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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Affordable Care Act to Cover Breast Cancer Risk Reduction Drugs

On the heels of a new recommendation from the United States Preventive Services Task Force (USPSTF), and in line with the Affordable Care Act’s coverage of prevention services, the federal government has announced that beginning in September most health insurance plans will be required to provide breast cancer risk reduction medications free of charge to high-risk women.

 Two drugs, tamoxifen and Evista (raloxifene), are offered for breast cancer risk reduction, also known as chemoprevention. These medications can reduce the risk of invasive breast cancer by about 40 to 50 percent—but not without potential side effects. Both drugs increase the risk of blood clots, and tamoxifen increases the risk of uterine cancer.

The USPSTF recommendation, published in the Nov. 19, 2013, Annals of Internal Medicine, advises doctors to discuss chemoprevention with high-risk patients for whom the drugs’ potential benefits outweigh their risks.

Currently, only a small number of high-risk women choose chemoprevention. A study published in the February 2010 Cancer Epidemiology, Biomarkers & Prevention by Erika Waters, a psychologist at the School of Medicine at Washington University in St. Louis, and her colleagues found that close to 121,000 U.S. women who had not had breast cancer were taking tamoxifen in 2000 for risk reduction. By 2005, the number had dropped to about 51,000. Yet based on data from the National Health Interview Survey, Waters found that 10 million U.S. women would have been classified as eligible for tamoxifen in 2000—and for 2.4 million of these women, the benefits of the drug would have outweighed the risks.

The USPSTF recommendation has the potential to increase the number of high-risk women who choose to take tamoxifen, says Waters, “but maybe not in the way people expect. I think what the recommendations will do is alert clinicians and primary care physicians to the availability of the drugs, which [might then] make them more likely to offer the treatment to a high-risk woman.”For women considering whether to take these drugs, she says, the USPSTF recommendation is likely to have some weight, but “it will be only one of many factors women consider.” Similarly, she says, while the ACA coverage may help low-income women who have already decided to take tamoxifen or Evista, “just because it is free is not going to change someone’s mind if they are worried about the side effects.”

Waters also stresses the need to put the benefit of chemoprevention in perspective. “Tamoxifen can reduce risk of developing invasive breast cancer by 50 percent, and it is estimated that about one-third of postmenopausal women would be eligible to take it,” she says. “But … physical activity, not gaining weight, and losing weight if overweight can also reduce breast cancer risk up to 50 percent.” There are other ways to reduce breast cancer risk beyond taking medication, Waters says, and it’s important for health care providers to tell women about these options so that they can take them into consideration when thinking about their treatment decisions.

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Cancer Risk Reduction and the ACA

Under the Affordable Care Act, most health care plans will cover preventive services without requiring a copay or coinsurance, even if you have not met your annual deductible. This includes cancer prevention and screening services such as:

• Alcohol misuse screening and counseling
• Breast cancer chemoprevention counseling and treatment for high-risk women
• Breast cancer genetic counseling for high-risk women
• Cervical cancer screening
• Colorectal cancer screening
• Human papillomavirus (HPV) vaccination
• Mammography
• Obesity screening and counseling
• Tobacco use screening and cessation interventions

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Investigating a Novel Combination of Treatments for MS Patients

Frequently utilized MS treatments are prescribed with the goal of disease stabilization. However, they may share a common deficiency: lack of effectiveness in addressing many of the symptoms associated with the disease. Additionally they may lead to a troubling array of side effects which in themselves can negatively impact quality of life.

Newer treatments are now being investigated that seek to address many of the most debilitating symptoms related to MS. Since these novel therapies do not involve long-term treatment with pharmacological agents, they present a possible option for MS patients who are either unable to tolerate the side-effects of MS medications or who are unsatisfied with the results of their current therapies.

Dr. Michael Arata of Autonomic Specialists in Newport Beach, California has been investigating a therapeutic approach that targets many of the more troublesome symptoms suffered by MS patients, particularly those related to autonomic dysfunction (including brain fog, fatigue, headaches upon awakening, bladder and bowel problems, and inability to thermoregulate). This endovascular therapy, called Transvascular Autonomic Modulation (TVAM), has been shown to improve symptoms in a majority of patients, according to research published in Acta Phlebologica.

More recently, Dr. Arata has been investigating a surgical treatment involving the use of adult mesenchymal stem cells in conjunction with the Cell Surgical Network. This treatment involves mesenchymal stem cells in a stromal vascular fraction (SVF) that is produced from the patient’s own fat cells (extracted via a mini-liposuction procedure).

Mesenchymal stem cells and growth factors contained in SVF are known to have strong anti-inflammatory properties. Mesenchymal stem cells also have the capacity to remain dormant until they reach an area of injured or damaged tissue.

Now Dr. Arata is investigating an approach for patients with MS that includes both TVAM therapy and the SVF/mesenchymal stem cell treatment in a single outpatient visit.

It is possible that including both mesenchymal stem cell therapy and the TVAM procedure may lead to an enhanced effect. Therapeutic synergy might be achieved through both the anti-inflammatory effects of the SVF and the reparative capabilities of mesenchymal stem cells along with enhanced autonomic function seen in patients following TVAM.

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Dr. Arata responds personally to Facebook comments between the hours of 3:30-5pm PST on Thursdays and throughout the week as his schedule permits.

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Diabetes Drug Metformin May Lower Glaucoma Risk

The diabetes drug metformin was linked to a lower risk of developing the eye condition glaucoma in a new study.People who took the most metformin during the 10-year study period had a 25 percent reduced risk of glaucoma compared with people not taking the drug, researchers found.

“Glaucoma is a leading cause of blindness worldwide and classic open-angle glaucoma develops in late middle age or late age. So we hypothesized that a drug that mimics caloric restriction, such as metformin, might reduce the risk of glaucoma,” said lead researcher Julia Richards, a professor of ophthalmology and visual sciences at the University of Michigan in Ann Arbor.

Exactly how metformin might reduce the risk of glaucoma isn’t known, the researchers said. And, while this study found an association between metformin use and lower glaucoma risk, it wasn’t designed to prove a cause-and-effect relationship.Dr. Mark Fromer, an ophthalmologist at Lenox Hill Hospital in New York City, explained that glaucoma is caused by too much fluid in the eye, when fluid doesn’t drain adequately, or when the blood vessels in the optic nerve are damaged. “Somehow metformin is affecting one of those conditions,” he said.Fromer pointed out that although the results of this study are impressive, using metformin to prevent or treat glaucoma in non-diabetic patients is problematic. Metformin could drop blood sugar too low in people without diabetes, he said.

“People without diabetes should not be taking metformin,” he said. “If not monitored carefully by a doctor, it can have significant consequences,” said Fromer, who was not involved with the study.Richards, however, said that it might be possible to use metformin as a treatment for glaucoma even in people without diabetes.“But since this study was done in a diabetic population, the conclusions are currently limited to this population,” she said. “Further work, such as a clinical trial, would be needed to tell if this could be extended to non-diabetic populations or used to prevent progression of glaucoma in those who already have the disease,” Richards said.The study was published online May 28 inJAMA Ophthalmology.

For the study, Richards and colleagues collected 10 years of data on more than 150,000 people with diabetes. All were 40 or older at the start of the study. The investigators found that 4 percent of the participants developed glaucoma.The researchers said that people taking the highest amount of metformin (more than 1,110 grams in two years) had a 25 percent reduced risk of developing glaucoma compared with those not taking the drug.For every 1-gram increase in metformin taken, the risk was reduced by 0.16 percent. The researchers estimated that taking a standard dose of metformin (2 grams per day) for two years would reduce the risk for glaucoma by 21 percent.This risk reduction was seen even after accounting for lower blood sugar levels, the study authors said. Other diabetes drugs were not associated with reduced risk of glaucoma, they added.

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WHO draws lessons from Ebola to prepare roadmap for future epidemics

The World Health Organization (WHO) has concluded a meeting on Ebola R&D to look at lessons learned from the outbreak and develop a roadmap for future epidemics. Dr. Marie-Paule Kieny, WHO assistant director-general for health systems and innovation, said the Geneva meeting aimed to “come up with a new framework for R&D for diseases with epidemic potential and other health threats, so that next time we can be better prepared, faster and more effective.” Kieny said, “If something like Ebola ever happens again, the world needs to be ready with a blueprint for an R&D preparedness plan with clear rules, platforms for information sharing, established processes to expedite development and clinical trials—to activate coordinated action and limit the damage.” The meeting in Geneva, Switzerland, took place as an independent panel of experts tasked to assess the UN global health agency’s response to the Ebola outbreak in West Africa concluded in a report that “at present, WHO does not have the operational capacity or culture to deliver a full emergency public health response” and urged investments by its member states to make it fit for purpose. “Ebola is not the only epidemic-prone disease for which there are no medicines, vaccines or diagnostics. Nor is this the first time the world has been caught unprepared in the face of an epidemic,” said Kieny. “With more frequent travel, globalized trade and greater interconnectedness between countries, disease outbreaks that once used to be localized and quickly extinguished now have a much greater chance of spreading more widely. Therefore, we as a global community need to be prepared for such a possibility in the future.” To date, the Ebola outbreak in West Africa has affected more than 26,000 people and left some 11,000 dead. Dr. Margaret Chan, WHO director-general, said the Ebola R&D effort has mobilized people, institutions and resources in ways never before seen in an “otherwise horrific human calamity” and noted that the world was “likely very close to having a vaccine that can protect against Ebola.” Kieny said that thanks to “this joining of forces from all corners of the world and different sectors accelerating all actions, we now have commercial diagnostics to detect Ebola, and at least two possibly effective vaccines. These results would normally have taken five to 10 years. All this was done in less than 10 months. Even as Ebola wanes and some of the R&D efforts may not reach the goals aspired, the pioneering work done so far can be leveraged to put in place standards and best practices to improve expedited data and results sharing.”

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Pfizer launches $3M grants program to further breast cancer research

Pfizer has launched a competitive, peer-reviewed grants program to support clinical research projects investigating Ibrance (palbociclib) in advanced breast cancer.

The multi-year program, which will award a total of up to $3 million in grants to investigators in the U.S., is an extension of Pfizer’s Advancing Science through Pfizer Investigator Research Exchange (ASPIRE) initiative. It is the first ASPIRE program to focus on breast cancer research.

Ibrance received accelerated approval by the FDA in February 2015 for use in combination with letrozole for the treatment of postmenopausal women with estrogen receptor-positive, human epidermal growth factor receptor 2-negative (ER+/HER2-) advanced breast cancer as initial endocrine-based therapy for their metastatic disease.

“We believe the ASPIRE Breast Cancer Research Awards will contribute important information to our body of knowledge about the role Ibrance plays in the treatment and clinical management of advanced breast cancer, and will complement the robust clinical development program we have ongoing,” said Dr. Julia Perkins Smith, senior medical director, U.S. breast cancer lead, Pfizer Oncology. “Through these awards, we also look forward to supporting the mission of the ASPIRE program to further academic research and nurture the career development of emerging investigators in a disease area of high unmet medical need.”

Grantees will be selected through a competitive application process overseen by an independent review panel of breast cancer experts.

The review panel encourages investigators (with a special interest for emerging researchers at assistant professor level or equivalent) to submit applications for innovative research in several areas. Highlights of the research of interest include:

• Improving the medical knowledge of palbociclib in the treatment of advanced breast cancer
• Optimizing clinical management during palbociclib treatment that addresses or improves patient compliance and convenience and/or patient reported outcomes.

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SIMPLE MISTAKE MADE IN STUDY LEADS TO SEX BIAS BREAKTHROUGH IN MULTIPLE SCLEROSIS.

An innocent mistake made by a graduate student in a Northwestern Medicine lab (they accidentally used male mice instead of female mice during an experiment) has led scientists to an exciting breakthrough that offers new insight into why women are more likely than men to develop autoimmune diseases such as Multiple Sclerosis (MS).  The data finding focuses on a type of white blood cell, the innate lymphoid cell, that exhibits different immune activities in males versus females.

The team state that MS is a disease that affects the brain and spinal cord and is the result of a dysregulated immune response. Using a mouse model of MS in which only females get disease, this study showed that innate lymphoid cells are activated and protect male mice from the disease. Although female mice have these same cells, they remain inactive and do not protect them.  They go on to add that the research opens up new avenues for investigation into sex-determined disease susceptibility and could one day lead to better therapies for both men and women with MS and other autoimmune diseases.

Women are three to four times more likely than men to develop MS, and much of the current research focuses on this fact, states the researchers.   Now, thanks to a serendipitous moment in the laboratory, the team say they are investigating why males are protected from MS.  They hypothesize that understanding the mechanisms that limit disease in men can provide information that could be used in future therapy to block disease progression in women.

Like most laboratories that study the mouse model of MS, female mice are used in almost all of the  experiments.  Previous studies have shown that when the disease is induced in this strain of female mice, virtually 100 percent of them get very sick.  Male mice either got no disease or very little, so MS researchers typically use females in their studies.

A few years ago the team ran an experiment using two groups of female mice. One group was normal; the other had a genetic mutation in a growth factor receptor (c-kit) that prevented the development of a subset of immune cells.  Previous experiments from the team showed that female mice with the mutation didn’t get as sick as normal mice, and the researchers were looking into reasons why. However, instead of using females, the graduate student accidentally chose male littermates from each group.

The results of the previous study were striking; the male mice with the mutation got very, very sick.  Because this strain of male mice never get very sick, the researcher at first thought there was some sort of mistake and repeated the experiment.  The results were the same, the team realized that the mutation was behaving differently in males and females.   The team decided to investigate these findings further.

The current study shows that mice with the c-kit mutation lacked type 2 innate lymphoid cells. These cells are normally present in bone marrow, lymph nodes and the thymus of both males and females. The researchers think that in males these cells produce a protein that may help to protect from the disease by interfering with the damaging immune response.

The data findings show that when these cells are missing in the males with the mutation, that changes the whole immune response of the male animals and causes this lack of protection.  The researchers are now looking at what activates these cells preferentially in males and not in females. The next question is can the innate lymphoid cells in females be activated to decrease disease susceptibility.

The team note that this isn’t the first sex difference study in the field of MS research. In the 1990s, scientists found that testosterone was a protective hormone for women with MS, but long-term treatment of women with MS with testosterone is not a viable option because of undesirable side effects.

Type 2 innate lymphoid cells have been well studied in allergy, where they are thought to promote allergic inflammation, state the team. However, this is the first study to show that these cells exhibit sex differences in their activity and actually can protect in autoimmune disease. Early trials are underway with the researchers hoping to find clues to explain potential activators of these cells and whether those activators can be used in therapy.

The team surmise that the data findings could lead to a new approach to designing drug therapy that modulates instead of completely suppresses the immune system of MS patients, shifting the response to one that is not so damaging.

They conclude that the hope is to target these cells in a sex-specific way and provide a therapy with fewer side effects.  This early research may have implications for understanding other diseases such as lupus and rheumatoid arthritis, which also show a female bias.

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Source:  Northwestern University

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Canadian-made Ebola vaccine starting clinical trials in humans

Health Minister Rona Ambrose said trials are moving at “unprecedented speeds,” but critics slam government for not acting faster amid deadly outbreak.Clinical trials are now starting for an experimental made-in-Canada Ebola vaccine amid growing global concern over the disease that’s left more than 4,000 people dead.Federal Health Minister Rona Ambrose called the trials “promising news” in the fight against the largest-ever Ebola outbreak. As part of a process Ambrose said is moving at “unprecedented speeds,” results of the first phase are expected in December, and the hope is the vaccine can be deployed shortly thereafter.At this time, however, it’s unclear if the vaccine will ever reach people on the ground in West Africa — and critics say the trials didn’t happen nearly fast enough.

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“This is a shameful delay,” said Amir Attaran, a University of Ottawa professor and Canada Research Chair in law, population health, and global development policy. “The competing vaccine is way ahead of where we are, and that worries me,” he added. That second experimental vaccine is being produced by pharmaceutical giant GlaxoSmithKline alongside the U.S. National Institute of Allergy and Infectious Diseases, and human trials have already started in Africa. The Canadian vaccine — which many scientists consider the more promising of the two — was developed by researchers at the Public Health Agency of Canada’s National Microbiology Laboratory. Ambrose said it has been “100-per-cent effective” in preventing the spread of the Ebola virus when tested on animals. The Canadian government owns the intellectual property associated with the vaccine and has licensed the rights to a small American company, NewLink Genetics, through its subsidiary BioProtection Systems. The first phase of human clinical trials will be conducted in a lab in Silver Spring, Md., and will test the vaccine on a small group of healthy people to assess its safety, help determine proper dosage levels and identify any side-effects. “We currently have the two vaccines that are being tested and this has created sort of a ‘space race’ to find out which vaccine is going to be the first to the finish line,” noted Toronto-based microbiologist Jason Tetro. “If one of the two vaccines is slow in advancing to trials, you’ve taken a two-horse race and you’ve made it a one-horse race,” added Attaran. He said researchers need to generate data on both vaccines as soon as possible to know which one works best — or works at all. Tetro said he appreciates the need for proper protocols when it comes to clinical trials, but he would have liked to see them happen faster.

“The fact is that we really started to be concerned about this probably four months after we should have,” he said. “And it really wasn’t until somebody … appeared on North American soil with the Ebola virus that it really took off.” By the time it became clear that a vaccine would likely be needed, it was too late to prevent the high numbers of cases and deaths, he said. There have been at least 8,400 cases of Ebola, according to the latest available numbers from the Centers for Disease Control and Prevention. Toronto emergency department physician Dr. Brett Belchetz said the Canadian vaccine’s clinical trials have been greatly accelerated when compared to typical clinical trials that may take months or even years. But he said people shouldn’t be overly hopeful about the vaccine’s potential.

“Right now, all we have are animal trials that were successful,” he said, adding there are hundreds of examples in medical literature of drugs and vaccines that were successful in animals but didn’t work for humans. But Ambrose said if this Ebola vaccine is shown to be safe and effective, “it will stop this devastating outbreak.”

“This is an excellent step towards not only putting an end to the current Ebola epidemic, but also possibly preventing all future epidemics,” noted Tetro. Dr. Gregory Taylor, Canada’s chief public health officer, stressed that no one will be at risk of contracting Ebola during this first phase of clinical trials. “The vaccine does not contain any live Ebola virus,” he said.Around 40 volunteers will be taking the vaccine and will be monitored by public health professionals for any side-effects, he said. They will also be assessed to see how well their immune systems are producing antibodies against Ebola.Taylor explained that when a person takes a vaccine, “it prompts their immune system to start making antibodies” to find and neutralize foreign objects such as viruses.

Monday’s announcement of the Canadian vaccine trials came as two patients at separate Ontario hospitals awaited Ebola test results while in isolation. One patient at Ottawa Hospital’s General Campus was “under investigation” Monday after displaying Ebola-like symptoms, but tests came out negative. That patient recently visited a West African country, according to a city of Ottawa press release.Another patient at Belleville General Hospital was also being tested for the virus. Quinte Health Care spokesperson Susan Rowe stressed that it’s “highly unlikely” the patient, who recently entered Sierra Leone, is actually carrying the virus.Health Canada said there have been no confirmed cases of Ebola in Canada.

But south of the border, a Texas health-care worker tested positive for the virus after caring for an Ebola patient who later died; in Spain, a nursing aide who contracted Ebola remains in hospital.

“I think most of us working in health care are quite afraid at this point,” Belchetz said. Various countries, including Canada, have been ramping up airport screening in major cities in an attempt to detect passengers carrying Ebola.Not all are in favour of this practice. “Airport screening is essentially useless,” said Belchetz, adding passengers could fly before knowing that they’re sick.But Tetro applauded the screening initiative. “Does that mean they’re going to find anyone? No … but it shows that the system is there,” he said.

Tetro said that screening creates a chain of communication and a record of the person’s interaction at the airport, which could prove useful if they later show up at a health-care facility with Ebola symptoms.Alongside domestic protection measures, Ambrose noted the Canadian government has committed more than $35 million in various forms of overseas Ebola aid, including a shipment of personal protective equipment last week. This shipment has now arrived in West Africa.

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New portal showcases Canadian clinical research capabilities

Ottawa, ON – The Canadian Clinical Trials Coordinating Centre (CCTCC) has launched the Canadian Clinical Trials Asset Map, a pan-Canadian database showcasing Canada’s clinical research capacities.

Intended to help Canada regain its position as a leading destination for clinical trials, the online portal provides a comprehensive picture of Canada’s clinical research assets with details on clinical trial sites, research networks, research ethics boards, institutions/hospitals and individual clinical research experts.

The CCTC says it offers tremendous marketing benefits to clinical research organizations and investigators and will allow clinical trial sponsors to place trials effectively and efficiently reducing clinical trial start-up times. In addition, it is bilingual, free to use, easy to search, comprehensive and regularly updated. A forthcoming update will allow users to search by federal riding boundaries.

“The CCTAM is an important tool for enhancing Canada’s competitiveness for clinical research. The availability of this resource will simplify the study feasibility process by quickly identifying suitable clinical trial sites in Canada,” said Dr. Shurjeel Choudhri, senior vice president and head, medical and scientific affairs, Bayer Inc. “It will also be a valuable tool for highlighting Canada’s clinical research capabilities to our global organizations.”

The portal can be accessed at  www.base.cctam.ca/.

CCTCC itself was launched in April 2014 and is a partnership between the Canadian Institutes of Health Research (CIHR), Canada’s Research-Based Pharmaceutical Companies (Rx&D) and HealthCareCAN. It has the overall goal of improving the coordination of clinical trial activities and streamlining regulatory processes for companies and researchers.

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