Gut enzymes convert donor blood to much-needed universal type O

TORONTO — Canadian researchers believe they have found the means to convert any type of blood into universally usable group O with enzymes found in the human gut — a finding that could expand the pool of potential blood donors and make blood-matching easier and safer.

For transfusions to be safe, blood from a donor — for instance, A, B or AB types — must match that of a patient. O-type blood can be transfused into anyone and is always in high demand.

"Blood type is determined by the presence of antigens on the surface of red blood cells; type-A blood has the A antigen, B has the B antigen, AB blood has both antigens and O blood has none," said lead researcher Stephen Withers, a professor of chemistry and biochemistry at the University of British Columbia.

"Antigens can trigger an immune response if they are foreign to the body, so transfusion patients should receive either their own blood type, or type O to avoid a reaction," he said. "That's why O blood is so important."

Withers said the UBC team sampled DNA from millions of microorganisms found in various environmental samples to find one in which the desired enzymes might be found.

The researchers then turned their attention to the mucosal lining of the human gut — which contains sugars similar in structure to blood antigens — by extracting bacterial DNA from fecal samples.

"By homing in on the bacteria feeding on those sugars, we isolated the enzymes the bacteria use to pluck off the sugar molecules," said Withers, adding that researchers then used E. coli bacteria as "little factories" to produce quantities of the enzymes "and found that they were capable of performing a similar action on blood antigens.

"So we just simply add them to the red blood cells, they attach themselves to the surface of the red blood cell and then they cut the sugar off," he said Wednesday in an interview from Boston, where the research was presented at this week's American Chemical Society annual meeting.

Scientists have been studying the use of enzymes to modify blood since 1982, said Withers. "However, these new enzymes can do the job 30 times better."

The UBC team focused on transforming A-type blood into O-type. Enzymes to snip sugars off the surface of B-type blood cells had already been identified, so using both groups of enzymes together could convert AB blood to O, he noted.

Withers and his colleagues plan to apply for a patent on the newly identified enzymes and are set to work with Canadian Blood Services and the Centre for Blood Research to test them on different types of blood from a variety of donors.                 

"The next step is very much all about safety," he said. "There are further tests we need to do to make sure that in the process we've not inadvertently changed anything else on the red blood cell surface which could be deleterious to its function."

One advantage of these enzymes is that they work in whole blood, not just components of blood, meaning that donations could be quickly converted to universal type O, he suggested.

"So I could imagine that what could happen is it could be added to blood when it's donated and just left sitting there to do its conversion while this stuff is being stored."

Canadian Blood Services said 46 per cent of Canada's population has group-O blood, while 42 per cent is group A, nine per cent group B, and three per cent group AB.

"One of the main challenges with maintaining an adequate blood supply in developed countries is that the use of group O is not in proportion to the incidence of that blood group in the population," said CBS chief scientist Dr. Dana Devine, who called the blood-converting enzymes a potential "game-changer."

"This imbalance arises because group O blood can be transfused to any recipient and is used to treat patients in emergency settings when there is no time to determine the patient's actual blood type," she said in a statement. While it would be unnecessary to modify all non-O blood units, Devine said the technology will be important in settings where there are anticipated shortages of group O, including Canadian summers marked by increased motor vehicle accidents, as well as hurricane season in the Caribbean and troop deployments to combat zones.

Expanding global blood supply is critical in light of growing populations and the frequency of natural disasters, Withers agreed.

Sheryl Ubelacker, The Canadian Press

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Dutch medical trial using Viagra stopped after 11 babies die

A Dutch trial with the drug best known under the brand name Viagra, has been immediately halted after 11 babies of mothers using the medication died, one of the participating hospitals said on Tuesday.

When the trial was stopped on Monday, roughly half of 183 pregnant women participating were taking sildenafil, the Amsterdam University's Academic Medical Centre (AMC) said.

A similar Canadian study has been halted because of the Dutch findings, although the researchers say there have been no negative side effects reported in that study. 

A professor at the University of British Columbia confirmed 21 Canadians have been taking part in the trial. They were recruited in 2017 under Health Canada approval, with funding from the Canadian Institutes of Health Research.

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The Canadian trial's principal investigator, Dr. Ken Lim, said all three recruiting sites in Canada have been suspended.

"We are not aware of an increase in adverse outcomes," among the Canadian participants," Lim said in a statement.

"We contacted the one Canadian woman who was currently in the trial, directing her to stop taking the drug or placebo."

The Dutch study started in 2015 and involved 11 hospitals. It was designed to look at possible beneficial effects of increased blood flow to the placenta in mothers whose unborn babies were severely underdeveloped.

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Around 15 women who took the medication have not yet given birth.

"Previous studies have shown that sildenafil would have a positive effect on the growth of babies. The first results of the current study showed that there may be adverse effects for the baby after birth," the AMC said.

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Yet the results showed that 17 babies were born with lung conditions and 11 died. Among the roughly equal control group, just three babies had lung problems and none died.

Among the women taking sildenafil, 11 of the babies died due to "a possibly related lung condition" that caused high blood pressure in the lungs and may have resulted from reduced oxygen levels.

'We cannot take chances'

An interim analysis found that the chance of blood vessel disease in the lungs "appears to be greater and the chance of death after birth seems to have increased. The researchers found no positive effect for the children on other outcomes," the AMC said.

Stephen Evans, a professor of pharmacoepidemiology at the London School of Hygiene and Tropical Medicine, said the small number of trials with pregnant women has limited our knowledge of medicines in pregnant women.

"There have been other studies in this area, both involving preliminary work using animals and using pregnant women, and there was no indication that the treatment was dangerous based on previous research," he said.

UBC's Lim said although there were no known negative reactions in Canada, "we cannot take any chances with the health of mothers and their infants," and researchers will look into previous studies on sildenafil.

"We are working co-operatively with our international research partners in the Netherlands, the United Kingdom, Australia and New Zealand to better understand the cause of the results in the Netherlands, and how they relate to results being reported by U.K. and other researchers, which did not indicate any evidence of harm," Lim stated.

Sildenafil was originally developed by Pfizer but is now off patent and available as a generic. Pfizer had no immediate comment.

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Boys should be given HPV jab, says vaccine committee. Here’s what happens next.

It’s nearly a decade since the human papillomavirus (HPV) vaccine was first introduced in the UK to help protect against the virus that causes most cases of cervical cancer. But until now, it has only been routinely offered to girls.Today, the Joint Committee for Vaccination and Immunisation (JCVI) recommended that adolescent boys should now also receive the vaccine.When and how this will happen is now down to the Government. But the recommendation comes from years of mounting evidence around likely health benefits and overall cost effectiveness.

HPV and cancer

HPV is a big family of viruses. There are more than 100 different types and some are more dangerous than others. While some low-risk types cause growths like warts or verrucas, there are thirteen high-risk types that are linked to cancer.HPV is very common, with 8 in 10 people infected at some point in their life. Usually our bodies clear the infection without it causing any problems. But in some cases a lasting infection can lead to cancer.This is because the virus damages the infected cells’ DNA and causes them to start dividing out of control, setting them on the road to cancer.Thanks to the vaccination programme, many people know that HPV causes cervical cancer – in fact it’s linked to all cases of the disease in the UK. But HPV is linked to other cancers too – including anal, penis and some types of mouth and throat cancer.

Why wasn’t the HPV vaccine always available for boys?

The HPV vaccine protects against 4 types of HPV. Two are linked to cancer: HPV 16 and 18, which together cause around 7 in 10 cervical cancer cases in the UK. The vaccine also protects against HPV 6 and 11, which cause most genital warts.The vaccine has been available to girls in the UK since 2008. It was initially only recommended for girls as the strongest evidence of health benefits and cost effectiveness was for cervical cancer and genital warts.Since the vaccine was introduced, we’re starting to see HPV infections in people who have been vaccinated falling. This suggests the vaccine is preventing HPV infection and, in the future, this should prevent cervical cancers.But HPV is linked to cancers in men as well as women.Men who have sex with women will get some protection from the current vaccination programme if their partner is vaccinated. The same can’t be said for adult men who have sex with men .In 2015, the JCVI, which advises UK health departments on vaccines, recommended extending vaccination to adult men who have sex with men. This group of men are at a higher risk of anal cancer. Up to the age of 45, these men can request HPV vaccination at sexual health clinics.But up until today, the programme hadn’t been recommended for boys, as the JCVI weren’t convinced it would be cost-effective.Today’s decision brings the UK in line with other countries including the US and Australia, which already offer the vaccination to boys.

Who will be offered the vaccine?

The JCVI has recommended the vaccine for boys aged 11-13, similar to the vaccination programme for girls. HPV vaccination is most effective in people who haven’t ever had an HPV infection. And as HPV is mostly transmitted through close sexual contact, vaccination is offered at a young age when people are unlikely to have had any sexual experiences.Men above the vaccination age who don’t have sex with men won’t be offered the vaccine. But it’s important to remember that most people clear HPV infections without them causing any symptoms or problems. And for most cancers linked to HPV there are also other ways to reduce your risk through things like not smoking or drinking less alcohol.

What happens now?

The recommendation for a gender neutral vaccination programme for adolescents has been years in the making. The next step is for the Government to formally accept the recommendation and extend the programme to boys.Until it does, we won’t know the details of when and how the programme will be rolled out. Once they have accepted the recommendation, the Government must publish a plan and timetable for the roll-out.This will need to be accompanied by more details on the programme itself. When the vaccine was first offered to girls in the UK, a ‘catch-up’ programme was introduced for girls up to the age of 18, and we want the Government to do the same for boys.Finally, the programme will do nothing if people aren’t aware it’s happening. We want to see a national awareness campaign to clearly communicate about the vaccine and its potential benefits, as well as new information for parents and boys.By offering the vaccine to everyone aged 11-13, the number of cases of HPV, along with the cancers they cause, could be dramatically reduced in the future.

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‘Magic’ blood test could make bone marrow transplants for blood cancer safer

A blood test could help predict the risk of complication following a bone marrow transplant in some blood cancer patients, according to a new US study.

The test could help identify which patients given a transplant are likely to develop a potentially fatal complication, the researchers report in The Journal of Clinical Investigation Insight

(link is external)

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"The test worked in different hospitals and in different groups of patients in the US and Europe, suggesting that it could be used widely" – Professor Ronjon Chakraverty, Cancer Research UK

In doing so, the test could “allow early intervention and potentially save many lives”, said lead researcher Professor James Ferrara from Mount Sinai School of Medicine(link is external). 

Bone marrow transplants, in which a patient’s blood stem cells are replaced with those from a donor, are given to some patients with blood cancer to cure their disease. But around half of patients who receive the procedure develop a serious and often fatal complication called graft-versus-host disease (GVHD). 

This happens when the donated immune cells recognise the patient’s body as a threat and launch an attack against it, causing inflammation that sometimes doesn’t respond to treatment. 

For this latest study, researchers from 11 cancer centres in the US and Europe looked at blood samples from almost 1,300 bone marrow transplant patients to see if they could predict whether a patient will develop GVHD, and also their outlook.

They developed a test, called ‘MAGIC’ (Mount Sinai Acute GVHD International Consortium), looked at four different molecules in the blood. The researchers found that measuring the levels of two of these molecules – ST2 and REG3a – just one week after the transplant procedure, could help identify those at high risk of developing the complication and dying. 

Researchers at Mount Sinai are now using these results to design clinical trials looking into whether certain immunotherapy drugs, normally given at the onset of GVHD, could improve the outlook for some patients if given earlier on, after the test identifies them as high risk. 

Professor Ronjon Chakraverty(link is external), a Cancer Research UK expert on stem cell transplants, said: “This study reveals that a blood test performed just one week following a bone marrow transplant accurately identifies which patients are at the greatest risk of this life-threatening condition. 

“Importantly, the test worked in different hospitals and in different groups of patients in the US and Europe, suggesting that it could be used widely. Tests such as this could spot patients who are most at risk, and make sure they get special targeted treatment before GVHD develops.”

References

Hartwell, M. J. et al. (2017). An early-biomarker algorithm predicts lethal graft-versus-host disease and survival. JCI Insight. 

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Smoking vaccine fails clinical trials, $4.1 million in taxpayer dollars down the drain

An experimental new anti-smoking vaccine has failed miserably in clinical trials, faring no better than a placebo shot at helping people to quit smoking.Produced in partnership with drug giant GlaxoSmithKline (GSK), Nabi Biopharmaceuticals’ NicVAX was intended to help people quit smoking by triggering the production of antibodies that would attach to nicotine and prevent the substance from reaching the brain — but the vaccine has proven to be nothing but non helpful medicine.

According to reports, the yearlong study involved 1,000 people that were given either NicVAX or a placebo shot, and who were tracked to observe smoking habits following treatment. Roughly 11 percent of patients who received the NicVAX shot quit smoking, but the same amount from the placebo group also quit smoking — in other words, there was no difference at all in quit rates between the two groups. Upon news of the failed Phase III trial, Nabi’s stock price dropped a massive 70 percent, and GSK’s dropped about one percent. But what is even more shocking is the fact that Nabi had used $4.1 million in taxpayer dollars to fund research for NicVAX. The company’s website openly discloses that the US National Institute on Drug Abuse (NIDA) had granted $4.1 million in funding to the company back in 2005 for the project.

Remember, both Nabi and GSK are private, for-profit drug companies, and GSK had a net income in 2010 of nearly $3 billion. And yet the US government decided to take Americans’ hard earned money and funnel it into a failed project that, if eventually “successful” (at least in terms of somehow gaining FDA approval, not in terms of actually working to “cure” smoking), will translate into $500 million in profits for Nabi, and possibly even more for GSK.

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Researchers discover exciting new line of stem cells by accident

The already exciting prospect of stem cell research has just got a little more exciting, with the discovery of a new line of “more robust and easily manipulated” embryonic stem cells, completely by accident.A team of researchers from the University of Missouri came across the new cell type during studies into the causes of pre-eclampsia, a rare and complex condition which affects only pregnant women. It requires emergency caesarian early on in pregnancy to save both mother and child and it’s causes are currently attributed to a variety of factors, including shallow placentas.

“We can use these new stem cells for future research to better understand how embryos are organised and what causes diseases like pre-eclampsia and other prenatal problems.” said Michael Roberts, a Curators Professor of Animal Science and a Professor of Biochemistry. “These new stem cells made us realise that embryonic stem cells exist in a number of different transitional states, and it should open the door for future stem cell research that is much more efficient.”

The stem cells, termed bone morphogenetic protein (BMP)-primed stem cells by the team, were accidentally discovered during the growth of placenta cells. As part of their study, Roberts and his colleagues were attempting to grow placenta cells from embryonic stem cells by adding a substance called BMP-4, a protein which helps define axes of growth in embryo development, for a shorter timeframe than had previously been studied. Instead of forming placenta cells, however, the stem cells grew into what was a previously unobserved state – “BMP primed”.

They found these cells were much easier to work with in the laboratory than traditional stem cells, due to easier growth and them expressing their genes in a similar way. Embryonic stem cells as a whole are of increasing interest in research, due their ability to develop into a number of different cell types such as muscle, bone or skin.

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