5-minute breathing workout lowers blood pressure as much as exercise, drugs

 Working out just five minutes daily via a practice described as "strength training for your breathing muscles" lowers blood pressure and improves some measures of vascular health as well as, or even more than, aerobic exercise or medication, new CU Boulder research shows.

The study, published June 29 in the Journal of the American Heart Association, provides the strongest evidence yet that the ultra-time-efficient maneuver known as High-Resistance Inspiratory Muscle Strength Training (IMST) could play a key role in helping aging adults fend off cardiovascular disease -- the nation's leading killer.

In the United States alone, 65% of adults over age 50 have above-normal blood pressure -- putting them at greater risk of heart attack or stroke. Yet fewer than 40% meet recommended aerobic exercise guidelines.

"There are a lot of lifestyle strategies that we know can help people maintain cardiovascular health as they age. But the reality is, they take a lot of time and effort and can be expensive and hard for some people to access," said lead author Daniel Craighead, an assistant research professor in the Department of Integrative Physiology. "IMST can be done in five minutes in your own home while you watch TV."

Developed in the 1980s as a way to help critically ill respiratory disease patients strengthen their diaphragm and other inspiratory (breathing) muscles, IMST involves inhaling vigorously through a hand-held device which provides resistance. Imagine sucking hard through a tube that sucks back.

Initially, when prescribing it for breathing disorders, doctors recommended a 30-minute-per-day regimen at low resistance. But in recent years, Craighead and colleagues have been testing whether a more time-efficient protocol -- 30 inhalations per day at high resistance, six days per week -- could also reap cardiovascular, cognitive and sports performance improvements.

For the new study, they recruited 36 otherwise healthy adults ages 50 to 79 with above normal systolic blood pressure (120 millimeters of mercury or higher). Half did High-Resistance IMST for six weeks and half did a placebo protocol in which the resistance was much lower.

After six weeks, the IMST group saw their systolic blood pressure (the top number) dip nine points on average, a reduction which generally exceeds that achieved by walking 30 minutes a day five days a week. That decline is also equal to the effects of some blood pressure-lowering drug regimens.

Even six weeks after they quit doing IMST, the IMST group maintained most of that improvement.

"We found that not only is it more time-efficient than traditional exercise programs, the benefits may be longer lasting," Craighead said.

The treatment group also saw a 45% improvement in vascular endothelial function, or the ability for arteries to expand upon stimulation, and a significant increase in levels of nitric oxide, a molecule key for dilating arteries and preventing plaque buildup. Nitric oxide levels naturally decline with age.

Markers of inflammation and oxidative stress, which can also boost heart attack risk, were significantly lower after people did IMST.

And, remarkably, those in the IMST group completed 95% of the sessions.

"We have identified a novel form of therapy that lowers blood pressure without giving people pharmacological compounds and with much higher adherence than aerobic exercise," said senior author Doug Seals, a Distinguished Professor of Integrative Physiology. "That's noteworthy."

The practice may be particularly helpful for postmenopausal women.

In previous research, Seals' lab showed that postmenopausal women who are not taking supplemental estrogen don't reap as much benefit from aerobic exercise programs as men do when it comes to vascular endothelial function. IMST, the new study showed, improved it just as much in these women as in men.

"If aerobic exercise won't improve this key measure of cardiovascular health for postmenopausal women, they need another lifestyle intervention that will," said Craighead. "This could be it."

Preliminary results suggest MST also improved some measures of brain function and physical fitness. And previous studies from other researchers have shown it can be useful for improving sports performance.

"If you're running a marathon, your respiratory muscles get tired and begin to steal blood from your skeletal muscles," said Craighead, who uses IMST in his own marathon training. "The idea is that if you build up endurance of those respiratory muscles, that won't happen and your legs won't get as fatigued."

Seals said they're uncertain exactly how a maneuver to strengthen breathing muscles ends up lowering blood pressure, but they suspect it prompts the cells lining blood vessels to produce more nitric oxide, enabling them to relax.

The National Institutes of Health recently awarded Seals $4 million to launch a larger follow-up study of about 100 people, comparing a 12-week IMST protocol head-to-head with an aerobic exercise program.

Meanwhile, the research group is developing a smartphone app to enable people to do the protocol at home using already commercially available devices.

Those considering IMST should consult with their doctor first. But thus far, IMST has proven remarkably safe, they said.

"It's easy to do, it doesn't take long, and we think it has a lot of potential to help a lot of people," said Craighead.

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Story Source:

Materials provided by University of Colorado at Boulder. Original written by Lisa Marshall. Note: Content may be edited for style and length.

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Journal Reference:

1. Daniel H. Craighead, Thomas C. Heinbockel, Kaitlin A. Freeberg, Matthew J. Rossman, Rachel A. Jackman, Lindsey R. Jankowski, Makinzie N. Hamilton, Brian P. Ziemba, Julie A. Reisz, Angelo D’Alessandro, L. Madden Brewster, Christopher A. DeSouza, Zhiying You, Michel Chonchol, E. Fiona Bailey, Douglas R. Seals. Time‐Efficient Inspiratory Muscle Strength Training Lowers Blood Pressure and Improves Endothelial Function, NO Bioavailability, and Oxidative Stress in Midlife/Older Adults With Above‐Normal Blood Pressure. Journal of the American Heart Association, 2021; DOI: 10.1161/JAHA.121.020980

https://www.sciencedaily.com/releases/2021/06/210630135033.htm

Machine learning helps in predicting when immunotherapy will be effective

 When it comes to defense, the body relies on attack thanks to the lymphatic and immune systems. The immune system is like the body's own personal police force as it hunts down and eliminates pathogenic villains.

"The body's immune system is very good at identifying cells that are acting strangely. These include cells that could develop into tumors or cancer in the future," says Federica Eduati from the department of Biomedical Engineering at TU/e. "Once detected, the immune system strikes and kills the cells."

Stopping the attack

But it's not always so straightforward as tumor cells can develop ways to hide themselves from the immune system.

"Unfortunately, tumor cells can block the natural immune response. Proteins on the surface of a tumor cell can turn off the immune cells and effectively put them in sleep mode," says Oscar Lapuente-Santana, PhD researcher in the Computational Biology group.

Fortunately, there is a way to wake up the immune cells and restore their antitumor immunity, and it's based on immunotherapy.

Introducing immunotherapy

Immunotherapy is a cancer treatment that assists the immune system in its fight against cancer cells. One type of immunotherapy involves immune checkpoint blockers (ICB), which are drugs that tell the immune cells to ignore the shutdown orders coming from cancer cells.

The discovery of ICB has been revolutionary for cancer treatment, with James P. Allison and Tasuku Honjo jointly awarded the 2018 Nobel Prize in Physiology or Medicine for their work on ICB.

Although ICB has been successfully used to treat plenty of patients and different cancer types, only one-third of patients respond to the treatment.

"ICB has had a big impact, but it could be bigger if we could figure out quickly which patients are most likely to respond to the treatment," says Eduati. "And it would also be great if we could understand why other patients are not responding to ICB."

To solve this problem, Lapuente-Santana and Eduati, along with colleagues Maisa van Genderen (TU/e), Peter Hilbers (TU/e) and Francesca Finotello (Medical University of Innsbruck), turned to machine learning to predict how patients might respond to ICB. Their work has just been published in the journal Patterns.

Searching the tumor microenvironment

To predict whether a patient will respond to ICB, the researchers first needed to find particular biomarkers in tumor samples from the patients.

"Tumors contain more than just tumour cells, they also contain several different types of immune cells and fibroblasts, which can have a pro- or anti-tumour role, and they communicatie with each other," explains Lapuente-Santana. "We needed to find out how complex regulatory mechanisms in the tumor microenvironment affect response to ICB. We turned to RNA-sequencing datasets to provide a high-level representation of several aspects of the tumor microenvironment."

To find the right mechanisms that could serve as biomarkers to predict patients' response to ICB, the team searched the microenvironment of tumors using computational algorithms and datasets from previous clinical patient care.

"RNA-sequencing datasets are publicly available, but the information about which patients responded to ICB therapy is only available for a small subset of patients and cancer types," says Eduati. "So, we used a trick to solve the data problem."

The trick

For their trick, instead of looking for the actual biological response to ICB treatment, the researchers picked out several substitute immune responses from the same datasets. Despite not being the primary response to ICB, together they could be used as an indicator of the effectiveness of ICB.

Thanks to this approach, the team could use a large public dataset with thousands of patient samples to robustly train machine learning models.

"A significant challenge with this work was the proper training of the machine learning models. By looking at substitute immune responses during the training process, we were able to solve this," says Lapuente-Santana.

With the machine learning models in place, the researchers then tested the accuracy of the model on different datasets where the actual response to ICB treatment was known. "We found that overall, our machine learning model outperforms biomarkers currently used in clinical settings to assess ICB treatments," says Eduati.

But why are Eduati, Lapuente-Santana, and their colleagues turning to mathematical models to solve a medical treatment problem? Will this replace the doctor? "Mathematical models can provide a big picture of how individual molecules and cells are interconnected, while at the same time approximate the behavior of tumors in a particular patient. In clinical settings, this means that immunotherapy treatment with ICB can be personalized to a patient. It's important to remember that the models can help doctors with their decisions on the best treatment, they won't replace them." says Eduati.

In addition, the model also helps in understanding which biological mechanisms are important for the biological response. Understanding and identifying the mechanisms that mediate ICB response can guide how best to combine ICB with other treatments to improve its clinical efficacy. However, this will first require experimental validation of the identified mechanisms before translating these results to clinical settings.

Dare to DREAM

The machine learning approach presented in the paper was also used by some of the researchers to take part in a DREAM challenge called "Anti-PD1 Response Prediction DREAM Challenge."

DREAM is an organization dedicated to running crowd-sourced challenges involving algorithms in biomedicine. "We came first in one of the sub-challenges and competed under the name cSysImmunoOnco team," adds Eduati.

Our immune system might be an efficient detective and disease hunter, but every now and then it needs a helping hand to eradicate elusive villains like cancer cells. Immunotherapy using immune checkpoint blockers is one such approach, but it doesn't work for everyone.

Lapuente-Santana, Eduati, and colleagues have certainly dared to dream, and their work could prove pivotal in quickly identifying those who could be successfully treated with ICB in the future.

Thanks to machine learning, the researchers hope to rapidly deliver proper and effective cancer treatments to specific patients.

And for some cancer cells, it means that there could be no place to run, and no place to hide.

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Story Source:

Materials provided by Eindhoven University of Technology. Note: Content may be edited for style and length.

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Journal Reference:

1. Óscar Lapuente-Santana, Maisa van Genderen, Peter A.J. Hilbers, Francesca Finotello, Federica Eduati. Interpretable systems biomarkers predict response to immune-checkpoint inhibitors. Patterns, 2021; 100293 DOI: 10.1016/j.patter.2021.100293

https://www.sciencedaily.com/releases/2021/06/210630135027.htm

Trauma therapies that are proven to work

 The building collapse in Surfside, Florida last week killed at least 16 people, and nearly 150 remain unaccounted for, but what will become of those who survived? How will they get their lives back, and will they ever be able to go into -- much less sleep in -- a high-rise again? MedPage Today Washington Editor Joyce Frieden talked with John Markowitz, MD, professor of clinical psychiatry at Columbia University, about the therapies used to treat those who need help overcoming such traumas. Their conversation was edited for length and clarity.

Tell us a little about yourself and your work.

John Markowitz, MD: I'm a professor at Columbia University and a research psychiatrist at New York State Psychiatric Institute. I'm basically established as a psychotherapy researcher -- work I've done for years.

How do people survive something like the building collapse in Florida?

Markowitz: It depends what kind of survivor you are. It's very scary to think that one moment, the floor is solid, and the next moment it isn't. There was a quote in the newspaper from a man who said, "I looked out and there was nothing there." He opened the door to an abyss and got out just in time, apparently. It's very scary when what you consider solid suddenly isn't, and you could die.

Then there are families, next-door neighbors, the survivors of the people who actually died. And how horrible to be living in the twin building [close by] and not know whether your building is safe, although the inspectors say it is. Then there are the first responders who are sorting through the debris, looking for bodies -- all these people are affected. A major event like this stirs up major feelings.

What diagnoses do these people end up with?

Markowitz: Trauma tends to lead to one or more of several diagnoses, depending on what you came in with. So, most people when they face something horrific like this are in shock, initially, and hopefully they talk to some other people and get support; we know this is really important. And if you can process the trauma -- "I have to tell you I've just been through the most upsetting thing. Can I tell you about it?" -- you're likely to do better than if you try to keep it in and pretend nothing happened. It's hard to shrug off a catastrophe.

So different people have different responses. The most common diagnosis and response to trauma is actually depression. A lot of other people are going to develop post-traumatic stress disorder [PTSD]. You need a major trauma in order to get that diagnosis, and this is certainly bad enough. Other people will develop substance problems -- if that's your vulnerability, that's your go-to, then it's a good excuse to shoot up. So, different people have different responses and you can have more than one: you can be depressed and have PTSD, or you can have PTSD and use alcohol or drugs.

How do you care for these patients; what can you do so that they are able to go into -- or even sleep in -- a high-rise building again?

Markowitz: Different conditions require different treatments. Medication can be helpful, but when you have been through something this upsetting, you have to talk about it. And most people will do that and hopefully find a support group or talk to their family or talk to their friends, and process the trauma, and they will be resilient. They'll be really upset but they won't develop a psychiatric disorder.

A subset will develop depression or PTSD or substance and alcohol problems, and you have to treat those accordingly; usually that's principally talk therapy that's indicated, and sometimes you need medication with that. But medication alone does not usually help you deal with having been through a catastrophe. And you wouldn't want to be able to enter a high-rise building only because you were popping Valiums.

If you're a resilient person, what do you tell yourself when you enter a high-rise building after having been through this type of tragedy?

Markowitz: It is a possibility that at any moment, something fatal could happen to you if you stop to think about it, right? If you're walking down the street, a brick could fall off a facade and hit you in the head. You could catch a stray bullet. Or you could trip and fall, bang your head, and have a bleed and die. Life is fragile, if you stop to worry about it -- lots of things can go wrong. Most of the time we ignore those risks unless they're imminent. We screen out worries that don't really make sense.

What happens with PTSD is that the people who develop it tend to try to bury their feelings, to not think about what happened, because it's too upsetting. And if you try to do that -- you're saying, "I'm not going to think about this, I'm not going to think about this" -- everything starts to remind you of what you're trying not to think about. So if you see a tall building, if you see a certain light in the sky which is the time of day when you last looked at the building, if you hear a certain sound, like a siren -- lots of things are going to start to remind you of what you're trying not to think about, so it really doesn't work.

There are different ways to treat that. One is to face the reminders that you're trying to avoid; that's called "exposure therapy." If you can do that -- you say, "I'm not going near any tall buildings," but if you just go near the building, and stand there until you calm down a little bit; you think, "Well it's a tall building. I'm not going in it yet, but it's actually not falling down." And there's a difference between what happened before, and being near a tall building -- tall buildings aren't inherently dangerous, just that one was.

And so, by gradually exposing somebody to their fears, they can habituate because in general, tall buildings are not dangerous. That one was, and we still don't really know why; there may have been a sinkhole, there may have been corrosion, there are all kinds of theories right now. And we just don't know. But presumably not all tall buildings are dangerous, and so you wouldn't want to give them all up.

Exposure therapy is scary for people because you have to face the fears that you're most terrified of. But as you do that -- if you can do that -- you habituate, and you say, "Well actually it's not so scary any more. It's not a pleasant thought, but in fact, the building is still standing and I'm still standing. This building looks solid."

How long does exposure therapy take?

Markowitz: Usually that's a 10-session treatment -- 10 weekly sessions or sometimes even compressed into a couple of weeks. And that seems to help a lot. Once you get the principle, you start with the easier fears and build up to the scarier ones. After a while, people really get it, and say, "Okay, I've got my life back. I don't have to have that follow me."

It used to be thought that exposure therapy was the only way to treat post-traumatic stress disorder. We don't like dogmas like that, so we did a study at Columbia, at the New York State Psychiatric Institute, funded by the National Institute of Mental Health, comparing three different kinds of psychotherapy. One is called "prolonged exposure," which is what I described earlier, where you create a kind of hierarchy of all the things that remind you, that scare you, from the trauma, and then you systematically expose yourself to them. You get used to them and the fears subside. That's the best-tested kind of treatment.

We compared that to interpersonal psychotherapy, which is a treatment we know helps with depression and eating disorders, anxiety disorders, other things -- that had never really been tested for PTSD. Instead of having to do the exposure, which a lot of people don't like because it's scary, we focus not on the idea that you have to face the trauma or re-live the story of the trauma, but rather: what has this done to your social functioning? What has this done to your interacting with other people?

People with PTSD tend to withdraw from other people, and not to trust anything, not just tall buildings; after a while, everything feels unsafe. And yet we know that social support -- being able to talk to the people around you -- is really protective. So we did this therapy where you didn't have to face your fears at all. You just had to deal with your feelings around other people and figure out who you trust and talk to, because not everybody is trustworthy. And that worked just as well as exposure therapy, without the exposure.

The third kind was a kind of "active control" treatment called relaxation therapy. You don't really do exposure and you don't focus on interpersonal functioning, but instead you do muscle relaxation, deep breathing, and physical relaxation, the idea being that when you get anxious, you then get physically agitated. And when you're physically agitated, your heart rate goes up, your muscles tense, and that bodily sensation feeds back to the brain and says, "tense," which makes you more anxious, which makes you more tense. Relaxing the body actually breaks that cycle, and people calm down. It's not quite as strong a treatment, but that also actually helps a fair number of people. There's more than one way to get people better. And then medication too.

Do you expect to see an increase in these types of trauma cases?

Markowitz: Yes. We live in a particularly violent country with lots of shooting deaths, and so far no effective way to institute appropriate gun control, so lots of people die violently from that. COVID has wiped out 600,000 Americans so far, and there's a lot of upset and stress from that -- and deaths under terrible circumstances where you can't go to the hospital to visit your loved one, and there are no normal funerals so you can't mourn in the normal way. So, lots of problems with these things. The more trauma there is, the more people are not going to be able to tolerate it, and a percentage of people will develop psychiatric problems, including PTSD.

How should communities respond when these tragic events occur?

Markowitz: What would be good is -- and I believe this is happening in Florida -- if there's a real community response. I think one of the things that helped limit the degree of post-traumatic stress in New York after September 11 was that people really pulled together. New Yorkers were friendlier than they've ever been before or since, supporting one another and being kind to one another. The bus would wait for you instead of leaving. So community support would be a really important thing, and I believe that it's happening there -- rescue teams have come in from all over the world to try to help out. So hopefully people feel supported, and able to talk about what they're going through.

And from a medical standpoint, how should primary care doctors respond when they see patients who appear to be suffering from the aftermath of a traumatic event?

Markowitz: Primary care doctors have it rough; they have on average less than 12 minutes with a patient, and they have to cover a lot of ground in that time, so it's hard to even think about psychiatric issues. But there's a significant overlap between medical conditions and psychiatric conditions, and people who are depressed are less likely to take care of themselves and take their other medications. So it's important to pay attention to your patient's state of mind.

If somebody looks really depressed, it's something to take very seriously and it's a very treatable condition, although people with depression often feel untreatable and hopeless. There are a variety of antidepressant medications available to treat depression.

And with PTSD, people often look very controlled, and emotion-less because they're burying their feelings, so it can be a little harder to pick up in some ways; depression is usually more obvious. But there are medications like serotonin reuptake inhibitors that can help with PTSD, and certainly psychotherapy.

https://www.medpagetoday.com/psychiatry/anxietystress/93374

COVID Vaccines Put to the Test in Essential Workers

 COVID-19 vaccination with Pfizer or Moderna mRNA vaccines was effective in essential workers, preventing infection and reducing the severity of breakthrough illness, a real-world study found.

Adjusted vaccine effectiveness was 91% (95% CI 76-97%) for full vaccination (defined as 14 days or more after dose two) and 81% (95% CI 64-90%) for partially vaccinated workers (defined as less than 14 days after dose two), reported Mark Thompson, PhD, of the CDC in Atlanta, and colleagues.

Moreover, risk of febrile illness in partially or fully vaccinated participants with breakthrough illness was 58% lower (OR 0.42, 95% CI 0.18-0.98), and time spent sick in bed was about 2 days shorter compared to their unvaccinated colleagues, they wrote in the New England Journal of Medicine.

They added that while efficacy of the vaccine in preventing symptomatic infection is well known from the clinical trials, there are less data on secondary benefits, such as potential reductions in COVID-19 severity, viral RNA load, and how long viral RNA can be detected.

The HEROES-RECOVER network included healthcare personnel, first responders, and other essential workers in Arizona, Florida, Minnesota, Oregon, Texas, and Utah from December 2020 to April 2021.

Participants completed electronic surveys on sociodemographic and health characteristics at enrollment, and monthly surveys about potential exposure to SARS-CoV-2, as well as use of face masks and other personal protective equipment (PPE), including time spent using PPE. They also reported any COVID-19 symptoms they experienced, including their severity and duration.

Febrile illness was defined as fever, feverishness, chills, or a measured temperature higher than 38° C (1oo.4°F). Participants provided a weekly nasal swab and saliva specimen, regardless of symptom status. Vaccination status was reported by participants through electronic and telephone surveys, as well as direct uploads of images of their vaccination cards.

Primary outcome was time to RT-PCR-confirmed SARS-CoV-2 infection in vaccinated versus unvaccinated participants, with secondary outcomes of viral RNA load, frequency of febrile symptoms, and duration of illness in patients with COVID-19 infection.

Overall, 62% of participants were women and 72% were ages 18 to 49. They were mostly (86%) white, and 69% had chronic conditions. A third of participants were nurses or other allied healthcare personnel and 26% were other essential or frontline workers, while 20-21% were primary healthcare providers and first responders.

In total, 3,179 participants received at least one dose of mRNA vaccine and of those, 84% received both doses. There were also 796 unvaccinated participants.

SARS-CoV-2 infection was detected in 204 participants, five of whom were fully vaccinated, 11 who were partially vaccinated, and 156 who were unvaccinated; 32 whose vaccination status was unknown were excluded. Of 81 sequenced virus samples, 10 were variants of concern.

Interestingly, viral RNA was detected for less than 1 week in 75% of fully or partially vaccinated participants, but was detected for more than 1 week in 72% of unvaccinated participants.

Among participants with RT-PCR confirmed infection, 25% of fully or partially vaccinated participants reported symptoms versus 63% of unvaccinated participants. Vaccinated participants also reported about 6 fewer total days of symptoms.

Limitations to the data included the fact that an 81% vaccine effectiveness estimate for partial vaccination is based on a median of 22 partially vaccinated days. That could overestimate vaccine effectiveness if infections were not detected in vaccinated participants, due to either reduction in viral RNA load or sensitivity of PCR assays. Also, the researchers were not able to complete genetic sequencing for all viruses.

Disclosures

The study was supported by the National Center for Immunization and Respiratory Diseases and the CDC.

Thompson disclosed no relationships with industry. Co-authors disclosed other government funding and various ties to industry.

Primary Source

New England Journal of Medicine

Source Reference: Thompson MG, et al "Prevention and Attenuation of Covid-19 with the BNT162b2 and mRNA-1273 Vaccines" N Engl J Med 2021; DOI: 10.1056/NEJMoa2107058.

https://www.medpagetoday.com/infectiousdisease/covid19vaccine/93378

CureVac COVID-19 vaccine records only 48% efficacy in final trial readout

 CureVac said its COVID-19 vaccine was 48% effective in the final analysis of its pivotal mass trial, only marginally better than the 47% reported after an initial read-out two weeks ago.

The German biotech firm said that efficacy, measured by preventing symptomatic disease, was slightly better at 53% when excluding trial participants older than 60 years, an age group that is by far the most severely affected.

CureVac said on June 16 its COVID-19 vaccine, known as CVnCoV, proved only 47% effective in an initial trial read-out and that new variants had proved a headwind, denting investor confidence in its ability to take on rival shots.

That wiped billions of euros from its market value.

Wednesday's news sent U.S.-listed shares of the company 10.2% lower to $66 after the bell.

Late-stage trials of BioNTech/Pfizer and Moderna vaccines, which like CureVac's are based on mRNA technology, had efficacy rates of well above 90% across all age groups but took place when the original version of the coronavirus was dominant.

Data on their products have, however, so far suggested only somewhat weaker protection against new variants.

The CureVac study, which involved about 40,000 adult volunteers in Europe and Latin America, showed that efficacy was 77% in the age group below 60 years of age when considering only moderate to severe symptoms and excluding mild cases.

CureVac said it had sent the data to the European Medicines Agency (EMA) as part of an ongoing dialogue with the EU drugs regulator.

CureVac previously said that the regulatory hurdle was 50% efficacy in principle but that various other considerations would come into play.

"In this final analysis, CVnCoV demonstrates a strong public health value in fully protecting study participants in the age group of 18 to 60 against hospitalization and death and 77% against moderate and severe disease – an efficacy profile, which we believe will be an important contribution to help manage the COVID-19 pandemic and the dynamic variant spread," said Chief Executive Officer Franz-Werner Haas.

CureVac had registered 228 infections overall for the final analysis, after 134 cases for the interim analysis.

Public health representatives across the globe are pushing for a fast deployment of available vaccines to counter highly contagious mutations of COVID-19 such as the Delta variant that first emerged in India.

The EMA has said it would not impose a 50% efficacy threshold for vaccines and that full trial data was necessary for it to make a sound assessment on the benefits and risks of a shot.

Under CureVac's only major supply deal for the product tested in the trial, the European Union secured up to 405 million doses of the vaccine in November, of which 180 million are optional.

In a bet on CureVac's technology, Britain placed a conditional 50 million dose order in February on yet-to-be-developed vaccines that build on the product tested in the trial.

CureVac had lined up a network of manufacturing partners including Celonic Group of Switzerland, Novartis, Bayer , Fareva, Wacker and Rentschler Biopharma SE.

https://www.marketscreener.com/quote/stock/MODERNA-INC-47437573/news/CureVac-COVID-19-vaccine-records-only-48-efficacy-in-final-trial-readout-35759834/

Absci Files for IPO

 Absci Corporation ("Absci"), the synthetic biology company unlocking the potential of proteins as next-generation therapeutics, announced today that it has filed a registration statement on Form S-1 with the U.S. Securities and Exchange Commission ("SEC") relating to a proposed initial public offering of shares of its common stock. The number of shares to be offered and the price range for the proposed offering have not yet been determined. Absci has applied to list its common stock on The Nasdaq Global Market under the symbol ABSI.

J.P. Morgan, Credit Suisse, BofA Securities, Cowen, and Stifel will act as joint book running managers for the proposed offering.

https://finance.yahoo.com/finance/news/absci-announces-filing-registration-statement-194300154.html

How CRISPR gene editing will treat diseases in future: Nobel-winning Intellia co-founder Jennifer Doudna

 Gene-editing technology CRISPR reached a major milestone this past weekend, completing its first systemic delivery as a medicine to a human body.

CRISPR, or clustered regularly interspaced short palindromic repeats, effectively cuts genomes and slices DNA to treat genetic diseases.

The latest breakthrough, the result of a trial between biotech company Regeneron and Boston-based startup Intellia Therapeutics, treated a rare disease after being given as an IV infusion. Previously, other applications of the CRISPR technology had been limited to ex vivo therapy, or where cells are removed from the body for genetic manipulation in a laboratory and then reintroduced to the body.

Jennifer Doudna, who was awarded the 2020 Nobel Prize in chemistry for her work on CRISPR gene editing and is the co-founder of Intellia, recently told CNBC the evolution of the technology from the publication of her early work to clinical trials showing it to be effective in treating diseases in less than 10 years represents, “One of the fastest rollouts I think of technology from the fundamental, initial science to an actual application.”

“It’s largely because the technology comes at a moment when there’s enormous demand for genome editing, as well as a lot of knowledge about genomes,” Doudna said at the recent CNBC Global Evolve Summit in mid-June.

As for what’s next, Doudna highlighted several challenges and opportunities on the horizon for CRISPR.

Delivery of CRISPR remains a big challenge

While the technology has continued to advance, the task of getting the edited molecules to travel in the body to the cells in the areas where they are needed remains a challenge.

“This is especially an issue in clinical medicine where being able to edit brain cells, heart cells or muscle cells has incredible potential but right now we don’t really have the tools to introduce the editors into those cells,” Doudna said. “We have the editors; we just don’t know how to get them where they need to go.”

Sickle cell anemia has been an early focus

Much of the success of the applications of CRISPR thus far has been with ex vivo therapy, where extracted cells are manipulated in a laboratory and then reintroduced into a patient.

Sickle cell anemia, which is passed down genetically and affects approximately 100,000 Americans, according to the CDC, has been a particularly good target for the technology as blood stem cells can be “harvested, edited and then reintroduced to patients,” Doudna said.

Genetic diseases of the eye have also been a focus for CRISPR applications as Doudna said “it’s easier certainly to deliver to the eye than to other parts of the body.”

Delivering the edited cells to the liver has also proven to be easier thus far. “A liver is an organ that naturally takes up molecules in the body,” she said.

Any progress in eradicating the more than 100 liver diseases could have a major impact on the lives of Americans. At least 30 million people, or one in 10 Americans, has some sort of liver disease, according to the American Liver Foundation.

Focusing next on the brain, heart, muscles

The next step for innovation around CRISPR will be getting those cells to other parts of the body, such as the brain, the heart and muscles, Doudna said.

“There are some technologies already that enable some of this, for example using various kinds of viruses or virus-like particles, and I’m excited about the innovation that will come in the next few years in this regard,” she said.

The cost of treatment is a concern

But as the technology improves and scientists gain the ability to target diseases all across the body, Doudna said that for CRISPR technology to be “widely impactful,” it will need to be cheaper.

Treating sickle cell disease with CRISPR therapy, Doudna said, costs about $2 million a patient.

“That is clearly not a price point that will make this available to most people that can benefit from it,” she said.

While addressing delivery challenges may also help lower costs, Doudna said that the medical field needs to figure out how to “scale the molecule production so that we reduce costs.”

Applying CRISPR to agriculture

The advancement of CRISPR technology can also have an impact on other industries, with agriculture being one of the first to benefit.

Rather than trying to address genetic issues through breeding which can take months to years, or current methods for genetically modifying crops that have boomed in recent decades but involve inserting biological material from other species, the CRISPR technology can manipulate the genes of plants “without touching anything else,” Doudna said.

“This is opening the door to lots of things now that can be done to both address challenges of climate change, dealing with drought conditions, introducing traits in the plants that give them protection against pests,” she said.

https://www.cnbc.com/2021/06/30/how-crispr-gene-editing-will-treat-disease-intellia-founder-doudna-.html