestinal flora is knocked out by a course of antibiotics. Since the bacteria is naturally resistant to many antibiotics, it causes problems, particularly in healthcare settings. A study led from Lund University in Sweden now shows how two molecular mechanisms can work together make the bacterium extra resistant. “Using this knowledge, we hope to be able to design even better medicines,” says Vasili Hauryliuk, senior lecturer at Lund University, who led the study.

The threat from antibiotic resistant bacteria is as well-known as it is grave. Last year, The Lancet reported that an estimated 1.27 million people died in 2019 as a result of bacterial infection that could not be treated with existing medicines. To tackle this threat is it is essential to understand the underpinning molecular mechanisms.

Protein domain common to plants and animals plays role in COVID-19 infection

ORNL scientists mutated amino acids in a receptor protein, shown in green, which diminished interaction with the SARS-CoV-2 virus spike protein, shown in red. Mutating the receptor protein hampered the virus’s ability to infect host cells.
Image Credit: ORNL, U.S. Dept. of Energy

Oak Ridge National Laboratory scientists exploring bioenergy plant genetics have made a surprising discovery: a protein domain that could lead to new COVID-19 treatments.

Researchers found the same plasminogen-apple-nematode, or PAN, domain studied by ORNL in plants like poplar and willow is also present in the human NRP1 receptor protein. NRP1 is less studied than the ACE-2 receptor targeted by current COVID-19 treatments, but this research shows its promise as a future therapeutic target.

By mutating amino acids called cysteine residues in the PAN domain of NRP1, researchers disrupted the ability of the SARS-CoV-2 virus to use its spike protein to invade cells, as described in iScience. ORNL scientists have also linked PAN to the growth of cancerous tumors.

Drug form of traditional Chinese medicine compound improved survival of mice with brain tumors

Indirubin is a natural product present in indigo plants and the active ingredient of the traditional Chinese medicine Dang Gui Long Hui Wan, which is used to treat chronic diseases.
Photo Credit: Courtesy of Brown University

A new study shows how a drug made from a natural compound used in traditional Chinese medicine works against malignant brain tumors in mice, creating a promising avenue of research for glioblastoma treatment.

In the study, published in Cell Reports Medicine, researchers showed how a formulation of the compound, called indirubin, improved the survival of mice with malignant brain tumors. They also tested a new formulation that was easier to administer, taking the potential pharmaceutical approach one step closer to clinical trials with human participants.  

“The interesting thing about this drug is that it targets a number of important hallmarks of the disease,” said Sean Lawler, lead author, associate professor of pathology and laboratory medicine, and researcher at the Legorreta Cancer Center of Brown University. “That's appealing because this type of cancer keeps finding ways around individual mechanisms of attack. So, if we use multiple mechanisms of attack at once, perhaps that will be more successful.”