Month: May 2023

Categories : CancerTags :

Osteoporosis Drug Zolendronate Could also Help Fight Breast Cancer

On By ModernMedia
Killer T cells about to destroy a cancer cell.

Triple-negative breast cancer (TNBC) is the most aggressive and deadly form of breast cancer with limited treatment options and a high probability of recurrence. Researchers from the University of Frieburg discovered that coordinated differentiation and changes in the metabolism of breast cancer stem cells make them invisible for the immune system. Counteracting the metabolic change with the drug zolendronate could make immunotherapy using gamma delta T cells more efficient against TNBC. The research team was led by Prof Dr Susana Minguet and published in Cancer Immunology Research.

TNBC cells hide from gamma delta T cells

Gamma delta T cells recognise and kill cells that produce stress-induced molecules and phosphoantigens, a common characteristic of cancer cells. Because gamma delta T cells work differently to other types of T cells, they are being investigated as an alternative to existing immunotherapies. In the current study, the researchers tested the effect of gamma delta T cells on TNBC using isolated cancer cells and a recently developed mouse model that closely replicates the tumour properties found in human patients.

While the gamma delta T cells worked well against isolated breast cancer stem cells from patients, they had a much weaker effect in the mouse model. This was due to adaptations of the cancer cells that let them stay unnoticed by the immune system, the researchers found. These adaptations included the downregulation of the so-called mevalonate pathway: a metabolic pathway that leads to the production of phosphoantigens – one of the classes of molecules that gamma T cells recognise. This escape mechanism likely also happens in patients with TNBC: analysis of public patient databases showed that reduced expression of key molecules of the mevalonate pathway correlate with a worse prognosis.

The immune evasion of TNBC cells is reversible

This newly discovered escape mechanism can be counteracted by the drug zolendronate, which is FDA-approved for the treatment of osteoporosis and bone metastasis. When the researchers treated the escapist cells with zolendronate, the gamma T cells became a lot more efficient in clearing the cancer. “Our findings explain why current clinical trials using gamma delta T cells are not resulting in the expected success,” Minguet summarises. “We found a possible pharmacological-based approach to revert immune escape, which paves the way for novel combinatorial immunotherapies for triple negative breast cancer.”

Source: University of Freiburg

Categories : Ageing Diet and NutritionTags :

Can Low-carbohydrate or Low-fat Diets Extend Lifespan?

On By ModernMedia

Better diets are needed to address the macronutritional needs of an ageing population. Short-term clinical trials have demonstrated the health benefits of low-carbohydrate diets (LCDs) and low-fat diets (LFDs) for weight loss and heart protection. Now a study published in the Journal of Internal Medicine looks at the effects of these diets on mortality in middle-aged and older adults.

In the study of 371 159 individuals aged 50 to 71 years, 165 698 deaths occurred over a median follow-up of 23.5 years.

A healthy LFD – characterised by low intake of saturated fat and high intakes of plant protein and high-quality carbohydrates – was related to fewer deaths from all causes, from cardiovascular diseases, and from cancers. In contrast, an overall LCD and an unhealthy LCD were associated with significantly higher total, cardiovascular, and cancer mortality rates. A healthy LCD was associated with slightly lower death rates.

“Our results support the importance of maintaining a healthy LFD with less saturated fat in preventing all-cause and cause-specific mortality among middle-aged and older people,” the authors wrote.

Source: Wiley

Categories : Lab Tests and ImagingTags :

Low Power Mode for MRIs Could Cut Energy Use by Half

On By ModernMedia
Credit: Pixabay CC0

Medical centres could save energy and reduce expenses by turning off MRIs and putting them in the lowest power mode instead of idling them when not in use, according to a new Radiology study.

Health care is responsible for up to 4.4% of global carbon emissions, and imaging contributes an outsized share due to its energy-intensive devices, especially MRI. A 2020 study found that three CTs and four MRIs used the same amount of energy per year as a town of 852 people, for example.

Though turning a machine off is better than idling, a substantial amount of MRI energy consumption occurs in “off” mode, which still draws a constant level of power for cooling. To address this, a new “power save” mode was developed that saves even more energy than the “off” mode by cycling cooling components on and off.

UC San Francisco researchers sought to compare energy consumption in the “idle,” “off” and “power save” modes. The researchers found that turning off MRIs overnight for 12 hours reduced their energy use by 25–33%, and that enabling the additional “power save” mode while the machine was off lowered power use by an additional 22–28%. Switching from idle directly to “power save” decreases energy use by 46–51%.

While just one company currently offers the “power save” mode while machines are off, it’s a design strategy worth replicating, the study noted.

“The results of this study demonstrate the potential energy and cost savings any radiology practice can obtain by using these simple power-down methods,” said assistant professor Sean Woolen, MD, first author on the study. “Our goal was to find ways for radiology departments worldwide to reduce their collective environmental footprint.”

Imaging has become increasingly central to medical decision-making, so it’s imperative to evaluate the design and operations of these machines in order to decarbonise health care, added Woolen.

Health Care Industry Would Save Millions

The study was made possible thanks to an academic-industry partnership comprising UCSF, Siemens Healthineers, Siemens USA, and Siemens Smart Infrastructure. Siemens provided technology and funding to equip MRI machines with power meters and install power monitoring software, and UCSF performed data collection and analysis.

The researchers equipped four outpatient MRI scanners from three different vendors with power meters and examined data over 39 days. They calculated energy output, costs (assuming a mean cost of $0.14 per kilowatt hour), and carbon use.

On an annual basis, switching a scanner from “idle” mode to “off” mode for 12 hours saved 12.3 to 21 megawatt hours (MWh) of electricity, where a megawatt is equal to 1000 kilowatts of electricity used continuously for an hour. This translated to annual savings of $1717 to $2943, and 8.7 to 14.9tonnes of C02-equivalent (MTCO2eq), a metric used to compare emissions of greenhouse gases based on their potential to contribute to global warming.

Switching from off to “power save” mode reduced energy use by an additional 8.8 to 11.4MWh and saved $1226 to $1594 and 6.2 to 8.1 MTC02eq per year.

“Often when we talk about how to decarbonise, solutions seem out of reach, but this initiative is proof that innovators everywhere can have impact,” added Barbara Humpton, CEO of Siemens USA. “The technology to decarbonise is here and ours is hard at work, helping industries like health care uncover ways to be more efficient and take concrete action to meet their carbon-reduction targets.”

The potential impact of adopting this technique as an industry standard would not impact patient care and would be an effective strategy to reduce cost and carbon emissions in health care, added Woolen.

Categories : Diseases, Syndromes and Conditions PaediatricsTags :

Face Masks for Kids Slow Aerosol Spread, Especially from Sneezing

On By ModernMedia
Photo by Kelly Sikkema on Unsplash

In a new study published in Pediatric Investigation, researchers demonstrate that face masks reduce the release of exhaled particles when used by school-aged children, helping to slow the spread of various respiratory viruses. While there was little difference between no protection and masking in exhaled particles from breathing, sneezing saw a significant reduction in the number of particles produced.

Respiratory viruses, including SARS-CoV-2, are transmitted via respiratory droplets and aerosols generated by all activities that involve exhalation, including tidal breathing, speaking, singing, coughing, and sneezing. Droplets, large particles subject to gravitational forces, are rapidly deposited from air and form fomites on surfaces. Aerosols, fine solid or liquid particles which remain suspended in the air, can travel long distances (> 6m) and reach high concentrations in poorly-ventilated areas. The relative contribution of the various modes of infection (direct contact, indirect contact via fomite, large droplet, or aerosol) for various respiratory viruses is difficult to determine, but survival of infectious viruses has been demonstrated in aerosols.

For the study, 23 healthy children were asked to perform activities that ranged in intensity (breathe quietly, speak, sing, cough, and sneeze) while wearing no mask, a cloth mask, or a surgical mask.

The production of exhaled particles that were 5μm or smaller, which is the dominant mode of transmission of many respiratory viruses, increased with coughing and sneezing. Face masks, especially surgical face masks, effectively reduced the release of these and other sized particles.

“Understanding the factors that affect respiratory particle emission can guide public health measures to prevent the spread of respiratory infections, which are a leading cause of death and hospitalisation among young children worldwide,” said corresponding author Peter P. Moschovis, MD, MPH, of Massachusetts General Hospital and Harvard Medical School.

Source: Wiley

Categories : CancerTags :

Beta Blockers Plus Chemotherapy Cut Metastasis in Triple Negative Breast Cancer

On By ModernMedia
Breast cancer cells. Image by National Cancer Institute

A new international study has for the first time, identified that beta-blockers could significantly enhance the therapeutic effect of anthracycline chemotherapy in triple negative breast cancer (TNBC) by reducing metastasis. The results are published in Science Translational Medicine.

Anthracyclines are a class of drugs used in chemotherapy to treat many cancers, including TNBC.

Monash University researchers have previously shown in a clinical trial that beta blockers are linked with reduced metastasis. However, until now, it was unclear how beta-blockers would interact with common cancer treatments.

In this new study, the team used mouse models of cancer and analysed large-scale patient clinical data, in collaboration with the Cancer Registry of Norway, to discover that anthracycline chemotherapy on its own, in the absence of a beta-blocker, induces nerve growth in tumours.

However, adding a beta blocker to chemotherapy inhibited nerve fibre activity in tumours and stopped the cancer from coming back after treatment.

Lead author Dr Aeson Chang said the findings reveal an unanticipated insight into why chemotherapy treatment does not always work as it should.

“We set out to build on previous studies that have shown beta-blockers can halt the stress response experienced by cancer patients at the time of diagnosis and stop the cancer from spreading.

In this new study, not only did we discover the biological effect of beta-blockers when used alongside anthracycline chemotherapy, we also discovered why they are effective,” said Dr Chang.

“In mouse models of TNBC, we found that anthracycline chemotherapy was able to increase sympathetic nerve fibre activity in tumours. Activation of these stress neurons can help tumour cells spread and, fortunately, we found that beta blockers could stop this effect. Our hope is that this exciting discovery will pave the way for further research and, ultimately, lead to improved outcomes for patients.”

Senior author, Professor Erica Sloan, who has been exploring the use of beta-blockers as a novel strategy to slow cancer progression for a number of years, said the study provides important clues about why beta-blockers may help improve the clinical management of TNBC.

“While many patients will be cured by treatment, unfortunately, in some patients the cancer may return – this study has helped us understand why. Our findings show that anthracycline chemotherapy supports the growth of nerves, which can support cancer relapse. This is important, as it tells us that targeting nerves using a beta blocker can improve response to treatment,” said Professor Sloan.

“Beta blocker use has been consistently linked to reduced metastatic relapse and cancer-specific survival in TNBC patients. However, the lack of understanding of how beta blockers improve chemotherapy – which is a core component of the standard treatment for TNBC – has limited the translation of these findings into the cancer clinic,” said Professor Sloan.

“We believe this study presents an exciting opportunity to further explore the use of beta-blockers as a novel strategy in the treatment of TNBC.”

Source: Monash University

Categories : Pain ManagementTags :

Avoiding Addiction and Hallucination in the Quest for New Anaesthetics

On By ModernMedia
Photo by Louis Reed on Unsplash

Strategies to treat pain without triggering dangerous side effects such as euphoria and addiction have proven elusive. For decades, scientists have attempted to develop drugs that selectively activate one type of opioid receptor to treat pain while not activating another type of opioid receptor linked to addiction. Unfortunately, those compounds can cause a different unwanted effect: hallucinations. But a new study published in the journal Nature has identified a potential route to pain relief that neither triggers addiction nor activates the pathway that causes hallucinations.

Painkilling drugs such as morphine and oxycodone, as well as illegal street drugs such as heroin and fentanyl, activate what are known as mu opioid receptors on nerve cells. Those receptors relieve pain but also cause euphoria, contributing to addiction. An alternative strategy is to target another opioid receptor, called the kappa opioid receptor. Scientists attempting to make drugs that target only the kappa receptor have found that they also effectively relieve pain, but they can be associated with other side effects such as hallucinations.

Research led by Washington University School of Medicine in St. Louis has identified the potential mechanisms behind such hallucinations, with the goal of developing painkillers without this side effect. Using electron microscopes, the researchers identified the way that a natural compound related to the salvia plant selectively binds only to the kappa receptor but then causes hallucinations.

“Since 2002, scientists have been trying to learn how this small molecule causes hallucinations through kappa receptors,” said principal investigator Tao Che, PhD, an assistant professor of anesthesiology. “We determined how it binds to the receptor and activates potential hallucinogenic pathways, but we also found that other binding sites on the kappa receptor don’t lead to hallucinations.”

Developing new drugs to target these other kappa receptor binding sites may relieve pain without either the addictive problems associated with older opioids or the hallucinations associated with the existing drugs that selectively target the kappa opioid receptor.

Targeting the kappa receptor to block pain without hallucinations would be an important step forward, according to Che, because opioid drugs that interact with the mu opioid receptor have led to the current opioid epidemic, causing more than 100 000 overdose deaths in the US in 2021.

“Opioids, especially synthetic opioids such as fentanyl, have contributed to far too many overdose deaths,” Che said. “There’s no doubt we need safer pain-relieving drugs.”

Che’s team, led by first author Jianming Han, PhD, a postdoctoral research associate in Che’s laboratory, found that a class of signaling proteins called G proteins cause the kappa opioid receptor to activate several different pathways.

“There are seven G proteins linked to the kappa receptor, and although they are very similar to each other, the differences between the proteins may help explain why some compounds can cause side effects such as hallucinations,” Han said. “By learning how each of the proteins binds to the kappa receptor, we expect to find ways to activate that receptor without causing hallucinations.”

The function of the G proteins has largely been unclear until now, particularly the protein that activates the pathway lined to hallucinations.

“All of these proteins are similar to one another, but the specific protein subtypes that bind to the kappa receptor determine which pathways will be activated,” Che said. “We have found that the hallucinogenic drugs can preferentially activate one specific G protein but not other, related G proteins, suggesting that beneficial effects such as pain relief can be separated from side effects such as hallucinations. So we expect it will be possible to find therapeutics that activate the kappa receptor to kill pain without also activating the specific pathway that causes hallucinations.”

Source: Washington University School of Medicine

Categories : Mental HealthTags :

Depression Treatment Sees Positive Results from Lysergide Microdosing

On By ModernMedia
Photo by Andrew Neel on Unsplash

Researchers have released positive topline data from a trial evaluating microdoses of lysergide, commonly known as LSD, in the treatment of major depressive disorder (MDD). The investigator-initiated Phase 2 trial was led by Prof Matthias Liechti and Dr Felix Mueller at University Hospital Basel (UHB) and the University Hospital of Psychiatry, and supported by Mindmed.

Lysergide is a potent semi-synthetic hallucinogen that has gained some notoriety as an illicit drug but in recent years has been investigated as a treatment for MDD, alongside other psychedelic drugs. The new trial compared lower and higher doses of lysergide, though at still small doses. Previous research also showed benefits in treating anxiety.

The topline data demonstrated significant, rapid, durable and beneficial effects of lysergide and its potential to mitigate symptoms of MDD. The high dose lysergide regimen in which 28 patients received 100µg at their first dosing day and 200µg at their second dosing day (separated by four weeks) resulted in statistically and clinically significant improvements on the primary endpoint, which was the change in clinician-rated depressive scores 6 weeks after the first administration as compared to control (whether or not the patient received a second administration).  The 27 members of the control group received a lower dose regimen of 25µg on both treatment days. Both groups had improvements compared to the placebo group. Data from the secondary endpoints were also encouraging, and the investigational drug was generally well-tolerated, as indicated by reported adverse events, changes in vital signs and laboratory values.

“We continue to be encouraged by the positive results being generated on the clinical activity of lysergide by our collaborators at UHB,” said Robert Barrow, Chief Executive Officer and Director of MindMed, the company behind the trial. “The statistically and clinically significant improvements observed in this study reinforce preliminary findings that have shown the clinical potential of lysergide in anxiety, depression and other brain health disorders.  These positive findings are particularly relevant to our MM-120 program in generalized anxiety disorder, given the high degree of comorbidity of GAD and MDD. I would like to congratulate and thank our collaborators at UHB for once again generating high quality clinical data that continue to support the progression of our pipeline.” 

Prof. Matthias Liechti, co-primary investigator of the trial, commented, “Historical studies of lysergide in MDD demonstrated rapid, robust and sustained improvement in depressive symptoms. We also observed improvement in depressive symptoms in patients with anxiety disorders in another of our recently published trials. We believed it was necessary to confirm the historical studies with ones using modern methods. Hence, we designed this randomised-controlled trial to assess the benefits of lysergide treatment in MDD. Importantly, an active small dose of lysergide was used as the control. We are extremely encouraged by the results we presented today, which demonstrate the strong, rapid and enduring improvements of this compound in patients suffering from MDD. We look forward to publishing the completed results in a peer-reviewed journal along with additional analyses. Our lab will continue investigating the therapeutic potential of lysergide and other psychedelics.”

MindMed supports the UHB Liechti Lab in conducting investigator-initiated trials for lysergide and other novel therapies and has exclusive access and rights to the data generated by these studies.

Source: MindMed

Categories : Cardiovascular DiseaseTags :

Time to Rethink Beta Blockers as Secondary Prevention for Heart Attack Survivors?

On By ModernMedia
Photo by Robina Weermeijer on Unsplash

Secondary prevention after a heart attack, where beta blockers are used over the long term to curb the risk of further heart attacks or death, doesn’t seem to be warranted in patients who don’t have heart failure, suggests a large study published in the journal Heart.

The researchers found no difference in these risks between patients taking beta blockers more than a year after their heart attack and those not on these drugs.

Beta blockers are mostly used to manage abnormal heart rhythms, as well as angina and high blood pressure. They are routinely prescribed after a heart attack as secondary prevention to lower the risk of recurrence and other cardiovascular complications.

But it’s not clear if these drugs are warranted in patients who don’t have heart failure, or a potentially fatal complication of heart attack known as left ventricular systolic dysfunction (LVSD) beyond the first year.

Most of the current evidence is based on the results of clinical trials that predate major changes to the routine care of heart attack patients, explain the researchers.

The researchers drew on 43 618 adults who had had a heart attack between 2005 and 2016 that required hospital treatment, and whose details had been entered into the national Swedish register for coronary heart disease (SWEDEHEART).

None of these patients had heart failure or LVSD: 34 253 of them were prescribed beta blockers and were still on these drugs 1 year after hospital discharge; 9365 hadn’t been prescribed these drugs. Their average age was 64 and around 1 in 4 were women.

The researchers wanted to find out if there were any differences between the two groups in terms of deaths from any cause and rates of further heart attacks, revascularisation, or hospitalisation for heart failure.

The real time data showed that long term treatment with beta blockers wasn’t associated with improved cardiovascular outcomes during an average monitoring period of 4.5 years.

Some 6475 (19%) of those on beta blockers, and 2028 (22%) of those who weren’t, died from any cause, or had another heart attack, or required unscheduled revascularisation, or were admitted to hospital for heart failure.

After accounting for potentially influential factors, including demographics and relevant co-existing conditions, no significant difference was seen in rates of these events between the two groups.

As an observational study, it can’t establish cause. Additionally, despite being the largest study of its kind to date, the findings should be viewed in the context of certain limitations, acknowledge the researchers.

Patients weren’t randomised to treatment; only certain cardiovascular outcomes were included; there was no indication of how consistently patients took their drugs; nor any information on their health related quality of life.

And there were some differences between the two groups in respect of factors known to influence the risk of poor cardiovascular outcomes.

But, the researchers point out, beta blockers are associated with several side effects such as depression and fatigue, and it’s now time to reassess the value of long term treatment with these drugs in heart attack patients who don’t have heart failure or LVSD, they suggest.

In a linked editorial, Professor Ralph Stewart and Dr Tom Evans write: “Despite strong evidence that long-term beta-blockers can improve outcomes after [heart attack], it has been uncertain whether this benefit applies to lower risk patients who are taking other evidence-based therapies and who have a [normal functioning heart].”

They point out: “Recommendations on the duration of beta blocker therapy are variable or absent because this question was not specifically evaluated in clinical trials. Most patients take daily medications for many years after a [heart attack] because they believe they are beneficial.”

And they conclude: “[This] study raises an important question directly relevant to the quality of care –do patients with a normal [functioning heart] benefit from long term beta-blocker therapy after [heart attack]? To answer this question, more evidence from large randomised clinical trials is needed.”

Source: EurekAlert!

Categories : Genetics HIVTags :

Curing HIV with a Dual Gene Editing Approach

On By ModernMedia
Source: Pixabay CC0

Gene editing therapy aimed at two targets – HIV-1 and CCR5, the co-receptor that helps the virus get into cells – can effectively eliminate HIV infection, report scientists in PNAS. This is the first to combine a dual gene-editing strategy with antiretroviral drugs to cure animals of HIV-1.

“The idea to bring together the excision of HIV-1 DNA with inactivation of CCR5 using gene-editing technology builds on observations from reported cures in human HIV patients,” said Kamel Khalili, PhD, professor at the Lewis Katz School of Medicine. “In the few instances of HIV cures in humans, the patients underwent bone marrow transplantation for leukaemia, and the donor cells that were used carried inactivating CCR5 mutations.”

Dr Khalili and Howard E. Gendelman, MD, professor at UNMC, were senior investigators on the new study from the Lewis Katz School of Medicine at Temple University and the University of Nebraska Medical Center (UNMC). The two researchers have been long-time collaborators and have strategically combined their research strengths to find a cure for HIV.

“We are true partners, and what we achieved here is really spectacular,” Dr Gendelman said. “Dr Khalili’s team generated the essential gene-editing constructs, and we then applied those constructs in our LASER-ART mouse model at Nebraska, figuring out when to administer gene-editing therapy and carrying out analyses to maximise HIV-1 excision, CCR5 inactivation, and suppression of viral growth.”

In previous work, Drs Khalili and Gendelman and their respective teams showed that HIV can be edited out from the genomes of live, humanised HIV-infected mice, leading to a cure in some animals. For that research, CRISPR gene-editing technology for targeting HIV-1 was combined with a therapeutic strategy known as long-acting slow-effective release (LASER) antiretroviral therapy (ART). LASER ART holds HIV replication at low levels for long periods of time, decreasing the frequency of ART administration.

Despite being able to eliminate HIV in LASER-ART mice, the researchers found that HIV could eventually re-emerge from tissue reservoirs and cause rebound infection. This effect is similar to rebound infection in human patients who have been taking ART but suddenly stop or experience a disruption in treatment. HIV integrates its DNA into the genome of host cells, it can lie dormant in tissue reservoirs for long periods of time, out of reach of antiretroviral drugs. As a consequence, when ART is stopped, HIV replication renews, giving rise to AIDS.

To prevent rebound infection, Dr Khalili and colleagues began work on next-generation CRISPR technology for HIV excision, developing a new, dual system aimed at permanently eliminating HIV from the animal model. “From success stories of human HIV patients who have undergone bone marrow transplantation for leukaemia and been cured of HIV, our hypothesis was that the loss of the virus’s receptor, CCR5, is important to permanently eliminating HIV infection,” he explained. They developed a simple and more practical procedure for the inactivation of CCR5 that includes an IV inoculation of the CRISPR gene editing molecule.

Experiments in humanized LASER-ART mice carried out by Dr Gendelman’s team showed that the constructs developed at Temple, when administered together, resulted in viral suppression, restoration of human T-cells, and elimination of replicating HIV-1 in 58% of infected animals. The findings support the idea that CCR5 has a key role in facilitating HIV infection.

The Temple team also anticipates soon testing the dual gene-editing strategy in non-human primates.

The new dual CRISPR gene-editing strategy holds exceptional promise for treating HIV in humans. “It is a simple and relatively inexpensive approach,” Dr Khalili noted. “The type of bone marrow transplant that has brought about cures in humans is reserved for patients who also have leukaemia. It requires multiple rounds of radiation and is not applicable in resource-limited regions, where HIV infection tends to be most common.”

Source: Temple University Health System

Categories : Diseases, Syndromes and Conditions New Compounds and TreatmentsTags :

Searching for Broad-spectrum Antiviral Agents for the Next Pandemic

On By ModernMedia
Photo by National Cancer Institute on Unsplash

A new study has identified potential broad-spectrum antiviral agents that can target multiple families of RNA viruses with pandemic potential. The study, published in Cell Reports Medicine, tested an array 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 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 for the next pandemic after COVID. These include 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.”

Led by Gustavo Garcia Jr. in the UCLA Department of Molecular and Medical Pharmacology, 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 defence against cancer,” said senior author Vaithi Arumugaswami, Associate Professor in the UCLA Department of Molecular and Medical Pharmacology.

“A robust host antiviral response induced by a single dose treatment of STING agonist cAIMP is effective in preventing and mitigating the debilitating viral arthritis caused by Chikungunya virus in a mouse model. This is a very promising treatment modality as Chikungunya virus-affected individuals suffer from viral arthritis years and decades from the initial infection,” Arumugaswami added.

“At molecular level, CHIKV contributes to robust transcriptional (and chemical) imbalances in infected skin cells (fibroblasts) compared to West Nile Virus and ZIKA Virus, reflecting a possible difference in the viral-mediated injury (disease pathogenesis) mechanisms by viruses belonging to different families despite all being mosquito-borne viruses,” said senior author Arunachalam Ramaiah, Senior Scientist in the City of Milwaukee Health Department.

“The study of transcriptional changes in host cells reveals that cAIMP treatment rescues (reverses) cells from the harmful effect of CHIKV-induced dysregulation of cell repair, immune, and metabolic pathways,” Ramaiah added.

The study concludes that the STING agonists exhibited broad-spectrum antiviral activity against both arthropod-borne- and respiratory viruses, including treaded SARS-CoV-2 and Enterovirus D68 in cell culture models.

Garcia notes, “The next step is to develop these broad-spectrum antivirals in combination with other existing antivirals and be made readily available in the event of future respiratory and arboviral disease outbreaks.”

Source: University of California – Los Angeles Health Sciences