
via Global Biodefense
Animal study shows treatment blocks inflammation and protects lungs without killing the flu virus
The raging lung inflammation that can contribute to death from the flu can be stopped in its tracks by a drug derived from a naturally occurring human protein, a new animal study suggests.
In mouse studies, all untreated animals given a lethal dose of influenza died within days. All but one of the infected mice treated with the experimental therapy not only survived, but remained energetic and kept weight on – despite having high levels of the flu virus in their lungs.
The experimental treatment is a heavy dose of MG53, part of a family of proteins that plays an essential role in cell membrane repair. Already identified as a potential therapy for conditions ranging from Alzheimer’s disease to persistent skin wounds, MG53 was found in this study to prevent death from a lethal flu infection by blocking excessive inflammation – without having any effect on the virus itself.
The researchers are currently testing the effects of the therapy in mice infected with SARS-CoV-2, the coronavirus that causes COVID-19.
“I haven’t ever seen anything like this before,” said Jacob Yount, associate professor of microbial infection and immunity at The Ohio State University and co-lead author of the study. “Even though these mice had the same viral load as the untreated mice, they didn’t get very sick – with the lethal dose of the flu.”
Yount, whose lab studies the immune response against viral infections, co-led the work with Jianjie Ma, professor of cardiac surgery at Ohio State, who discovered MG53 and its role in cell repair and has been developing the protein as a therapeutic agent.
The paper was published online Oct. 8 in the American Journal of Respiratory and Critical Care Medicine, and will appear in a future print issue.
The collaboration between the two labs in Ohio State’s College of Medicine on this work grew out of a proposal by Matthew Sermersheim, a graduate student in Ma’s lab, to expand on the investigation of MG53’s links to inflammation. In the July 17 issue of Nature Communications, Sermersheim was the first author of a study showing that the lungs of mice lacking the MG53 gene and infected with flu responded with extensive inflammation compared to normal mice – indicating that MG53 has a protective role in the immune response.
For this new work, the scientists put MG53 to the test against influenza, which, along with other respiratory viruses, is a top-10 cause of death worldwide.
The researchers infected mice with a dose of an H1N1 strain of influenza and treated half with a placebo. Using recombinant human MG53, a molecule Ma’s lab has been developing as a drug, the researchers treated the other half of mice with seven daily injections beginning 24 hours after infection. The untreated mice showed an aggressive loss of weight and died within nine days, but 92% of the treated mice lost very little weight, remained active and returned to their normal weight by two weeks after infection.
“The protein has a way to recognize tissue that’s been injured and it can go there directly,” Ma said. “We are basically enhancing a natural anti-inflammatory mechanism in the body so that when you face the crisis of an aggressive virus infection, the body can better defend itself.”
Despite the strikingly different outcomes, the viral loads in both sets of mice were similar – meaning an MG53-based agent is not an anti-viral drug. Even teeming with the flu virus, the airways of treated mice showed little tissue damage.
Though the team is still working to fully identify how this protection occurs, the researchers determined that MG53 stops an immune response mishap called a “cytokine storm,” which leads to tissue damage. The research also showed that MG53 mitigates an infection-related cell-death process called pyroptosis, which also promotes inflammation and lung dysfunction.
“A lot of the lung damage with the flu virus is actually caused by excessive inflammation from our own immune response,” Yount said. “If you can dampen that hyperactive immune response, you’ll have less tissue damage, even though the virus is still replicating at really high levels.”
Lung tissue damaged by inflammation is deadly because it allows fluid and cells to build up in airways, preventing the lungs from absorbing oxygen.
Ma’s previous work in animal models suggests driving up levels of MG53 in the body for therapeutic purposes is safe: Mice his lab has genetically engineered to over-produce the protein live longer and healthier lives than normal mice. Though the scientists envision MG53 as part of a cocktail of drugs targeting deadly viral infections, they caution that much more research is needed before a therapy is available for humans.
“We need better anti-inflammatory tissue repair therapies,” Ma said. “We don’t have COVID-19 data yet, but even with influenza, which hits us on a seasonal basis, this application could make quite a bit of difference.”
The Latest Updates from Bing News & Google News
Go deeper with Bing News on:
Influenza lung damage
- Here's How Quickly You Can Get Infected With The Flu After An Exposure
After being infected with the flu, it takes between 1 and 5 days for symptoms to occur, experts told HuffPost. Symptoms could be fever, chills, headache, cough, runny nose and more, said Dr. Marcel ...
- Annual Flu Vaccine: Crucial in Preventing Severe Flu Complications
Your immune system has to be strong to fight the bacteria and viruses that enter the body and cause illness particularly during the cold and flu season. Learn how to boost your immunity by following ...
- Roll up your sleeve for National Influenza Vaccination Week
Estes Park Health wants to remind everyone that December 3-9 is National Influenza Vaccination Week. The American Lung Association reminds us that as we head into flu season, remember to keep ...
- What Is White Lung Syndrome and How Is It Treated? Doctors Explain
While “white lung” is being used lately to refer to pneumonia, other things can lead to this effect, says Gustavo Cumbo-Nacheli, M.D., a pulmonologist with Corewell Health. “Many conditions could ...
- Complications from flu largely preventable with annual flu vaccine
During National Influenza Vaccination Week (December 4-8, 2023), leading public health organizations are encouraging everyone to get a flu shot if they have not already done so. The flu is more than ...
Go deeper with Google Headlines on:
Influenza lung damage
[google_news title=”” keyword=”influenza lung damage” num_posts=”5″ blurb_length=”0″ show_thumb=”left”]
Go deeper with Bing News on:
MG53
- Is MG53 a potential therapeutic target for cancer?
MG53, a member of the TRIM protein family, shows strong potential in cancer therapy, primarily due to its E3 ubiquitin ligase properties. The classic membrane repair function and anti-inflammatory ...
- Koyal Garg, Ph.D.
Corona BT, Garg K, Roe JL, Zhu H, Park KH, Ma J, Walters TJ (2014), The Effect of Recombinant Human MG53 Protein on Tourniquet-Induced Ischemia Reperfusion Injury in Rat Muscle, Muscle & Nerve, 49 (6) ...
- Modulation of Wound Healing and Scar Formation (IMAGE)
This image shows modulation of wound healing and scar formation by MG53-mediated cell membrane repair and TGF-β signaling regulation. This image may be used only with appropriate caption and ...
- MG53 Protein Protects Aortic Valve Interstitial Cells From Membrane Injury and Fibrocalcific Remodeling
Given the tremendous stress experienced by heart valves and the crucial contributions of fibrocalcific signaling to valve disease, we hypothesized that MG53 can both facilitate repair of acute ...
- ASSA14-03-10 Effects of MG53 preconditioning on ischemia/reperfusion-induced arrhythmias in the isolated rat hearts
Background MG53 preconditioning has been proven to protect the hearts against ischemia/reperfusion (I/R) injury, manifested mainly by reduced myocardial specific biomarker, and decreased infarct size.
Go deeper with Google Headlines on:
MG53
[google_news title=”” keyword=”MG53″ num_posts=”5″ blurb_length=”0″ show_thumb=”left”]