Categories : COVIDTags :

India’s True Pandemic Death Toll Likely Over Three Million

On By ModernMedia
FIG. 1. Percentages of adults reporting daily death in household, expected percentage in 2020, and daily confirmed COVID deaths in India, 1 June 2020 to 1 July 2021. COVID Tracker deaths (red line, left vertical scale) represent COVID deaths reported daily (smoothed for rolling 7-day averages) at age 35 or older, less a subtraction value of 0.59% to represent nonhousehold reporting. Expected all-cause deaths (grey dashed line, left vertical scale) per year of 3.4% (see text), with 7-day smoothed weekly adjustment from variation observed among 480,000 deaths in the Million Death Study from 2004 to 2014. Confirmed COVID deaths (blue bars, right vertical scale) are daily reports from Covid19india.org (2).
Credit: DOI: 10.1126/science.abm5154

An updated estimate for COVID mortalities in India puts the true number at over three million, which is so much higher than the official estimate of around a million that it would raise the World Health Organization’s official global death toll by 50%.

When the COVID Delta wave hit India over early to mid-2021, hospitals were filled beyond capacity, oxygen ran out, and community networks for tending to the dead were overwhelmed. At the time, government reporting put the death toll at under a million.

However, other sources estimated that the toll was far worse than this, likely in the millions. A more accurate measure of COVID mortality in India puts that number at 3.2 million people, according to a paper published in Science. 

“The analyses find that India’s cumulative COVID deaths by September 2021 were six to seven times higher than reported officially,” the international team of researchers wrote.

“You have to put that into context,” said Associate Professor of Economics Paul Novosad, co-author of the paper. “At the time that we were writing this, India was reporting about half a million official COVID deaths, the World Health Organization was reporting about 4 to 5 million COVID deaths globally, so just this adjustment – just correctly counting the deaths in India – is going to raise the global mortality count of COVID by almost 50%.”

The team looked at all-causes mortality from an independent survey of 140 000 adults, and from two government data sources including deaths reported in health facilities and registered deaths in 10 Indian states. Comparing these to previous years without COVID, they found that total deaths increased by 26% to 29% in the COVID period compared to total deaths in past years. This range was consistent across separate data sources, the researchers wrote.

“We’re triangulating on this number from a lot of different directions and have broad agreement regarding the range that we’re finding,” said Novosad.

Novosad’s work incorporates many novel types of data, including measures of well-being generated from satellite images, data collected by government programs, and archival administrative records not previously used for policy design. His research lab, which focuses on India, has created an open source data platform to support socioeconomic research in India and the developing world.

“A large part of my research agenda is based on finding new, 21st-century data sources and mobilising them for better research and policy,” he said.

Novosad believes this work can help answer many  critical questions about how governments and organisations can respond to the global pandemic.

“The decisions you make are better if they’re based on true facts about the world. If you don’t have data, then you just have to work on stories and impressions,” he said. “We need an empirical foundation for this kind of work.”

Source: Dartmouth College

Categories : Diseases, Syndromes and Conditions GeneticsTags :

A Life-changing Genetic Cure for Sickle Cell Patient

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Sickle cell disease occurs in people who inherit two copies of the sickle cell gene, one from each parent. This produces abnormal haemoglobin, called haemoglobin S. Credit: Darryl Leja, National Human Genome Research Institute, National Institutes of Health

Jimi Olaghere, who had suffered all his life from the chronic pain of sickle cell disease, recently received a genetic cure decades sooner than he would have believed possible.

Mr Olaghere is one of the first seven sickle cell patients who received a new gene-editing treatment going through its first clinic trials in the US. “It’s like being born again,” he said, adding that it has changed his life. “When I look back, it’s like, ‘Wow, I can’t believe I lived with that.'”

Mr Olaghere, 36 said: “You always have to be in a war mindset, knowing that your days are going to be filled with challenges.”

Sickle cell disease is caused by a mutated gene that results in abnormal haemoglobin, leading to blood cells becoming more rigid and taking on their characteristic sickle shape. These malformed cells often get stuck in blood vessels, giving rise to ischaemias and an increase in cardiovascular disease risk and organ damage. Mr Olaghere may need a hip replacement due to avascular necrosis.

The disease also causes chronic pain, which he likened to “shards of glass flowing through your veins or someone taking a hammer to your joints.”

Severe pain episodes known as crises are the hallmark of sickle cell disease. For years, Mr Olaghere was hospitalised on a monthly basis. Winters worsened the problem as the cold restricted surface blood vessels, increasing the risk of blockages. He moved to a warmer city, and became a tech entrepreneur as he didn’t think any employer would be sympathetic to going to the hospital so often.

His family urged him to participate in clinical trials or receive a bone marrow transplant. However, he thought it would take too much time and instead pinned his hopes on DNA editing “in the future, probably 20 to 50 years from now”.

But in 2019 he read about a new gene editing therapy and emailed the medical team right away. When he learned he was accepted, he said it was “the best Christmas present ever”. As the pandemic hit and flights were cancelled, he was still able to make the four-hour drive for treatment appointments.
In order to genetically edit his stem cells the stem cells were flushed out of his bone marrow and into the bloodstream for collection.

“You sit there for eight hours and this machine is literally just sucking all the blood out of you,” he said.

The process left him physically and mentally drained, and still needed  blood transfusions. Mr Olaghere had to go through this process, the most difficult of all for him, four times. 

The key to the treatment lies not in correcting the genetic defect that produces the cell but rather sidestepping it by getting the body to use an alternative: foetal haemoglobin 

Ordinarily, at around 40 weeks of pregnancy, a genetic switch called BCL11A is flipped and the body starts producing adult haemoglobin – which is the only form affected by sickle cell disease. 

“Our approach is to turn that switch off and increase the production of foetal haemoglobin again, basically turning the clock back,” explained Dr Haydar Frangoul, who treated Mr at the Sarah Cannon Research Institute.

Mr Olaghere’s stem cells were sent to Vertex Pharmaceuticals’ laboratories for genetic editing. By September 2020, the engineered cells were ready to be infused into his body. “It was the week of my birthday, actually. So it was almost like getting a new life,” he recalled.

The original faulty stem cells that remained in his body were killed off with chemotherapy, and then genetically engineered replacements were infused into his body to produce sickle-free blood.

“I remember waking up without any pain and feeling lost,” he said. “Because my life is so associated with pain, it’s just a part of who I am. It’s weird now that I don’t experience it any more.'”

Dr Frangoul said that the first seven patients’ results have been “nothing short of amazing” and represented a “functional cure” for their disease.
“What we are seeing is patients are going back to their normal life, none have required admission to hospital or doctor visits because of sickle cell related complications,” Dr Frangoul said.

So far, the genetic technique has been conducted on 45 patients with either sickle cell disease or beta thalassaemia. However, the data are still being gathered.

Source: BBC News

Categories : COVID Expert OpinionTags :

An Estimated 70% of South Africans Have Had COVID

On By ModernMedia
Image by Quicknews

Writing for GroundUp, Dr Alex Welte unpacks the results of the latest blood donor survey, which suggests that some 70% of South Africans have had a COVID infection.

The South African National Blood Service (which handles the blood supply for eight provinces) and the Western Cape Blood Service have been testing some donors for Covid antibodies over the last year or so. This has contributed to our understanding of how many people have been infected by SARS-CoV-2 (the virus that causes Covid), and what proportion of infections lead to death. It may help us plan for future waves, though exactly how is complicated.

On the assumption that another wave towards the end of 2021 was nearly inevitable – but before we all heard about omicron – it was decided to perform more such testing in early November. The numbers are now out.

The headline results are:

  • Overall about 80% of black donors had previously had Covid, and 40% of white donors.
  • There is no meaningful variation between age groups and sexes.
  • This latest survey did not include Western Cape data.
  • The test used does not detect the antibodies produced in response to vaccination, so this really is an estimate of people who have been infected.

While blood donors are not perfectly representative of the country’s population, we can take into account differences between the racial breakdown of the donor population and the racial breakdown of the general population. This means that our face-value national estimate is that about 70% of people had been infected before the omicron wave hit.

Since then we’ve had the omicron wave. We would very much like to know how many people are infected now, but there’s really no simple way to derive this number. Researchers are now updating their models with this additional piece of data, and we may see some estimates soon.

With that caution, here is my back-of-the-envelope estimate:

  • Omicron seems to have little trouble infecting people who have been infected by other variants, though there is some protection from prior infection and vaccination.
  • By late last year, quite a bit more than half the population had already had a prior infection.
  • Hence, I estimate that about half of the omicron wave infections were in previously uninfected individuals.
  • Given the infection detection rate estimates from previous waves, and a number of plausible sources of possible variation in this rate, I estimate the detection rate at about 1 in 10.
  • Given the roughly 700 000 cases reported between mid November and mid February, we get an estimate of 7 million cases, and therefore 3.5 million new infections.
  • Given our population of about 60 million, this is roughly an additional 6%.
  • Bottom line: it’s not crazy to estimate that about three-quarters of South Africans have by now been infected. But I would not be surprised if serious models come up with even higher estimates.

A troubling result of the survey is that once more it shows the serious racial disparities in South Africa. I don’t know if this carried over to the omicron wave. Estimating the racial breakdown of infection after omicron depends in a complicated way on variations in housing, lifestyle, access to vaccination, and all the usual factors that shape daily life in our country.

Dr Welte helped design and implement the blood donor survey.

Source: GroundUp

Categories : Neurodegenerative DiseasesTags :

Peptide Discovery Could Halt Nerve Degeneration

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A healthy neuron.
A healthy neuron. Credit: NIH

Promising results have been found in the quest for a treatment to halt nerve cell degeneration in disorders like Parkinson’s disease, by preventing their mitochondria from breaking apart with a particular peptide.

The research, published in Brain, examined how the long axons that carry messages between nerve cells in the brain can break down, which causes increasingly worse tightening of the leg muscles, leading to imbalance and eventually paralysis, in addition to other symptoms.

Animal studies have shown it may be a problem with the mitochondria that leads to the axons breaking down or not growing long enough. Since studying human nerve cells is difficult, the researchers made use of human stem cells they modified to become nerve cells with the genetic disorder for a particular type of hereditary spastic paraplegia.

“What we found was that the mitochondria in these cells were breaking apart, what we call mitochondrial fission, and that caused the axons to be shorter and less effective at carrying messages to the brain,” study leader Prof Xue-Jun Li said. “We then looked at whether a particular agent would change the way the nerve cells function — and it did. It inhibited the mitochondrial fission and let the nerve cells grow normally and also stopped further damage.”

What this means for the thousands of people affected by this type of genetic disorder is that this peptide could prove to be useful for a drug or other therapy to stop the nerve cells from becoming damaged or possibly even reverse the course of the damage. Additionally, gene therapy could also prevent mitochondrial damage, the researchers suggested, which would provide another strategy to reverse the nerve damage.

Source: University of Illinois Chicago

Categories : Implants and Prostheses UncategorizedTags :

Recipients of Bionic Eyes Blindsided by Obsolescence

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Source: Daniil Kuzelev on Unsplash

After the manufacturer of a bionic eye ended support, hundreds of recipients of the vision-improving implants have been left without support – “literally in the dark”, as one of them put it.

IEEE Spectrum, which first broke the story, reported that Second Sight discontinued its retinal implants in 2019. The retinal implants serve as the source of artificial vision for the users.

The publication wrote that the firm’s focus is currently on developing a brain implant known as the Orion, which also provides artificial vision. However, it only offers very limited support to the 350 or so who have the now-obsolete Argus II implants.

The system consists of a camera mounted on glasses worn by the user, which transmits video to a video processing unit (VPU), which then encodes the images into arrays of black and white pixels. The VPU then relays the pixel to an electrode array behind the retina, which creates flashes of light corresponding to the white pixels. The technology has had a long and costly road from experiment to product, starting with a lab experiment in the 1990s where stimulation of a single electrode in the retina was discovered to create a visible flash of light perceived by a blind patient. It is hugely expensive, with an estimated cost of $150,000 (R2.25 million) even before the surgery and post-surgery training. 

Implantation surgery typically takes a few hours, followed by training to help users interpret the new optical input from their implants. It is not a replacement for sight; rather it is more like a new sense. Users of the system see fleeting changes of grey which some can then use to assist with basic locomotion. However, the technology is still crude and not all benefit to the same degree. While some can make out the stripes on a pedestrian crossing, others never achieve that level of ability.

The technology also comes with some risk. In the postapproval period, 17% experienced adverse events, though this was an improvement over the 40% in the preapproval period. Since the implant can interfere with MRI scans, some have had to consider removal.

IEEE Spectrum contacted a number of patients, who voiced concern over their future. One patient, Ross Doer, said he was delighted when Second Sight told him in 2020 he was eligible for software upgrades. Yet, he heard troubling rumours. When he called his Second Sight vision-rehab therapist, “She said, ‘Well, funny you should call. We all just got laid off,’ ” he recalled. “She said, ‘By the way, you’re not getting your upgrades.’ ”

“Those of us with this implant are figuratively and literally in the dark,” he said.

Second Sight, when contacted by the publication, said that it had to reduce its workforce because of financial difficulties, and though it attempted to provide “virtual support” was unable to assist with repairs or replacements.
Benjamin Spencer, one of the six patients to receive the new Orion implant, said that it was “amazing” and he was able to see his wife for the first time. But knowing what he does now about Second Sight makes him apprehensive, and plans to have his implant removed at the end of the study period.

Speaking to the BBC, Elizabeth M. Renieris, professor of technology ethics at the University of Notre Dame, in the US, described the development as a cautionary tale.

“This is a prime example of our increasing vulnerability in the face of high-tech, smart and connected devices which are proliferating in the healthcare and biomedical sectors,” she said.

“These are not like off-the-shelf products or services that we can actually own or control. Instead we are dependent on software upgrades, proprietary methods and parts, and the commercial drivers and success or failure of for-profit ventures.”

She added that in future, ethical considerations concerning such technology should include “autonomy, dignity, and accountability”.

Source: IEEE Spectrum

Categories : Cardiovascular DiseaseTags :

New Blood Thinners from Tick Saliva

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Source: Wikimedia CC0

Researchers looking for new anti-clotting drugs have discovered a unique class of medications that act as blood thinners by inhibiting an enzyme in the genes of tick saliva.

The study, published in Nature Communications, focused on novel direct thrombin inhibitors (DTI) from tick salivary transcriptomes, or messenger RNA molecules expressed by an organism. As a result of  the research, there are now new anticoagulant medications that can be developed for the treatment of patients with a variety of coronary issues, including heart attacks.

“Interest in ticks as a model for developing drugs that prevent blood clotting – [often] the cause of heart attacks and strokes – is firmly rooted in evolutionary biology,” said Professor Richard Becker, a co-author of the study.

“Analysis of backbone structures suggest a novel evolutionary pathway by which different blood clot inhibiting properties evolved through a series of gene duplication events. Comparison of naturally occurring blood clot inhibitors of differing tick species suggests an evolutionary divergence approximately 100 million years ago.”

Prof Becker and his international colleagues discovered DTIs from tick salivary transcriptomes and optimised their use as a pharmaceutical. The most potent is a key regulating enzyme in blood clot formation with very high specificity and binding capacity that is almost 500 times that of bivalirudin, a drug used during a typical nonsurgical procedure used to treat narrowing of the coronary arteries. Those minimally invasive procedures are performed in roughly 1 million persons yearly in the United States.

“Despite their greater ability to reduce the incidence of the formation of blood clots, the drugs demonstrated less bleeding, achieving a wider therapeutic index in nonhuman models,” Becker says. “The higher potency of the drug means it’s not necessary to use a lot of it in treating patients, which holds the cost of goods and manufacturing down.”

According to Prof Becker, tick saliva, as in other blood-feeding such as mosquitoes, contains pharmacological and immunological active compounds, which modulate immune responses and induce antibody production. This research leveraged an understanding of tick-host interactions and antibody formation.

“The holy grail of anticoagulant therapy has always been specificity, selectivity, efficacy and safety,” said Prof Becker. “Clinician-scientists must have the training and an environment that embraces asking questions and finding solutions, including those potential found deep within nature. An ability to both measure and adjust the drug dose and rapidly reverse its effects is particularly important for safety purposes. The next step is to complete pharmacology, toxicology, drug stability and other important regulatory steps before conducting clinical trials in humans.”

Source: University of Cincinnati

Categories : CancerTags :

New Recommendations for Earlier Breast Cancer MRI Screening

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This screening MRI detected a very small cancer (circled) in the patient’s breast.
Credit: Dr. Kathyrn Lowry

Annual MRI screenings starting at ages 30 to 35 may slash breast-cancer mortality by more than 50% among women with genetic changes in three genes, according to a study published in JAMA Oncology.

The pathogenic variants are in the ATM, CHEK2 and PALB2 genes – which collectively are as prevalent as the much-reported BRCA1/2 gene mutations. The study authors state that their findings support earlier MRI screening in these women.

“Screening guidelines have been difficult to develop for these women because there haven’t been clinical trials to inform when to start and how to screen,” said lead author Dr Kathryn Lowry.

The work was a collaboration of the Cancer Intervention and Surveillance Modeling Network (CISNET), the Cancer Risk Estimates Related to Susceptibility (CARRIERS) consortium, and the Breast Cancer Surveillance Consortium.

To arrive at their model, the researchers input age-specific risk estimates from CARRIERS involving some 64 000 women and recent published data for screening performance.

“For women with pathogenic variants in these genes, our modeling analysis predicted a lifetime risk of developing breast cancer at 21% to 40%, depending on the variant,” Dr Lowry said. “We project that starting annual MRI screening at age 30 to 35, with annual mammography starting at age 40, will reduce cancer mortality for these populations of women by more than 50%.”

The simulations compared the combined performance of mammography and MRI against mammography alone, and projected that annual MRI conferred significant additional benefit to these populations.

“We also found that starting mammograms earlier than age 40 did not have a meaningful benefit but increased false-positive screens,” Dr Lowry added.

Results from CISNET models have informed past guidelines, including the 2009 and 2016 U.S. Preventive Services Task Force recommendations for breast cancer screening in average-risk women.

“Modelling is a powerful tool to synthesise and extend clinical trial and national cohort data to estimate the benefits and harms of different cancer control strategies at population levels,” said senior author Dr Jeanne Mandelblatt.

The study projected about four false-positive screening results and one to two benign biopsies per woman over a 40-year screening span, the authors noted.

To get any benefit from genetic susceptibility-based screening guidelines, a woman would have to know beforehand that she carries the gene, yet most often a genetic test panel is done after a positive cancer result – too late for any benefit.

“People understand very well the value of testing for variants in BRCA1 and BRCA2, the most common breast cancer predisposition genes. These results show that testing other genes, like ATM, CHEK2, and PALB2, can also lead to improved outcomes,” said senior author Dr Mark Robson.

The researchers hope their analysis will aid the National Comprehensive Cancer Network (NCCN), the American Cancer Society and other organizations that issue guidance for medical oncologists and radiologists.

“Overall what we’re proposing is slightly earlier screening than what the current guidelines suggest for some women with these variants,” said senior author Professor Allison Kurian. “For example, current NCCN guidelines recommend starting at age 30 for women with PALB2, and at 40 for ATM and CHEK2. Our results suggest that starting MRI at age 30 to 35 appears beneficial for women with any of the three variants.”

Source: University of Washington

Categories : CancerTags :

Researchers Halt Aspirin Trial to Prevent Breast Cancer Recurrence

On By ModernMedia
Source: National Cancer Institute

A large randomised trial was halted after preliminary analysis found that taking aspirin after treatment for breast cancer did not reduce the risk of disease recurrence.

Laboratory studies had previously shown that aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs) reduced breast cancer growth and invasion. Non-steroidal anti-inflammatory drugs (NSAIDs) display anticancer activity through the inhibition of the COX-2 enzyme, triggering processes such as apoptosis, a reduction in proliferation and inhibition of carcinogenesis.  Several observational studies have shown a reduced risk of breast cancer mortality among regular aspirin users. 

There was a 25% higher risk of invasive recurrence in patients who took aspirin for a median of 18 months, but not statistically different from placebo (P = 0.1258). The aspirin group had an excess of all disease-related events, including death, local and distant recurrence/progression, and new primary tumours.

The results are in line with similar trials that ended while the Aspirin after Breast Cancer (ABC) trial was ongoing, Wendy Y. Chen, MD, of Dana-Farber Cancer Institute in Boston, said during a presentation at the American Society of Clinical Oncology (ASCO) Plenary Series.

“In this double-blind, placebo-controlled randomised trial, there was no benefit of aspirin 300 milligrams daily in terms of breast cancer invasive disease-free survival,” reported Dr Chen. “Although follow-up was short, the futility bound was clearly crossed. We had reached 50% of the events, and there was a numerically higher number of events in the aspirin arm. Therefore, it was unlikely that even with further follow-up there wouldn’t be any benefit associated with aspirin.”

“Although inflammation may still play a key role in cancer, it’s important to remember that aspirin may have different effects in other cancers, such as colon, or in different settings, such as primary versus secondary prevention,” she added.

Though the trial was well designed, enrolled the right population and with adequate dosing. the trial was stopped early for futility, commented Angela DeMichele, MD, of the Abramson Cancer Center at the University of Pennsylvania.

“The direction and magnitude [of the difference in events] highly preclude the possibility that there would have been a benefit with more follow-up,” said Dr DeMichele. “Although it was not statistically significant, we cannot rule out the possibility of a potential increase in breast cancer recurrence from the use of aspirin.”

“For patients and providers at this time, aspirin should not be used simply to prevent breast cancer recurrence,” she continued. “For those situations in which there are other options, decisions about aspirin use for other indications should definitely include an individualised risk/benefit discussion between physician and patient.”

The results underscore the need for prospective, randomised clinical trials to validate the effects of interventions from observational studies, she concluded.

The ABC trial involved patients under 70 with HER2-negative, high-risk breast cancer. The study randomised 3021 participants to 300 mg of aspirin daily or matching placebo for 5 years, with the primary endpoint being invasive disease-free survival. 

Dr Chen further noted that three clinical trials of aspirin or NSAID treatment ended while the ABC trial was ongoing. The Canadian-led MA.27 trial of an aromatase inhibitor plus celecoxib ended due to toxicity in the celecoxib arm. The randomised REACT trial of celecoxib in HER2-negative breast cancer showed no difference in disease-free survival after more than 6 years of follow-up.

The ASPREE trial tested low-dose aspirin on all-cause mortality in healthy older patients, and results showed a trend to increased all-cause mortality and significantly higher cancer mortality in the aspirin arm. 
During the post-presentation discussion, an audience member asked whether the results definitively ruled out a late benefit of aspirin, given that most patients had HR-positive disease wherein late relapse is not uncommon.

“It’s always frustrating when a study is closed early, and it was done in this case after we had reached 50% of the expected benefits,” said Chen. “There was an increase [in clinical events]. Not a statistically significant increase, but it was bordering on statistical significance. In order for aspirin to have a benefit, it would mean that in the second half, there would need to be a significantly decreased risk. It would basically need to flip and that would be biologically difficult to imagine.”

“I think it’s fair to say that this study doesn’t say definitively that there’s harm, but as for the likelihood of a benefit of aspirin, that would be extremely unlikely,” she said.

Source: MedPage Today

Categories : Diseases, Syndromes and ConditionsTags :

In MS, Twin Study Reveals Disease-causing T Cells

On By ModernMedia
Source: Pixabay CC0

By studying the immune system of pairs of monozygotic twins to rule out genetics in cases of multiple sclerosis, researchers may have discovered a smoking gun: precursor cells of the disease-causing T cells.

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system CNS and the most common cause of neurological impairment in young adults. In MS, the patient’s own immune system attacks the CNS, resulting in cumulative neurological damage. The cause of MS still unclear but a variety of genetic risk factors and environmental influences have already been linked to the disease.

Genetics have already been found to be a necessary condition for developing multiple sclerosis. “Based on our study, we were able to show that about half of the composition of our immune system is determined by genetics,” said Florian Ingelfinger, a PhD candidate at the UZH Institute of Experimental Immunology. The study shows that these genetic influences, while always present in MS patients, are not on their own sufficient to trigger multiple sclerosis. In the study, 61 pairs of monozygotic twins where one twin is affected by MS whereas the co-twin is healthy were examined. From a genetic point of view, the twins were thus identical. “Although the healthy twins also had the maximum genetic risk for MS, they showed no clinical signs of the disease,” said Lisa Ann Gerdes.

With this cohort of twins, the researchers were  tease out environmental differences. “We are exploring the central question of how the immune system of two genetically identical individuals leads to significant inflammation and massive nerve damage in one case, and no damage at all in the other,” explained Professor Burkhard Becher, leader of the research team. Using identical twins let the researchers block out the genetic influence and focus on the immune system changes that were ultimately responsible for triggering MS in one twin.

The researchers harnessed state-of-the-art technologies to describe the immune profiles of the twin pairs in great detail. “We use a combination of mass cytometry and the latest methods in genetics paired with machine learning to not only identify characteristic proteins in the immune cells of the sick twin in each case, but also to decode the totality of all the genes that are switched on in these cells,” Florian Ingelfinger explained. 

“Surprisingly, we found the biggest differences in the immune profiles of MS affected twins to be in the cytokine receptors, ie the way immune cells communicate with one another. The cytokine network is like the language of the immune system,” said Ingelfinger. Increased sensitivity to certain cytokines leads to greater T cell activation in the bloodsteams of patients with multiple sclerosis. These T cells are more likely to migrate into the CNS and cause damage there. The identified cells were found to have the characteristics of recently activated cells, which were in the process of developing into fully functional T cells. “We may have discovered the cellular big bang of MS here – precursor cells that give rise to disease-causing T cells,” said Prof Becher.

“The findings of this study are particularly valuable in comparison to previous studies of MS which do not control for genetic predisposition,” said Prof Becher. “We are thus able to find out which part of the immune dysfunction in MS is influenced by genetic components and which by environmental factors. This is of fundamental importance in understanding the development of the disease.”

The study findings were reported in Nature.

Source: University of Zurich

Categories : Regenerative MedicineTags :

Regenerating Bone with Messenger RNA

On By ModernMedia
Photo by Cottonbro on Pexels

Researchers have developed new way to get bone to regenerate with messenger RNA, which promises to be cheaper and less expensive while having fewer side effects than the current treatment.

Although fractures normally heal, bone will not regenerate under several circumstances. When bone does not regenerate, major clinical problems could result, including amputation.

One treatment is recombinant human bone morphogenetic protein-2, or BMP-2. However, it is expensive and only moderately effective. It also produces side effects, which can be severe.

Researchers at Mayo Clinic, along with colleagues in the Netherlands and Germany, may have a viable, less risky alternative: messenger RNA. 

A study conducted on rats and published in Science Advances, shows that messenger RNA can be used at low doses to regenerate bone – and without side effects. The resulting new bone quality and biomechanical properties are also superior to that of BMP-2. Additionally, messenger RNA is a good choice for bone regeneration because it may not need repeat administrations.

Human bone develops in one of two ways: direct formation of bone cells from mesenchymal progenitor cells, or through endochondral ossification, in which cartilage forms first and then converts to bone. The BMP-2 therapy uses the former method, and the messenger RNA approach uses the latter. In general, the researchers say their work proves that this method “can heal large, critical-sized, segmental osseous defects of long bones in a superior fashion to its recombinant protein counterpart.”

Further studies are required in larger animals than rats before any translation can be considered for clinical trials.

Source: Mayo Clinic