Category: New Compounds and Treatments

Controlling Allergic Asthma without Compromising Flu Resistance

Young girl sneezing
Photo by Andrea Piacquadio on Unsplash

Blocking calcium signalling in immune cells suppresses allergic asthma, but without compromising the immune defence against flu viruses, according to the findings of a new study published in Science Advances.

The researchers showed that, in a mouse model, removing the gene for a certain calcium channel reduced asthmatic lung inflammation caused by house dust mite faeces, a common cause of allergic asthma. Blocking signals sent through this channel, the calcium release-activated calcium (CRAC) channel, with an investigational inhibitor drug had a similar effect.

The study revolved human cells’ use of signalling and switch-flipping ions, mainly calcium. When triggered by viral proteins or allergens, T cells open channels in their outer membranes, allowing calcium in to activate signalling pathways that control cell division and secretion of cytokine molecules.

Past work had found that CRAC channels in T cells regulate their ability to multiply into armies of cells designed to fight infections caused by viruses and other pathogens.

The new study showed that the CRAC channel inhibitor reduced allergic asthma and mucus build-up in mice without undermining their immune system’s ability to fight influenza, a main worry of researchers seeking to tailor immune-suppressing drugs for several applications.

“Our study provides evidence that a new class of drugs that target CRAC channels can be used safely to counter allergic asthma without creating vulnerability to infections,” said senior study author Stefan Feske, MD, a professor at NYU Langone Health. “Systemic application of a CRAC channel blocker specifically suppressed airway inflammation in response to allergen exposure.”

Allergic asthma, which is the most common form of the disease, is characterised by increased type 2 (T2) inflammation, which involves T helper (Th) 2 cells, the study authors noted. Th2 cells produce cytokines that play important roles in both normal immune defences, and in disease-causing inflammation that occurs in the wrong place and amount. In allergic asthma, cytokines promote the production of IgE antibodies and the recruitment to the lungs of inflammation-causing immune cells called eosinophils, the hallmarks of the disease.

In the new study, the research team found that deletion of the ORAI1 protein in T cells, which makes up the CRAC channel, or treating mice with the CRAC channel inhibitor CM4620, thoroughly suppressed Th2-driven airway inflammation in response to house dust mite allergens.

Treatment with CM4620 significantly reduced airway inflammation when compared to an inactive control substance, with the treated mice also showing much lower levels of Th2 cytokines and related gene expression. Without calcium entering through CRAC channels, T cells are unable to become Th2 cells and produce the cytokines that cause allergic asthma, the authors say.

Conversely, ORAI1 gene deletion, or interfering with CRAC channel function in T cells via the study drug, did not hinder T cell-driven antiviral immunity, as lung inflammation and immune responses were similar in mice with and without ORAI1.

“Our work demonstrates that Th2 cell-mediated airway inflammation is more dependent on CRAC channels than T cell-mediated antiviral immunity in the lung,” said study co-first author Yin-Hu Wang, PhD. “This suggests CRAC channel inhibition as a promising, potential future treatment approach for allergic airway disease.”

Source: NYU Langone Health via PRNewsWire

Harnessing Metals to Fight Fungal Infections

Source: NCI

Even as new, drug-resistant fungal strains are being detected, the development of new antifungal drugs has reached a virtual standstill in recent years. Today, only around a dozen clinical trials are underway with new active agents for the treatment of fungal infections. A new drug discovery effort, reported in JACS Au, has identified a range of metal compounds that are highly effective as antifungals, but mistrust around using metals in drugs remains.

“In comparison with more than a thousand cancer drugs that are currently being tested on human subjects, this is an exceptionally small number,” explains Dr Angelo Frei of the Department of Chemistry, Biochemistry and Pharmacy at the University of Bern, lead author of the study.

To encourage the development of anti-fungal and antibacterial agents, researchers at the University of Queensland in Australia have founded the Community for Open Antimicrobial Drug Discovery, or CO-ADD. The ambitious goal of the initiative is to find new antimicrobial active agents by offering chemists worldwide the opportunity to test any chemical compound against bacteria and fungi at no cost. As Frei explains, the initial focus of CO-ADD has been on “organic” molecules, which mainly consist of the elements of carbon, hydrogen, oxygen and nitrogen, and do not contain any metals.

However, Frei, who is trying to develop new metal-based antibiotics with his research group at the University of Bern, has found that over 1000 of the more than 300 000 compounds tested by CO-ADD contained metals. “For most folks, when used in connection with the word ‘people’, the word metal triggers a feeling of unease. The opinion that metals are fundamentally harmful to us is widespread. However, this is only partially true. The decisive factor is which metal is used and in which form,” explains Frei, who is responsible for all the metal compounds in the CO-ADD database.

In their new study, the researchers turned their attention to the metal compounds which showed activity against fungal infections. Here, 21 highly-active metal compounds were tested against various resistant fungal strains. These contained the metals cobalt, nickel, rhodium, palladium, silver, europium, iridium, platinum, molybdenum and gold. “Many of the metal compounds demonstrated a good activity against all fungal strains and were up to 30 000 times more active against fungi than against human cells,” explains Frei. The most active compounds were then tested in a model organism, the larvae of the wax moth. The researchers observed that just one of the eleven tested metal compounds showed signs of toxicity, while the others were well tolerated by the larvae. In the next step, some metal compounds were tested in an infection model, and one compound was effective in reducing the fungal infection in larvae.

Considerable potential for broad application

Metal compounds are not new to the world of medicine: Cisplatin, for example, which contains platinum, is one of the most widely used anti-cancer drugs. Despite this, there is a long way to go before new antimicrobial drugs that contain metals can be approved. “Our hope is that our work will improve the reputation of metals in medical applications and motivate other research groups to further explore this large but relatively unexplored field,” says Frei. “If we exploit the full potential of the periodic table, we may be able to prevent a future where we don’t have any effective antibiotics and active agents to prevent and treat fungal infections.”

Source: University of Bern

Promising New Lupus Pill Reverses Organ Damage in Mice

The autoimmune disease lupus has no cure, and current treatment is limited in its effectiveness in reducing symptoms and controlling damage to the body. Now, scientists report they have begun phase 2 clinical trials with a compound that, in mice, not only prevents lupus-like symptoms, but also reverses signs of organ damage caused by the disease and prevents death.

“Few new therapies have succeeded, but we believe our compound could be an effective treatment for lupus,” says Alaric Dyckman, PhD. The disease affects 5 million people worldwide, according to the Lupus Foundation of America. Symptoms include rashes, extreme fatigue, pain, inflammation and deterioration of organs, such as the kidneys and heart, which can lead to death.

The researchers will present their results at the fall meeting of the American Chemical Society (ACS). ACS Fall 2022 is a hybrid meeting being held virtually and in-person Aug. 21–25, with on-demand access available Aug. 26–Sept. 9.

Lupus develops when the immune system attacks the body’s tissues. Years ago, researchers began suspecting that this process involved toll-like receptors (TLRs) 7 and 8, which are cellular proteins that activate the immune system when they detect viral RNA or mistakenly identify a person’s own RNA as a threat.

“Genetic data and evaluations of injectable treatments suggested TLR7 and 8 could be drug targets for lupus. What was missing was an ability to directly block these receptors with small molecules that could be taken orally,” explained Dr Dyckman. So in 2010, he and other scientists at Bristol Myers Squibb (BMS) set out to develop such compounds.

New options would be welcome, since many patients don’t respond fully to current medications. The two approved therapies that were specifically developed for lupus reduce activity of specific immune system components: AstraZeneca’s anifrolumab blocks an interferon receptor, while GlaxoSmithKline’s belimumab reduces the survival of B cells. Other treatments include steroids and other general immune suppressants, anti-malarials, anti-inflammatories and anticoagulants. However, anifrolumab and belimumab must be given by injection or infusion, Dr Dyckman noted, while steroids and general immune suppressants are associated with safety concerns and were not originally designed to treat lupus.

The BMS researchers started by screening the company’s compound collection for molecules that could block TLR7/8 signalling. The team refined the search further to improve interaction with other receptors, and potency, and enablee oral dosing. The resulting compound, afimetoran, binds to the target TLRs, inhibiting their operation to achieve beneficial activity. Like anifrolumab, it interferes with interferon, and like belimumab, it controls damage from overactive B cells. It also inhibits the production of multiple proinflammatory cytokines that cause a lot of tissue damage in lupus.

“With afimetoran, not only could we prevent the development of lupus-like symptoms in mice before their disease onset, but we could actually reverse the symptoms and prevent death in animals that were days or weeks away from succumbing to the disease,” Dr Dyckman said. “We hadn’t seen that reversal with other mechanisms we had evaluated, so we were particularly excited about that finding.” Dr Dyckman said that he believes afimetoran effects together may let it control lupus as well as or better than existing treatments, doing it through an oral route.

Afimetoran also combined well with corticosteroid treatments in mice, so patients might be able to use lower doses of steroids and reducing associated side effects.

Phase 1 clinical trials of afimetoran have been completed. The trials showed that a low, once-daily oral dose was safe in healthy patients and could almost completely block signalling through TLR7/8. And now, a phase 2 trial to test its effectiveness in lupus patients is underway. Because of its mode of action, Dr Dyckman said, it may also work in other autoimmune disorders, such as psoriasis or arthritis.

BMS is testing other compounds against lupus, such as deucravacitinib, an oral, selective tyrosine kinase 2 (TYK2) inhibitor that is moving into phase 3 studies. Other companies are also making progress. Merck, for instance, is evaluating its own oral TLR7/8 blocker, enpatoran, in phase 2 trials.

Despite intensive efforts to develop new therapies over the past several decades, few have succeeded. “So getting a lot of shots on goal is important,” Dr Dyckman said. “Also, lupus is such a heterogeneous disease that it’s unlikely that any single approach will provide relief for all of the patients out there.”

Source: EurekAlert!

A Novel Anticoagulant That can be ‘Deactivated’

Source: NCI

A new biomolecular anticoagulant platform reported in Nano Letters holds promise as a revolutionary advancement over the anticoagulants currently used during surgeries and other procedures. The technology is based around injectable fibre structures which can be quickly dissolved and excreted by the kidneys.

“We envision the uses of our new anticoagulant platform would be during coronary artery bypass surgeries, kidney dialysis, and a variety of vascular, surgical and coronary interventions,” said Kirill Afonin, leader of the team which invented the technology. “We are now investigating if there are potential future applications with cancer treatments to prevent metastasis and also in addressing the needs of malaria, which can cause coagulation issues.”

The team’s technology turns to programmable RNA-DNA anticoagulant fibres that, when injected into the bloodstream, form into modular structures that communicate with thrombin. The technology allows the structures to prevent blood clotting as it is needed and then be quickly eliminated via the renal system once their job is done.

The fibre structures use aptamers, short sequences of DNA or RNA designed to specifically bind and inactivate thrombin.

“Instead of having a single small molecule that deactivates thrombin,” Afonin said, “we now have a relatively large structure that has hundreds of the aptamers on its surface that can bind to thrombin and deactivate them. And because the structure becomes larger, it will circulate in the bloodstream for a significantly longer time than traditional options.”

The extended circulation in the bloodstream allows for a single injection, instead of multiple doses. The design also decreases the concentration of anticoagulants in the blood, resulting in less stress on the body’s renal and other systems, Afonin said.

This technology also introduces a novel “kill-switch” mechanism, which reverses the fibre structure’s anticoagulant function with a second injection. This lets makes the fibres able to be metabolised into materials that are tiny, harmless, inactive and easily excreted by the renal system.

The entire process takes place outside the cell, through extracellular communication with the thrombin. The researchers note that this is important as immunological reactions do not appear to occur, based on their extensive studies.

The team has tested and validated the platform in computer models, human blood and various animal models“We conducted proof-of-concept studies using freshly collected human blood from donors in the US and in Brazil to address a potential inter donor variability,” Afonin said.

The technology may provide a foundation for other biomedical applications that require communication via the extracellular environment in patients, he said. “Thrombin is just one potential application,” he said. “Whatever you want to deactivate extracellularly, without entering the cells, we believe you can. That potentially means that any blood protein, any cell surface receptors, maybe antibodies and toxins, are possible.”

The technique permits the design of structures of any shape desired, with the kill switch mechanism intact. “By changing the shape, we can have them go into different parts of the body, so we can change the distribution,” Afonin said. “It gets an extra layer of sophistication of what it can do.”

While the application is sophisticated, production of the structures is relatively easy. “The shelf life is amazingly good for these formulations,” Afonin said. “They’re very stable, so you can dry them, and we anticipate they will stay for years at ambient temperatures, which makes them very accessible to economically challenged areas of the world.”

Source: University of North Carolina

A Potent New Non-opioid Analgesic

Woman using lab equipment
Source: NCI on Unsplash

Researchers co-led by University of Warwick have discovered a potent new non-opioid analgesic with potentially fewer side effects compared to other potent painkillers.

Their study found that a compound called BnOCPA (benzyloxy-cyclopentyladenosine), is a potent and selective analgesic which is non-addictive. BnOCPA also has a unique mode of action and potentially opens a new pipeline for the development of new analgesic drugs.

The research is published in Nature Communications.

Chronic pain has a negative impact on quality of life and many commonly prescribed analgesics come with side effects. Opioid drugs, such as morphine and oxycodone, can lead to addiction and are dangerous in overdose.

Drugs that act on G protein-coupled receptors (GPCRs) are one possibility, but their development is hampered by the propensity of GPCRs to couple to multiple intracellular signalling pathways. A unique feature of BnOCPA is that it only activates one type of GPCR, leading to very selective effects and thus reducing potential side effects.

University of Warwick’s Dr Mark Wall, who led the research said: “The selectivity and potency of BnOCPA make it truly unique and we hope that with further research it will be possible to generate potent painkillers to help patients cope with chronic pain.”

Source: University of Warwick

Two New Antibody Treatments for Crohn’s Disease Equally Effective

Anatomy of the gut
Source: Pixabay CC0

In a clinical trial, two new antibody treatments for Crohn’s disease were approximately similar in effectiveness, according to findings published in The Lancet.

This allows clinicians and patients to make treatment choices based on tolerance, according to Stephen Hanauer, MD, the Clifford Joseph Barborka Professor and a co-author of the study.

“The safety and efficacy of two agents with different mechanisms of action appears to be quite comparable over one year,” said Prof Hanauer.

Crohn’s disease (CD) is a chronic, progressive inflammatory bowel disease, causing abdominal pain, weight loss and fatigue. Treatment has usually focused on alleviating symptoms to achieve clinical remission using corticosteroids or immunomodulators, but more effective treatment is still needed, according to Prof Hanauer.

‘While there are numerous therapies and mechanisms of action for drugs approved for moderate-severe Crohn’s disease there has been a therapeutic ceiling as far as outcomes are concerned, with usually less than 50% of patients in long-term remission,” Prof Hanauer explained.

Recently, several biologic agents have been approved for use. Adalimumab is a monoclonal antibody that reduces inflammatory cytokines by inhibiting tumor necrosis factor alpha. Ustekinumab is another monoclonal antibody, though the drug targets a different set of proteins: interleukin (IL) 12 and IL-23.

Researchers recruited with Crohn’s disease, randomising 191 to receive ustekinumab and 195 to adalimumab. Patients reaching clinical remission were similar between both groups: 65% of 191 patients in the ustekinumab group versus 61% of 195 in the adalimumab group. There were no deaths through one year of study, though slightly more patients in the ustekinumab group discontinued study treatment. Disease severity measures decreased similarly over the study.

Both treatment regimens resulted in clinical remission with similar toxicity profiles.

“There are numerous options for patients with moderate-severe disease. However, the key is to treat patients with an effective regimen and treat to targets as early in the course as possible since we do not have any drugs that impact on fibrosis once it occurs,” Prof Hanauer said.

Source: Northwestern University

Cancer Drug Candidate Spurs Nerve Regeneration

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A candidate cancer drug currently in development has been also shown to stimulate regeneration of damaged nerves after spinal trauma. Four weeks after spinal cord injury, animals treated with the candidate drug, AZD1390, were “indistinguishable” from uninjured animals, according to the researchers.

The study, published in Clinical and Translational Medicine, demonstrated in cell and animal models that the candidate drug, AZD1390, can block the response to DNA damage in nerve cells and promote regeneration of damaged nerves. This restored sensory and motor function after spinal injury.

The announcement comes weeks after the same research team showed a different investigational drug, AZD1236, can reduce damage after spinal cord injury, by blocking the inflammatory response.

AZD1390 is also under investigation by AstraZeneca to block ATM-dependent signalling and repair of DNA double strand breaks (DSBs), an action which sensitises cancer cells to radiation treatment. The ATM protein kinase pathway – a critical biochemical pathway regulating the response to DNA damage. The DNA Damage Response system (DDR) is activated by DNA damage, including DSBs in the genome, which also happen in several common cancers and also after spinal cord injury.

Professor Zubair Ahmed, from the University’s Institute of Inflammation and Ageing and Dr Richard Tuxworth from the Institute of Cancer and Genomic Sciences hypothesised the persistent activation of this system may prevent recovery from spinal cord injury, and that blocking it would promote nerve repair and restore function after injury.

Their initial studies found that AZD1390 stimulated nerve cell growth in culture, and inhibited the ATM protein kinase pathway – a critical biochemical pathway regulating the response to DNA damage.

AZD1390 was tested in animal models following spinal cord injury. Oral treatment with AZD1390 significantly suppressed the ATM protein kinase pathway, stimulated nerve regeneration beyond the site of injury, and improved the ability of these nerves to carry electrical signals across the injury site.

Professor Ahmed commented: “This is an exciting time in spinal cord injury research with several different investigational drugs being identified as potential therapies for spinal cord injury. We are particularly excited about AZD1390 which can be taken orally and reaches the site of injury in sufficient quantities to promote nerve regeneration and restore lost function.

“Our findings show a remarkable recovery of sensory and motor functions, and AZD1390-treated animals being indistinguishable from uninjured animals within 4 weeks of injury.”

Dr Tuxworth added: “This early study shows that AZD1390 could be used as a therapy in life-changing conditions. In addition, repurposing this existing investigational drug potentially means we can reach the clinic significantly faster than developing a new drug from scratch.”

Source: University of Birmingham

The Search for New Cancer Therapies Strikes Gold

Photo by Jingming Pan on Unsplash

The gold complex auranofin has traditionally been used for treating rheumatism but is also being evaluated as a one number of new cancer therapies. According to a study published in Redox Biology, molecules with the same inhibition effect have been discovered that have a more specific effect than auranofin and therefore may have greater potential as cancer therapies.

Auranofin (AF) is classed by the WHO (World Health Organization) as an anti-rheumatic agent and is an active component in the drug Ridaura. AF is also currently being assayed in a string of clinical trials as a possible cancer therapy. One reason for the researchers’ interest in AF is its ability to inhibit thioredoxin reductase (TrxR), a protein central to the thioredoxin system, which protects cells from oxidative stress in all mammals. 

However, TrxR also protects cancer cells, making cancer therapies less effective. Moreover, TrxR, which affects cellular growth and survival, is upregulated in certain forms of cancer.

“There’s a great deal of interest in the ability to inhibit the thioredoxin system in the treatment of cancer, but there’s a risk that healthy cells will also be damaged and killed,” says the study’s co-last author Elias Arnér, professor at the Department of Medical Biochemistry and Biophysics at Karolinska Institutet. “Our aim is for TrxR inhibitors to be as specific as possible.”

The researchers studied the effects of AF in mouse cancer cells (lung adenocarcinoma and melanoma) and compared them with other recently-developed TrxR-inhibiting molecules called TRi-1 and TRi-2 (thioredoxin reductase inhibitors 1 and 2). 

The study, which was based on new proteomic methods of analysing the entire set of proteins in cells, suggests that the TRi compounds are more specific in their effect than AF. The results show that AF causes very high levels of oxidative stress and has other effects that seem unrelated to the inhibition of TrxR. They also demonstrate that TRi-1 seems to be the most specific TrxR inhibitor so far.

“Our results can serve as an important blueprint for further studies of AF’s mechanism of action and side effects,” said the study’s other co-last author Roman Zubarev, professor at the Department of Medical Biochemistry and Biophysics, Karolinska Institutet. “Having now compared AF with the more specific molecules TRi-1 and TRi-2, we hope that our findings will contribute to the further development of TrxR inhibitors as anticancer drugs.”

Source: Karolinska Insitutet

New Antibacterial Molecules Identified

Source: National Cancer Institute on Unsplash

Researchers have identified a new group of molecules with an antibacterial effect against many antibiotic-resistant bacteria. Since the properties of the molecules can easily be altered chemically, the hope is to develop new, effective antibiotics with few side effects. The study appears in PNAS.

Increasing antibiotic resistance is a great concern as few new antibiotics have been developed in the past 50 years.

Most antibiotics work by inhibiting the bacteria’s ability to form a protective cell wall, causing the bacteria to crack (cell lysis). Besides the well-known penicillin, which inhibits enzymes building up the wall, newer antibiotics such as daptomycin or the recently discovered teixobactin bind to a special molecule, lipid II. All bacteria need lipid II as a building block for the cell wall. Antibiotics that bind to Lipid II are usually very large and complex molecules and therefore more difficult to improve with chemical methods. These molecules are in addition mostly inactive against a group of problematic bacteria, which are surrounded by an additional layer, the outer membrane, that hinders penetration of these antibacterials.

“Lipid II is a very attractive target for new antibiotics. We have identified the first small antibacterial compounds that work by binding to this lipid molecule, and in our study, we found no resistant bacterial mutants, which is very promising,” says Birgitta Henriques Normark, professor at the Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, and one of the article’s three corresponding authors.

For this study, published in PNAS, researchers tested a large number of chemical compounds for their ability to lyse pneumococci – the most common cause of community-acquired pneumonia. After a careful follow-up of active compounds from this screening, the researchers found that a group of molecules called THCz inhibits the formation of the cell wall of the bacterium by binding to lipid II. The molecules could also prevent the formation of the sugar capsule that pneumococci need to escape the immune system and to cause disease.

Small molecules offer several benefits, noted Fredrik Almqvist, professor at Umeå University and one of the corresponding authors: “The advantage of small molecules like these is that they are more easy to change chemically. We hope to be able to change THCz so that the antibacterial effect increases and any negative effects on human cells decrease.”

Laboratory work with THCz showed it has an antibacterial effect against many antibiotic-resistant bacteria, such as methicillin-resistant staphylococci (MRSA), vancomycin-resistant enterococci (VRE), and penicillin-resistant pneumococci (PNSP). An antibacterial effect was also found against gonococci, which causes gonorrhoea, and mycobacteria, bacteria that can cause severe diseases such as tuberculosis in humans. None of the bacteria managed to develop resistance to THCz in a laboratory environment.

“We will now also initiate attempts to change the THCz molecule, allowing it to penetrate the outer cell membrane found in some, especially intractable, multi-resistant bacteria,” says Tanja Schneider, professor at the Institute of Pharmaceutical Microbiology at the University of Bonn and one of the corresponding authors.

Source: Karolinska Institutet

Native American Plant Remedies Found to Have Dual Properties

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Following a functional screen of extracts from US plants researchers found that plants with a long history of use by Native Americans as topical analgesics were often also used as gastrointestinal aids.

The study, published today in Frontiers in Physiology, found forest plants that activated the KCNQ2/3 potassium channel, a protein that passes electrical impulses in the brain and other tissues, showed a long history of use by Native Americans as topical analgesics, to treat conditions such as insect bites, stings, sores and burns. Less intuitively, the same plants that activated KCNQ2/3 and were used as traditional painkillers were often also used as gastrointestinal aids, especially for preventing diarrhoea.

“Done in collaboration with the US National Parks Service, this study illustrates how much there is still to learn from the medicinal practices of Native Americans, and how, by applying molecular mechanistic approaches we can highlight their ingenuity, provide molecular rationalizations for their specific uses of plants, and potentially uncover new medicines from plants,” said UCI School of Medicine professor Geoffrey Abbott, PhD.
KCNQ2/3 is present in nerve cells that sense pain, and activating it would relieve pain by reducing pain signal transmission. The breakthrough \came when the team discovered that the same plant extracts that activate KCNQ2/3 have an opposite effect on the related intestinal potassium channel, KCNQ1-KCNE3. Previous studies on modern medicines showed that KCNQ1-KCNE3 inhibitors can prevent diarrhoea.

The Abbott Lab is currently screening native US plants, having shown already that quercetin and tannic and gallic acids explained many of the beneficial effects of the plants. The team also identified binding sites on the channel proteins that produce the effects.

Knowing that these compounds activate versus inhibit closely related human ion channel proteins, drug specificity and safety can be improved and therefore safety. More specifically, the plant compounds can be further optimised with the goal of treating pain and secretory diarrhoea.

“I personally am very excited about the paper; it was my lab’s first published collaboration with the National Park Service, and it shines a light on the incredible ingenuity and medicinal wisdom of Californian Native American tribes,” said Prof Abbott.

New analgesics are being sought to fight the opioid crisis. In addition, according to the CDC, diarrhoeal diseases account for 1 in 9 child deaths worldwide; incredibly, diarrhoea kills over 2000 children every day worldwide – more than AIDS, malaria and measles combined.

Source: University of California – Irvine