IrsiCaixa AIDS Research Institute

COVID-19, as everyone knows by now, is much more than a respiratory illness. And many of its longer-term effects and seemingly secondary issues are often puzzling, such as an increase in new-onset diabetes among people with COVID-19 infections. New research has gained a better understanding of why. For that and more research news, continue reading. COVID-19 and New-Onset Diabetes An increase in new-onset diabetes has been associated with COVID-19 infections, although why is largely unknown. Researchers at Osaka University in Japan appear to have found a link. The key seems to be interfering with insulin signaling. COVID-19 can cause problems with metabolism, even though it is generally viewed as a respiratory illness. Although by now, it’s clear that the virus and resultant disease has far-reaching effects. They published their research in the journal Metabolism. “The insulin/IGF signaling pathway is a key pathway in the regulation of energy metabolism and cell survival,” Jihoon Shin, Ph.D., first author of the study, said. “Therefore, we suspected that SARS-CoV-2 affects this signaling pathway to cause problems with blood sugar regulation.” They analyzed gene expression in patients in addition to in vivo and in vitro models of SARS-CoV-2 infection. They were scanning for noticeably over- or under-expressed genes compared to uninfected patients, animals or cells. The SARS-CoV-2 infection affected the expression of insulin/IGF signaling pathway components in the lung, liver, adipose tissue, and pancreatic cells. The changes were attributed partially to activation of interferon regulatory factor 1 (IRF1). IRF1 expression is elevated in older patients, men, obese people, and patients with diabetes. The synergistic effects of age, male sex, obesity and diabetes with the virus demonstrated IRF1 expression increased, suggesting why these cohorts are more vulnerable to the disease. Also, critical COVID-19 patients had higher IRF 1 expression and lower insulin/IGF signaling pathway genes in the blood compared to noncritical patients. They found that treating infected cells or an animal model with hormonal factors that decreased IRF1 expression improved insulin/IGF signaling. “Our findings suggest that SARS-CoV-2 infection impairs insulin/IGF signaling by increasing IRF1 expression, thereby disrupting blood sugar metabolism,” Shin said. “Decreasing IRF1 expression by treatment with factors such as dihydrotestosterone and dexamethasone could help mitigate the effects of COVID-19.” Older Drug Appears to Improve Checkpoint Inhibitors Researchers with Degron Therapeutics published a study suggesting an older drug, Bristol Myers Squibb’s Revlimid (lenalidomide), a molecular glue degrader of IKZF1 and IKZF3, can improve anti-PD-1 checkpoint inhibitors to treat cancer. The study found that lenalidomide bypasses CD28 co-stimulation to reinstate PD-1 immunotherapy by activating Notch signaling. In short, lenalidomide appears to help checkpoint inhibitors work better. The drug was approved in 2005 to treat myeloma and has since been indicated for multiple myeloma, deletion 5q myelodysplastic syndrome (MDS), mantle cell lymphoma, and other hematological tumors. PD-1 is a checkpoint protein on T cells that typically acts as an off switch that prevents T cells from attacking other cells in the body. By inhibiting PD-1, it allows T cells to better attack the cancer cells. The research was published in Cell Chemical Biology. Flu Vaccine Associated with 40% Lower Risk of Alzheimer’s Disease A study by the University of Texas Health Science Center at Houston found that people who received at least one flu vaccine were 40% less likely to develop Alzheimer’s disease over the course of four years. They evaluated a large nationwide sample of U.S. adults aged 65 and older. This study came two years after the same researchers identified a possible association between the flu vaccine and decreased risk of Alzheimer’s, only in a much larger sample size, which included 935,887 people who received flu vaccines and 935,887 people who did not. About 5.1% of those vaccinated during the four-year follow-up appointments developed Alzheimer’s, while 8.5% in the non-vaccinated group developed Alzheimer’s. The mechanism isn’t understood, and other vaccines appear to offer some protection against Alzheimer’s, so they suspect it might have to do with how the immune system is activated via vaccines. How T-Cells Are Trained to ID Pathogens Investigators with Harvard Medical School identified a new mechanism that trains immature immune cells to ignore the body’s tissues while attacking pathogens. In this process, specialized thymus cells “pose” as different tissues, preparing the immune system to tell the difference between “friend and foe.” Then, immune cells that react mistakenly to the body’s proteins are eliminated or given other jobs. T-cells originate and are trained in the thymus. The thymus recreates your body, presenting different types of tissue proteins to the immature T-cells to teach them to ignore these cells. They note that it glitches in this recognition system that can lead to autoimmune diseases. The cells in the thymus that can mimic different tissues are called mimetic cells, and they work by co-opting various transcription factors, essentially taking on the identities of tissues such as skin, lung, liver or intestine. If these nascent T-cells mistakenly react against the self-proteins, they either are given a command to self-destruct or are repurposed into other types of T-cells that put a brake on other immune cells. Common HIV Drug Improves Cognition in Mouse Model of Down Syndrome Scientists with the Center for Genomic Regulation and the IrsiCaixa AIDS Research Institute tested lamivudine, a common antiretroviral drug for HIV, in a mouse model of Down syndrome. They found that it improved cognition in the mice. Confirmatory studies in humans would have to be conducted to see if it had the same effect. Retrotransposons are segments of DNA that change location within the genome by making RNA copies of themselves that switch back into DNA at another location. They can insert themselves into specific areas of the genome and sometimes position themselves in gene-promoting regions associated with neurodegenerative disease, stimulating their activity. Retrotransposition rates increase with age and cellular senescence. HIV and retrotransposons require the same molecule to make copies of themselves, reverse transcriptase. Lamivudine is a reverse transcriptase inhibitor against HIV and has been shown to decrease the activation of retrotransposons in aged mice. A Universal Flu Vaccine? The National Institutes of Health Clinical Center in Bethesda, Maryland, has launched a Phase I trial of a novel, universal flu vaccine. The vaccine candidate, BPL-1357, developed by researchers at the National Institute of Allergy and Infectious Diseases, is a whole-virus vaccine engineered with four non-infectious, chemically inactivated strains low-pathogenicity avian flu virus. In animal studies, all mice received two shots of the vaccine given either intramuscularly or intranasally survived later exposure to lethal doses of each of six different flu virus strains, including subtypes not included in the vaccine. They also conducted similar challenge tests in ferrets with similar results. The volunteers in the study will be randomized 1:1:1 to receive two doses of placebo or vaccine 28 days apart: Group A will receive it intramuscularly with intranasal saline placebo; Group B will receive the vaccine intranasally with intramuscular placebo; Group C will receive placebo both intramuscularly and intranasally. The study will be blinded. “With the BPL-1357 vaccine, especially when given intranasally, we are attempting to induce a comprehensive immune response that closely mimics immunity gained following a natural influenza infection,” Dr. Matthew J. Memoli, M.D., the NAIAD investigator leading the study, said. “This is very different than nearly all other vaccines for influenza or other respiratory viruses, which focus on inducing immunity to a single viral antigen and often do not induce mucosal immunity.”

Lamivudine, a commonly-used antiretroviral drug for treating HIV, improves cognition in a mouse model of Down syndrome, according to the findings of a new study. Though clinical studies are necessary to confirm that the drug elicits a similar effect in humans, the findings pave the way for pharmacological treatments that rescue the relatively rapid cognitive decline in people with Down syndrome that is more commonly seen in much older adults in the general population. Lamivudine, a commonly-used antiretroviral drug for treating HIV, improves cognition in a mouse model of Down syndrome, according to the findings of a joint new study by researchers at the Centre for Genomic Regulation (CRG) and the IrsiCaixa AIDS Research Institute, a centre jointly promoted by the "la Caixa" Foundation and the Department of Health of the Generalitat de Catalunya. The research is published today in the Journal of Cellular and Molecular Medicine. Though clinical studies are necessary to confirm that the drug elicits a similar effect in humans, the initial research highlights the potential of using pharmacological interventions such as lamivudine -- or other drugs capable of blocking the same therapeutic target -- as a treatment for ameliorating cognitive impairment of people with Down syndrome. Down syndrome is a condition in which a person has an extra chromosome. Typically, a baby is born with 46 chromosomes. Babies with Down syndrome have an extra copy of one of these, the 21st chromosome. This results in mild to moderate intellectual disability, affecting general cognition traits such as memory, attention span and speaking ability. Adults with Down syndrome also experience accelerated aging, resulting in relatively rapid cognitive decline more commonly seen in much older adults in the general population. People with Down syndrome are also at increased risk of Alzheimer's disease. Chromosome 21 plays an important role in this relationship as it carries a gene -- amyloid precursor protein (APP) -- that produces amyloid proteins that build up in the brain and are associated with disrupting brain function. Amyloid accumulation is common in most adults over the age of 40 with Down syndrome. To aid independent living, most people with Down syndrome undergo psychosocial interventions such as cognitive stimulation therapy, one of the only treatment options currently available. However, no pharmacological interventions exist to date. Targeting retrotransposons is a new unexplored option for Down syndrome that this work demonstrates is of great therapeutic interest. Retrotransposons are segments of DNA that change their location within the genome by making RNA copies of themselves that jump back into DNA at another location. Retrotransposons can insert themselves into specific areas of the genome and, by chance, position themselves in gene-promoting regions associated with neurodegenerative diseases, enhancing their activity. Rates of retrotransposition increase with age and cellular senescence. Retrotransposons show some similarities to HIV, rapidly replicating within cells, though not necessarily with pathological implications. The authors of the study hypothesized that using existing inhibitors that currently target the replication of HIV -- such as the enzyme reverse transcriptase -- could also work to block retrotransposons. "Both HIV and retrotransposons need the same molecule to make copies of themselves: the reverse transcriptase enzyme," explains Dr. Bonaventura Clotet, Director of IrsiCaixa. "We know that lamivudine, a reverse transcriptase inhibitor used against HIV, was shown in aged mice to decrease the activation of retrotransposons which could be linked to age-associated disorders. Therefore, we thought that it could be useful to counteract the cognitive impairment associated with Down syndrome," he adds. The researchers used Ts65Dn mice, the most widely-studied Down syndrome animal model to date. For a period of four months, mice were treated with lamivudine, with another control group receiving water. The researchers then carried out various behavioural experiments designed to test locomotor activity, recognition memory and anxiety. They found that mice receiving lamivudine showed improved cognition. The authors of the study hypothesise that the observed benefits of lamivudine could be due to its effect on one or more variants of the APP gene. "Our work aims to support people with Down syndrome and their families by providing them more options to live independent lives, particularly those affected by early-stage Alzheimer's disease," says Dr. Mara Dierssen, researcher at the CRG and co-author of the study. "We still need pharmacological treatments that consistently help improve memory, attention and language functions, or prevent cognitive decline associated with ageing. This study is one step aiming to change that, revealing retrotransposition as an interesting mechanism to pursue not only in ageing but also in neurodevelopmental disorders," concludes Dr. Dierssen. Lamivudine is a prescription medicine approved by both the United States and European Union medical authorities for the treatment of HIV infection in adults and children. The researchers' next plan to initiate clinical trials with the drug for people with Down syndrome and Alzheimer's disease.

STOCKHOLM, March 31, 2021 /PRNewswire/ -- The IrsiCaixa AIDS Research Institute has carried out tests and today presented a report which shows that LightAir's technology IonFlow neutralizes viruses that mimic SARS-CoV-1 and SARS-CoV-2 in drop form on surfaces. This evidence can now be added to a seven-year scientific study from Karolinska Institute that previously showed the technology's effectiveness against airborne viruses and how it greatly reduces the spread of infection. "We measured out various versions of pseudoviruses* that mimic the entry of different coronaviruses into cells. The conclusion is that in the form of droplets on exposed surfaces, IonFlow technology has a clear inhibition on viral entry already within 30 minutes," says Nuria Izquierdo Useros, Supervisor/PhD and the principal investigator of the study at IrsiCaixa. "Personally, I find this extremely interesting, and the potential of this technology to combat virus spreading should be further investigated. Not least in these times, and especially given that this technology attacks the viral entry process so viruses can no longer infect human cells." IrsiCaixa is a leading center for research into infectious diseases, located in Barcelona, Spain. The purpose of their tests was to show if LightAir IonFlow high-density ionization neutralizes two corona pseudoviruses: SARS-CoV-2, which causes the disease COVID19, and SARS-CoV-1, which causes the disease SARS. "It is both stimulating and gratifying that we have now been able to supplement the previous in-depth study from Karolinska Institute, which so clearly shows how our technology prevents the spread of a number of viruses," says Lars Liljeholm, CEO of LightAir. "From my perspective, there is little reason to suspect that there might be any virus that can't be inhibited by our technology. We are proud to be able to contribute to the reduction of viral infections in homes, offices, schools and other shared spaces." * The intention of the test was to assess the capacity of inhibiting viral entry of both SARS-1 and SARS-2 pseudoviruses, which is a proof of principle of the efficacy of this strategy against different coronaviruses. Pseudoviruses are manipulated in the laboratory to mimic viral entrance into cells just once and are considered ideal to test the efficacy of antivirals, antibodies or strategies aimed at inhibiting viral entry. CONTACT: For further information, please contact: Lars Liljeholm CEO LightAir AB (publ) +46 (0)70 828 61 96 lars.liljeholm@lightair.com This information was brought to you by Cision The following files are available for download: View original content: SOURCE LightAir Company Codes: ISIN:SE0008963888