Critical step forward for radiotherapy with a new method to treat cancer

Critical step forward for radiotherapy with a new method to treat cancer

A new research development from The University of Manchester and the Christie NHS Foundation Trust has shown progress for developing a potential new cancer treatment using high energy electron beams.

The collaborative research team have published their findings in Nature’s journal, Scientific Reports, and demonstrated that Very High Energy Electron (VHEE) beams can have a positive effect for treatment with damage to DNA at similar levels to those conventional X-Rays and proton therapy, whilst harnessing the unique technological qualities of electron beams.

Human cells are composed of DNA and this new result is a fundamental step forward for VHEE radiation as a treatment for a number of cancers. This new treatment has the potential to extend conventional treatment with electron beams used in hospital which only penetrate a few centimeters into the body and struggle to reliably reach deep seated tumors.

This new technology has the potential to extend the toolbox of radiotherapy techniques that can be used in hospitals to treat cancer, in particular an ability to treat deep seated tumors with electrons in a robust manner.

Earlier work from The University of Manchester group indicated this radiation is insensitive to intervening media—meaning if the dimension of the lung changes for example (the patient’s breathing) then the radiation will remain targeted to the tumor, limiting the damage to healthy tissue. The results in this new paper are a first to quantify damage to Double Strands of DNA with high energy electrons.

Following experiments carried out by The University of Manchester, at CERN’s CLEAR 250 MeV facility and at Daresbury Laboratory, the findings show Very High Energy Electron (VHEE) beams are effective at causing DNA damage, important for killing cancer cells, for radiation given over the course of several minutes and for the rapidly evolving field of sub-second FLASH radiation.

In the newly published paper the research group focussed on experimentally determining the DNA Double-Strand Break yield and this was used to evaluate the Relative Biological Effectiveness (RBE)—a key value to evaluate the effectiveness of this type of radiation compared to existing radiation treatments. These results, a first in the field, were found to be consistent with established radiotherapy modalities.

Kristina Small, a Ph.D. student, carried out the experiments, Kristina said: “Electron beam treatment has been identified as a candidate for treatment of lung cancer, a cancer which sadly still has a low survival rate. We have shown, through experiments at CERN and Daresbury Laboratory that VHEEs cause a similar level of damage to DNA compared to protons and X-rays.”

Similarities in physical damage between VHEE and conventional modalities gives confidence that biological effects of VHEE will also be similar—key for clinical implementation. The researchers also made detailed Monte-Carlo (statistically based) simulations—and these complicated simulations were consistent with previous experiments.

Professor Roger Jones from The University of Manchester and Cockcroft Institute said: “This paper represents a significant step in verifying the potential of Very High Energy Electron beams to treat cancer. It relies on a seamless collaboration of The University of Manchester’s Department of Physics and Astronomy, The Division of Cancer Sciences, Daresbury Laboratory and CERN, and The Christie NHS Foundation Trust.

“It is the first to quantify both single strand breaks (SSB) and double strand breakage (DSB) in DNA using VHEE beams. To do this we used plasmids which effectively freeze the damage (as plasmids are not equipped with repair mechanisms that living cells possess) and hence enabled us to process the results obtained at CERN back at the Manchester Cancer Research Centre. These results compare well with detailed Monte Carlo simulations. It also explores the exciting regime of FLASH Radiotherapy—which entails delivering a high dose over a sub-second timescale and where early experiments worldwide show potential to spare healthy cells during treatment. This work points the way for a potential new paradigm in radiotherapy.

“Advantages of this technique over existing methods include—potentially more precise and rapid delivery to tumors with reduced fractionation (number of times the patient has to have a follow up radiation treatment) which result in fewer patient visits needed with a more conformal high dose delivered. Recent results in the area of ultra-high dose rate radiotherapy indicate considerable sparing of healthy tissue.”

The next step is to further demonstrate these exciting results in future experiments. In the long term, researchers hope that VHEE therapy will make a valuable addition to the radiotherapy toolkit in order to improve future cancer treatment.

Dr. Michael Merchant (Division of Cancer Sciences, The University of Manchester) said: “This is an exciting first measurement of DNA damage for very high energy electrons. These measurements will help to build understanding of how to harness the medical applications of very high energy electrons.”

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DR CHRIS VAN TULLEKEN: How we learned to treat Covid-19 then beat it

How we learned to treat Covid-19, then beat it! DR CHRIS VAN TULLEKEN describes the front line of a battle that humanity can’t afford to lose

The next pandemic is already in the post. This month, the authorities in Guinea in West Africa declared a new Ebola outbreak; Saudi Arabia’s health ministry has reported four new cases of MERS, a coronavirus we catch from camels, writes Dr Chris van Tulleken

As an infectious diseases doctor at the Hospital for Tropical Diseases, which is part of University College London Hospital (UCLH), I see patients with infections — and I also study viruses in the lab at University College London next door.

Yet despite my clinical and research experience, over the past year I’ve been utterly wrong about so much of this pandemic — and especially about the infection it would cause.

When I first realised in early 2020 that we were facing a global pandemic of Covid-19, I imagined that this new foe would be a virus that largely affected the lungs — a more serious version of the four coronaviruses that already circulate and cause colds.

This was the received wisdom following a very similar but far more deadly coronavirus that emerged in 2003: SARS.

That belief changed entirely last March when my twin brother, Xand, caught Covid.

His symptoms were miserable but expected: cough, fever, exhaustion and loss of smell and taste. 

He seemed to manage them well in isolation, and within a fortnight appeared to be on the road to full recovery.

But then one morning, early in his recovery, while I was working a shift on a Covid ward at UCLH, Xand came into A&E as an urgent case. 

He’d developed a dangerous heart rhythm disorder, atrial fibrillation, likely as a result of the virus inflaming his heart.

Xand had a heart rate of 170 beats per minute (it should have been around 60) and his blood pressure was low. Colleagues from the A&E and anaesthetics teams sedated Xand and cardioverted him — giving him a large electric shock to temporarily stop his heart, allowing it to restart in a normal rhythm.

It was a terrifying and, for me, tearful moment. This is a fairly routine procedure but the worst consequences are severe.

Covid is starting to make many of us wonder if contracting a virus as an adult may explain the symptoms many previous patients have been struggling with. The latest science of long Covid is just one of the topics covered in a new BBC Horizon special, to be broadcast this Thursday, that marks nearly a year since Britain first entered lockdown

Nor was this to be the last time: Xand came into the emergency room twice more as the year went on. It was clear that Covid had damaged his heart.

As this was unfolding in my own family, it was becoming clear from patients and colleagues from other specialties that Covid affects every organ system — even in those who don’t have a serious infection.

We now know from hard-won experience that it can have widespread and devastating effects, causing strokes and brain inflammation, clots and heart attacks.

And contrary to media reports, we were seeing these problems in many young and previously healthy people. A few died, but many have been left devastated by an apparently mild illness.

Xand is still taking medication to keep his heart in rhythm.

Meanwhile, other effects on the heart are still unfolding. Only last week, a study by UCL found high levels of potentially chronic heart problems among people who have survived hospitalisation with Covid — revealed in blood tests for troponin, a protein released from injured heart muscle.

The lessons learned: Doctors Chris (left) and Xand van Tulleken in a Horizon report. We now know from hard-won experience that it can have widespread and devastating effects, causing strokes and brain inflammation, clots and heart attacks

Perhaps the most worrying side-effect for younger people is long Covid — a cluster of different symptoms along with severe ongoing fatigue.

For a long time, the medical profession has been unable (and, occasionally, unwilling) to help people with fatigue syndromes such as ME (myalgic encephalomyelitis) and fibromyalgia. They often have normal test results and they can get written off.

Covid is starting to make many of us wonder if contracting a virus as an adult may explain the symptoms many previous patients have been struggling with.

Covid-19 facts

  • 10-30% of people who get Covid are responsible for 90% of further infections
  • There are 200 new Covid vaccines currently in development — 60 are in clinical trials 

The latest science of long Covid is just one of the topics covered in a new BBC Horizon special, to be broadcast this Thursday, that marks nearly a year since Britain first entered lockdown.

Presented by me, Xand and Dr Guddi Singh, a paediatrician at Guy’s and St Thomas’ NHS Foundation Trust, it features interviews from scientists and clinicians at the forefront of the fight.

We have learned so much in the past year, and now have the knowledge to end the pandemic and stop the appalling sickness and death caused both by the coronavirus and by lockdowns.

And the data we have seen seem to make some choices increasingly clear if we want to relegate this virus from a lethal pandemic to an occasional pestilence.

Here are some of the lifesaving lessons that we’ve learned. 

Genetics are key to beating pandemic 

What we know about the new coronavirus, how it behaves and how to tackle it, is the culmination of the revolution in genetics that started with the project to sequence the human genome.

In the 20 years since that was completed, we haven’t quite seen the promised benefit to us all. Until now.

The story of this pandemic — past, present and future — can be written with an alphabet of just four letters: those of the genetic code that’s common to all life.

These letters — A, T, C and G — are the building blocks of the DNA blueprint in all our cells, including many viruses. The ways in which these letters are combined in long sequences determine what makes all living things unique.

It is thanks to the advances in genetics, unimaginable even a few years ago, that we now know enough about how this virus spreads and mutates so we can actively end this pandemic and return to normal life.

What we know about the new coronavirus, how it behaves and how to tackle it, is the culmination of the revolution in genetics that started with the project to sequence the human genome

The sequence of the Covid-19 genome was published in January 2020 — astoundingly fast. This meant that by early February, Professor Teresa Lambe and the team in Oxford (working with AstraZeneca), along with other scientists around the world, were already designing the vaccines many of us have now had.

As Teresa explained when we interviewed her, the vaccines licensed in the UK are gene-based, which means they don’t need a sample of the virus to start testing and manufacturing: they just need the genetic code, which can be sent in an email. (This massively speeds up the development process as there’s no need to culture live virus.)

Genetics have also allowed us to diagnose the virus. The gold standard PCR test is a genetic test that looks for parts of the virus genome. It is highly accurate and has allowed us to understand so much of the virus biology.

Genetic technology has also enabled the Covid-19 Genomics UK Consortium (COG-UK) to track the emergence of new variants by sequencing diagnostic samples from all over the UK.

As Professor Sharon Peacock, who heads up COG-UK, told me, it is thanks to this work that we are now increasingly sure that our homegrown ‘Kent’ variant, which swept across England last November, is not just more transmissible but may also be more deadly, hospitalising a greater proportion of the patients who get it.

For a while, it had seemed like this virus changed relatively slowly — a couple of mutations a month. But not now.

We know that allowing a surge to spread through the population once the vulnerable are vaccinated will give an advantage to those variants capable of spreading in vaccinated people. People are seen in Regents Park, London

I also spoke with an old friend and colleague, Ravi Gupta, a professor of clinical microbiology at the Cambridge Institute of Therapeutic Immunology and Infectious Disease and member of NERVTAG (the body that advises the Government on new respiratory viruses).

He described his shock when he first saw the gene sequence for the Kent variant: it had not one or two but 23 different DNA mutations. He’d seen this exact pattern in a patient with a perilously weak immune system (as a result of chemotherapy for cancer) with Covid at Addenbrooke’s Hospital in Cambridge who’d been suffering with the virus for 100 days.

The patient was given ‘convalescent plasma’ from those who had recovered from Covid. The plasma contained antibodies that should, theoretically, kill the infection. Instead, the virus evolved to get around this by accumulating mutations in its DNA. By the time the patient had died, the virus had evolved 37 separate mutations.

This may be where some of the new variants are coming from — chronic cases in patients with immune dysfunction where the virus has a unique opportunity to try out different evasion strategies.

The genetic sequences that we use to diagnose patients are now also being used to build the next round of vaccines. We are going to see variants emerge around the globe, but instead of starting from scratch, the sequence can be plugged in and an updated vaccine produced in months, not years. I can’t imagine where we would have been now with this pandemic had it not been for genetics — but without doubt, we would be desperately worse off.

Vaccines get us on road to freedom 

Eventually, once as many people as possible are vaccinated, herd immunity will reduce transmission of the virus. But this will take many months — and we are a very long way off having natural immunity from the massive waves of virus that have spread.

In the meantime, reducing transmission is vital for the success of our vaccine rollout. Allowing the virus to continue to spread before widespread vaccination will not only lead to deaths and long Covid but also risks the emergence of vaccine-resistant strains.

It is a law of biology as immutable as the law of gravity that viruses mutate when they spread. Every infected person and transmission gives a chance to the virus. We know that allowing a surge to spread through the population once the vulnerable are vaccinated will give an advantage to those variants capable of spreading in vaccinated people.

We are going to see variants emerge around the globe, but instead of starting from scratch, the sequence can be plugged in and an updated vaccine produced in months, not years

Currently, our vaccines work superbly well. Surrendering an advantage to the virus by allowing it to start spreading rapidly would be a terrible waste. It will also kill many young, fit people and leave many others devastated with the consequences of infection.

Dying of Covid-19 now is like being a soldier shot dead on Armistice Day when the ink is drying on the treaty but the ceasefire is yet to begin. This is now a vaccine-preventable disease. If everyone complies with lockdown right now, that vaccine potential won’t be wasted. 

Why more patients are now surviving 

The hospital death rate from Covid has dropped spectacularly. Partly this is due to the case mix of patients (tragically, many people most likely to die have already died), but in large part it’s also due to advances in clinical care.

The high-tech solutions, especially the drugs, make the headlines — but they’re not the only thing making the difference, as I saw when I went to interview Mark Vargas, a senior charge nurse on the intensive care unit (ICU) nursing team at University College London Hospital.

I watched his team perform an emergency ‘prone’ on one of the sickest patients. This is where the patient is flipped onto their front to allow improved blood and air flow in their lungs.

Done badly, it is extraordinarily dangerous, as the ventilator tube can be pulled out. As it is such a risky procedure, in the past it was done only a few times per year, but the patient I saw flipped over while filming Horizon was the third patient expertly and safely proned that day.

Proning is just one of a huge suite of changes made in ICU so that, despite the fact that they are now looking after five patients with just two nurses (the ratio would normally be 1:1), survival rates have still improved.

We need to spot the super-shedders 

To reduce transmission and the worst effects of long Covid, it’s vital we find the people who spread the most virus and isolate them.

Scientific studies have revealed that the vast majority of people who contract Covid-19 never pass it on — and that between 10 to 30 per cent of infected people are responsible for 90 per cent of all transmissions.

This may be partly down to some people’s biology. In the Horizon programme, Mark Woolhouse, a professor of infectious disease epidemiology at Edinburgh University, refers to these people as super-shedders, because they release unusually large numbers of virus particles. 

This was starkly demonstrated in the summer of 2020, when an airliner landed in Ireland from the Middle East carrying 49 passengers.

It was later discovered that 13 were infected with Covid-19. Most of them did not go on to infect anyone else; however, five of the passengers went on to infect 43 other people.

We also know that there are super-spreader events which are crucial. If a super-shedder patient is sitting quietly at home alone, then they won’t infect anyone. But if they go to a party, say, they could infect a huge number of others present.

Super-spreader events tend to be poorly ventilated, indoor environments with lots of crowding: weddings, churches, choirs, gyms, funerals, restaurants. Loud talking or singing massively increases the risk. Clubs and pubs are prime examples.

Any case of Covid is most likely to have been infected at a superspreader event or by a super-shedder. This means that simply isolating the contacts of an infected person, as we currently do, is important — but what we would ideally do is look backwards at all the people our case may have caught it from.

This will identify the superspreader event or person and allow tracing of their contacts — which will produce many more cases who need to be isolated. This is called backward tracing and it is not trivial. It takes resources and money and needs transmission rates to be low enough to do it.

As I write, there are more than 10,000 new cases each day. It is simply not possible to trace and isolate everyone linked to every one of them.

But what is clear is that if our vaccines and our current tracing methods are going to work, we must ensure that transmission rates in the community are at rock bottom before we start to open up the places where it spreads best.

Rapidly opening up venues where large numbers of people are indoors with poor ventilation for prolonged periods may lead to the emergence of vaccine-resistant strains and another cycle of deaths from Covid, followed by lockdown.

I would rather catch Covid-19 now than a year ago. But knowing about long Covid, I would much rather not get it at all. And that is the point of continuing to drive down the daily infection numbers whilst we roll out mass vaccination and effective tracking and tracing. 

Danger of trusting in herd immunity 

When we do the maths, it looks like we will need to vaccinate many more people against Covid-19 than was previously hoped to achieve herd immunity, which will prevent the virus from spreading.

Indeed, we might have to vaccinate as many as 97 per cent of the population. This is because the new variants we’ve seen so far are significantly more contagious than the strain from China.

Certainly, we can’t rely on natural herd immunity emerging by sufficient people getting infected and surviving to develop their own immune resistance, as some mooted early on. That idea was always extraordinarily naïve and dangerous.

When we do the maths, it looks like we will need to vaccinate many more people against Covid-19 than was previously hoped to achieve herd immunity, which will prevent the virus from spreading

This has been underlined by the fact that high levels of natural transmission have allowed new strains to emerge — and it looks like these can go through the population and re-infect people. 

Nor do I think that anyone with expert knowledge believes we can eradicate Covid-19 in the way that we wiped out smallpox — the only virus we have managed to eradicate. But we can reduce its impact with vaccines.

I’m a great fan of vaccination, but I’m not a fan of mandatory vaccination because it generates suspicion. We need to persuade people about how great and safe these vaccines are, not threaten them with ‘no jab, no job’.

Carrots and information work better than sticks. 

Covid-19 has now killed some 2.5 million people worldwide and infected 110 million, many of whom will suffer long-term consequences, and cost the world an estimated £16 trillion.

But compared to what might have happened, we’ve got off relatively lightly. It’s estimated there are more than a million viruses in animals able to infect us, and any one may become a pandemic far worse than this. Imagine a virus that kills 5 to 10 per cent of those it infects, and that this was the death rate in children.

The next pandemic is already in the post. This month, the authorities in Guinea in West Africa declared a new Ebola outbreak; Saudi Arabia’s health ministry has reported four new cases of MERS, a coronavirus we catch from camels.

We know that the more humans invade wild ecosystems, the more we expose ourselves to deadly viruses that can jump from animal species into us. And these jumps are happening more often, driven by global consumption, health inequalities, climate change, agricultural practices and environmental destruction.

We need to improve our global surveillance systems for spotting and stopping novel viral outbreaks. If we don’t, it is a racing certainty that we will see the next pandemic within our lifetimes.

Coronavirus — A Horizon special: What We Know Now, Thursday at 9pm on BBC2.

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Immune response to insulin could identify, help treat those at risk for type 1 diabetes


Researchers from the Barbara Davis Center for Childhood Diabetes at the University of Colorado Anschutz Medical Campus have found that immune responses to insulin could help identify individuals most at risk for developing Type 1 diabetes.

The study, out recently in the Proceedings of the National Academy of Sciences, measured immune responses from individuals genetically predisposed to developing Type 1 diabetes (T1D) to naturally occurring insulin and hybrid insulin peptides. Since not all genetically predisposed individuals develop T1D, researchers sought to examine T-cell immune responses from the peripheral blood that could occur before the onset of clinical diabetes.

“We want to know why people develop T1D, and this research has helped provide a lot more information and data as to what it looks like when genetically at-risk individuals are headed towards clinical diagnosis,” says Aaron Michels, MD, the study’s lead researcher, Associate Professor of Medicine at CU Anschutz and researcher at the Barbara Davis Center. “Ideally, you want to treat a disease when it’s active, so this is a need in our field to understand when people have an immune response directed against insulin producing cells.”

Researchers collected blood samples from genetically at-risk adolescents every 6 months for two years. Inflammatory T-cell responses to hybrid insulin peptides correlated with worsening blood glucose measurements and progression to T1D development. The results indicate an important advancement in identifying the risk of T1D early as well as the potential for intervention.

“There are now therapies used in research studies that have delayed the onset of clinical type 1 diabetes,” says Michels. “Patients with these specific immune responses, may benefit from immune intervention to delay T1D onset and possibly prevent it for years.”

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Rebel Wilson Says People Treat Her Differently After 61-Pound Weight Loss

Seeing things clearly. Rebel Wilson opened up about the change she has seen in others following her dramatic weight loss after her “year of health” in 2020.

Rebel Wilson’s Weight Transformation Over the Years

“I think what’s been really interesting to me is how other people treat you,” Wilson, 40, said during an appearance on The Morning Crew With Hughesy, Ed and Erin radio show on Wednesday, January 27. “Sometimes being bigger, people didn’t necessarily look twice at you. And now that I’m in a good shape, like, people offer to carry my groceries to the car and hold doors open for you. I was like, ‘Is this what other people experienced all the time?’”

The Pitch Perfect actress, who lost more than 60 pounds last year, admitted she was surprised by how much attention people give a weight loss transformation “when there’s so much going on in the world.”

The Isn’t It Romantic star revealed that her inner beauty, however, has never changed.

Rebel Wilson Reveals Diet Secrets, What She Learned During Her ‘Year of Health’

“I like to think I looked good at all sizes and stuff and I’ve always been quite confident,” she said. “So, it wasn’t like I wasn’t confident and then now I’m, like, super confident.”

Wilson, who reached her goal weight of 165 pounds in November 2020, joked that her new outward appearance has created a bit of a selfie monster.

“You can tell that I post, like, a lot of photos of myself on Instagram. I’m like, ‘Oh yeah, loving myself,’” she said. “I know I should calm down a bit on that.”

Last month, the Australia native opened up about why she got serious about health, noting there were lots of ups and downs on her journey.

“I’ve been overweight for about 20 years and I love playing some of the comedic characters like Fat Amy from Pitch Perfect and everything. I love all that stuff but at a certain point, I knew in my heart that I was engaging in some unhealthy behaviors,” she said in a December Instagram Live video. “I needed to change those for the better and so what I’m proud of myself for is for doing that and having a lot more balance now in my life.”

Stars’ Most Dramatic Weight Loss Transformations: Photos

The comedian shared her goals for her “year of health” mission in May 2020, telling fans via Instagram that she was focused on getting to “75kgs,” which is roughly 165 pounds, and career-wise she was “trying to get one of my movies into production.”

She added: “Even if you have to crawl towards your goals, keep going x it will be worth it. Try and give a little bit of effort each day. I know some days are frustrating as hell, you feel like giving up, you get annoyed at the lack of progress … but good things are coming your way.”

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Blocking DNA repair enzyme could help treat certain cancers

Researchers at the Francis Crick Institute have found a new way to prevent some tumors from repairing their own DNA, a function that is essential for cancer cell survival. This discovery could lead to much needed new treatments for certain types of the disease.

In their study, published in Molecular Cell today, the researchers showed that blocking an enzyme called ALC1 in certain human cancer cells in the lab caused the cells to die.

It has emerged that many cancers lose specific DNA repair processes. As a consequence, these cancers become critically dependent on backup DNA repair pathways, which present an ‘Achilles heel’ that can be targeted to kill cancer cells.

Cancers that lack homologous recombination (HR), a key pathway involved in DNA repair, including some breast and ovarian cancers, can be selectively killed by PARP inhibitors. However, in about half of cases, people do not respond to these drugs and of those who do, many will eventually develop resistance.

In the search for urgently needed new drug targets to exploit DNA repair deficiencies, the team studied the effect of removing ALC1, an enzyme which plays an important role in repair of damaged DNA bases. Unexpectedly, cells lacking ALC1 were found to be exquisitely sensitive to PARP inhibitor treatment. Removing ALC1 also conferred synthetic lethality in HR deficient cancers. The researchers also found that HRD cancer patients with higher levels of ALC1 in their tumors were predicted to be less likely to survive.

Simon Boulton, senior author and group leader of the DSB Repair Metabolism Laboratory at the Crick says, “This work provides strong evidence for developing new drugs that block the ALC1 enzyme. If shown to be effective in further studies, these drugs could be used alone or in combination with existing PARP inhibitors to target HRD cancers.”

To understand why this enzyme has this particular effect, the team also analyzed the genomes of human cancer cells where ALC1 had been removed. They observed that without this enzyme, DNA gaps accumulated in the cancer cells, which are normally repaired by HR.

Graeme Hewitt, author and postdoc in the DSB Repair Metabolism Laboratory at the Crick says, “Many different types of cancer have weaknesses in their ability to repair DNA that could be targeted with new treatments.”

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How HIV became the virus we can treat

As the numbers of COVID-19 infections climb, it’s easy to forget that there are still more than 1.2 million people in the U.S. living with another virus—human immunodeficiency virus, or HIV. When it first swept across the country in the 1980s, HIV was one of the most sobering public health challenges ever faced. It brought a cruel and isolating stigma toward gay men, who died in startling numbers, and it went on to kill 33 million people across the world.

Times have changed. Now, most people don’t die from the virus. Thanks to continuing medical advances in medications, HIV can now be seen as a chronic disease. People who have it can enjoy long careers, get married, and raise families.

“The message that we used to give in the early days of HIV was, ‘Let’s try to make your remaining days as comfortable as possible.’ Now, it’s treatable. It’s not curable, but it is controllable,” says Merceditas Villanueva, MD, director of the Yale School of Medicine AIDS Program.

Many HIV providers and public health experts believe they can eventually come close to eradicating the virus by 2030 with a goal known as “95-95-95.” In this vision, 95% of people who have HIV would be diagnosed, 95% of them would be receiving treatment, and of those, 95% would have the virus suppressed (the term used when the amount of virus is so low that the patient with HIV stays healthy and has a greatly reduced chance of passing it to others).

“The ultimate goal is getting to zero—and that’s zero new diagnoses, zero new infections, zero deaths, and zero stigma,” says Lydia Aoun-Barakat, MD, medical director of the Nathan Smith Clinic, the HIV clinic at Yale New Haven Hospital (YNHH).

We asked these and other specialists in the Yale School of Medicine AIDS Program to answer questions about how HIV became a treatable disease.

What is the difference between HIV and AIDS?

HIV is a potentially deadly virus that attacks the body’s immune system, specifically the T cell lymphocytes or CD4 cells. AIDS is a collection of symptoms and illnesses that can develop when HIV goes untreated and the CD4 cell count drops below 200.

There are four stages of HIV (0, 1, 2, 3). People are diagnosed as having AIDS when their HIV is classified—or if it has ever been classified—as Stage 3, when people experience such symptoms as rapid weight loss, recurring fever or night sweats, body sores, memory loss, and (what turn out to be) fatal infections.

It first came to attention in the early 1980s when doctors started reporting unusual infections and rare malignancies in gay men. HIV is believed to have transferred from animals to humans possibly as far back as the late 1800s from a type of chimpanzee in Africa. This likely occurred when hunters looking for meat came in contact with infected blood from the animal. HIV is transmitted between humans through bodily fluids, specifically blood, semen, vaginal secretion, and breast milk.

Who is at risk for HIV today?

Anyone can be at risk for HIV, but some groups are more likely to get it than others. The first cases of HIV in the U.S. spread mostly through unprotected sexual intercourse, especially among men who have sex with men. The virus is by far still most prevalent in that group, followed by people who transmit it through heterosexual relations, and injection-drug users who share needles. It has affected Black and Hispanic Americans disproportionately, and is on the rise among transgender people.

Beyond that, people with HIV make up a diverse population, says Dr. Villanueva, who also sees a small minority infected by blood transfusions. “So, there’s a leveling feature. If you have HIV, regardless if you’re rich or poor, you’re dealing with the same disease,” she says.

While annual infections in the U.S. have decreased by more than two-thirds since the mid-1980s, recent data still show about 38,000 new infections in the U.S. each year between 2014 and 2018. The highest number of new diagnoses are in people between the ages of 20 and 35 (a population believed to most likely be unaware of their HIV status).

What treatments are helping people live longer?

A collection of antiretroviral therapies (ART) has moved HIV into the chronic disease realm and given young people who are newly infected a close-to-normal life expectancy. In fact, more than half of people living with the virus now are over 50 years old, says Michael Virata, MD, director of HIV clinical services at YNHH’s Saint Raphael Campus.

“Really, the basic goal is to treat people with highly active drugs that combat the virus, so we get them to the point where they have undetectable levels of it,” he says.

Patients may be given some combination or “cocktail” of three drugs, and doctors are moving toward two-drug combinations. “We are even moving into a realm of longer-acting agents so that people won’t have to take a pill every day,” Dr. Virata says.

Some medicines will be delivered through such methods as injections that could protect people for weeks. In the past, there was controversy over when to treat newly diagnosed patients, but current guidelines recommend starting medications quickly. “There are centers around the U.S. where, the day they diagnose you, they hand you your first doses of medication,” Dr. Virata says.

There have been breakthroughs beyond the medications as well. “For example, people with HIV with end-stage kidney disease are now being successfully transplanted,” says Dr. Villanueva. “And there are studies that show successful kidney and liver transplants from HIV-positive deceased donors.”

Have you been able to stop the spread of infection?

Yes and no, says Dr. Villanueva. “In the past five to eight years, the number of newly documented infections has decreased. But we’re looking nationally at a level of almost 38,000 new infections per year, which is a lot.”

A major approach to prevention is the use of PrEP or pre-exposure prophylaxis. This approach is based on administering drugs used to treat HIV to people who do not have HIV—but who are at a high risk for it—in an effort to prevent them from contracting the virus. Different formulations are being made available, including long-acting injectables and a vaginal ring for women, and this worldwide effort is extremely important, says Dr. Villanueva.

There have been other pockets of success. Mothers-to-be who had HIV used to transmit the virus to their infants when they gave birth, says Dr. Villanueva. But a landmark trial that Yale participated in showed that giving mothers an antiretroviral medication called azidothymidine (AZT) during the third trimester and delivery resulted in a marked decrease in the mother-to-newborn transmission rate in the U.S. “That treatment was introduced as a standard of care here in Connecticut, with only one new case of perinatal transmission since 2008,” Dr. Villanueva says.

Another pocket is the decrease in cases among injection-drug users contracting HIV when they shared needles. “Very early work here at Yale helped pioneer the use of syringe exchange programs, and it’s been a successful harm reduction approach that has been adopted not only nationally, but worldwide,” Dr. Villanueva says.

These programs provide people with access to sterile needles and syringes, as well as a safe way to dispose of used syringes. “However, the caveat is that with the opioid epidemic, we are starting to see new outbreaks of HIV among people who are using opioids through injection,” Dr. Villanueva says.

What issues do people with HIV face as they age?

Aging with HIV is a fairly new area of study. “People who are 50 and who have been living with HIV for a long time—their bodies may be, by some estimates, like that of a 60-year-old,” says Dr. Villanueva. They may develop cancer, diabetes, heart disease, and other conditions earlier than they would if they weren’t HIV-positive.

Dr. Virata says HIV is thought to cause a chronic inflammatory state in the body, which can accelerate aging. “We’re trying to understand what the process is and figure out how we can address it,” he says.

Researchers are studying whether early interventions could decrease complications for patients as they grow older. Dr. Virata points to a large global study looking at the use of statins as an intervention. “It’s a long-term study, but we’re anxiously waiting to see what the results of that research project will show,” he says. Contributing to the problem, he says, is that some of the medications used to treat HIV can be toxic in the body.

More implementation science, research, and intervention strategies are needed, Dr. Barakat says. “We’re still learning about and determining the best strategies to enhance opportunities as far as testing and prevention.”

How has testing, an important COVID-19 strategy, helped with HIV?

HIV testing is critical because—as with COVID-19—many people who have the virus don’t know it. An estimated 14% of people with HIV in the U.S. (or one in seven) are not aware they have it. Symptoms aren’t always a tip-off, since about a third of newly infected people don’t develop symptoms (two-thirds report flu-like symptoms within two to four weeks of infection) but are still able to transmit it to others.

In 2006, the Centers for Disease Control and Prevention (CDC) recommended offering HIV tests to anyone between the ages of 18 and 65 coming into the health care system for any reason, regardless of their background or risk factors. Dr. Barakat would go a step further. “Every single person should be tested for HIV—annually, if they are at higher risk,” she says. High-risk groups would include those who use drugs and share needles or engage in unprotected sex.

Testing is important because once a person is diagnosed, he or she is more likely to be treated, and therefore less likely to spread the disease to others, says Dr. Virata.

Can our experience with HIV help with COVID-19?

HIV specialists say there are many similarities between HIV and COVID-19. For both diseases, “the first step is testing, the second step is prevention,” says Dr. Barakat. “If you know who is infected, you can take care of them, and they will be less likely to infect others. And for those who are uninfected, you can provide them with prevention measures.”

For both conditions, getting people to take precautions is a difficult challenge. “For a lot of infectious diseases, the most important prevention intervention is the social behavior part of it,” says Dr. Barakat. “You see this with COVID-19 and you see it with influenza or Ebola. People’s beliefs and attitudes are very important when you are dealing with an epidemic. There needs to be a lot of public education, as well as access to information, testing, and treatment,” she says.

Both conditions call for a vaccine. While it may be years away, the doctors hope there will be an HIV vaccine in their lifetimes; more progress has been made on a COVID-19 vaccine.

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First drug approved to treat rare metabolic disorder

(HealthDay)—The U.S. Food and Drug Administration approved the first treatment for the rare genetic disorder primary hyperoxaluria type 1 (PH1), the agency announced Monday.

Oxlumo (lumasiran) is approved to treat PH1, the most common and most severe type of primary hyperoxalurias, which can lead to progressive kidney damage and eventually damage to other organs. One to three individuals per million in North America and Europe are believed to be affected by PH1.

The approval of Oxlumo was based on data from two studies. In the first study, a randomized, placebo-controlled trial, 26 patients aged 6 years and older received a monthly injection of Oxlumo followed by a maintenance dose every three months, while 13 patients received placebo injections. Patients who received Oxlumo had an average 68 percent reduction of oxalate in the urine compared with a 12 percent reduction for patients who received placebo. After six months, 52 percent of patients treated with Oxlumo versus none who received placebo reached a normal 24-hour urinary oxalate level. The second study was an open-label study of 16 patients all younger than 6 years who received Oxlumo. Data showed an average 71 percent decrease in oxalate in the urine after six months.

The most commonly reported side effects of Oxlumo include injection site reaction and abdominal pain.

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DR MICHAEL MOSLEY: Why won't the NHS tell you how to treat diabetes?

DR MICHAEL MOSLEY: Why won’t the NHS tell you the secret to treating diabetes? (Clue: It costs nothing)

Eight years ago I managed to beat type 2 diabetes by going on my 5:2 diet (cutting my calories two days a week) and losing weight — 9kg to be precise. 

Since then I’ve become something of a broken record on the importance of shedding body fat to improve your blood sugar levels.

So I was delighted last week by the news from the Norfolk Diabetes Prevention Study — the largest of its kind in the world — which showed that even modest weight loss can have a big impact.

A recent review by Danish researchers found more than 70 per cent of people with type 2 diabetes who had lost significant amounts of weight were still medication-free more than five years later [File photo]

The Norfolk study recruited more than 1,000 people with pre-diabetes (meaning they had raised blood sugar levels). They were asked to lose weight, then were monitored for more than eight years. Those who managed to lose 2kg to 3kg, and keep it off, almost halved their risk of developing full-blown type 2.

This adds to extensive research carried out by British scientists showing that, as well as pre-diabetes, type 2 diabetes can be put into remission by going on a rapid weight-loss diet. And, as we’ve known for 20 years, weight-loss surgery can also reverse type 2.

In fact, a recent review by Danish researchers found more than 70 per cent of people with type 2 diabetes who had lost significant amounts of weight were still medication-free more than five years later.

Despite all this, the NHS Choices website still tells you type 2 diabetes is a ‘progressive’ disease that ‘usually gets worse over time’, with most people needing ever increasing levels of medication. What a depressing — and I would argue inaccurate — message.

So why aren’t they being a bit more encouraging? The situation with type 2 diabetes reminds me of a tussle I had with the medical establishment more than 25 years ago. 

In 1993 I was looking around for a subject to make a science documentary, when I came across the work of two Australians, Dr Barry Marshall and Dr Robin Warren, who had a striking new theory about stomach ulcers.

I was delighted last week by the news from the Norfolk Diabetes Prevention Study — the largest of its kind in the world — which showed that even modest weight loss can have a big impact [File photo]

At the time, stomach or duodenal ulcers (affecting the first part of the small intestine) were incredibly common but, like type 2, were seen as something of a mystery.

Gut ulcers can be excruciatingly painful and lead to internal bleeding. Doctors knew they were caused by excess acid and they could be managed by drugs such as ranitidine, which stopped the stomach from producing acid. These drugs, known as proton pump inhibitors, were expensive but there was a lot of incentive to use them because if you didn’t, or if the drugs stopped working, there was a high chance you’d need some of your stomach and intestines removed.

Robin and Barry, however, were convinced they had a cheap and effective cure. Their research showed that most patients with ulcers were infected with a bacterium, which the two doctors called Helicobacter pylori.

The patients’ stomachs were producing more acid to get rid of the bacterium, but this failed because Helicobacter is resistant to acid attack. But it is vulnerable to the right antibiotics.

To prove the point, Barry deliberately infected himself with Helicobacter (he swallowed a flask of it) and soon developed gastritis — massive inflammation — which he cured with a short course of antibiotics. This was in 1984.

Nine years later, when I began filming with Robin and Barry, there was still widespread resistance to their claims, despite extensive proof they were right.

When I asked Barry how long he thought it would take to persuade his colleagues to take their claims seriously, he laconically replied, ‘Well it’s been ten years and ten per cent of doctors are treating ulcers this way. Perhaps in 100 years they will all be doing it.’

In fact, within ten years almost all doctors were doing it. Not least because Barry and Robin won the Nobel Prize for Medicine in 2004 for their work.

But back in 1994, when my documentary, Ulcer Wars, detailing their work, came out, the medical reaction was either indifference or hostility. A review in The British Medical Journal by a leading gastroenterologist described the film as ‘one sided and tendentious’.

However, patients with duodenal ulcers who’d watched the programme soon began demanding antibiotic treatment.

Many later wrote to me and as one man put it: ‘I saw your programme a week before I was due to have surgery, and it was only because my doctor was prepared to listen that I was cured by antibiotics rather than having a chunk of my guts removed.’

Why did it take so long for doctors to adopt this approach, despite overwhelming evidence that eradicating Helicobacter could change patients’ lives? This was a question that researchers from Harvard asked in 2019 — concluding that it was mainly because doctors get much of their information from pharmaceutical companies, and these companies had no incentive to promote a cheap alternative to their acid-reducing drugs (which, of course, you took for life).

The parallels with type 2 diabetes are clear. As the millions of those affected in the UK will know, type 2 is usually treated with medication. 

While this will reduce the long-term damage caused by high blood sugar levels, it doesn’t deal with the underlying disease — and like all medication, the drugs can have significant side-effects, particularly when you move on to injecting insulin.

So how long before there’s widespread acceptance that most cases of type 2 diabetes can be put into remission by a rapid weight-loss diet? 

It is beginning to happen, but I wouldn’t guarantee that NHS Choices will be telling you the good news any time soon.

Like us, worms need to sleep. And the way their bodies prepare for sleep is also surprisingly similar to humans — one of the key triggers for a bit of shut eye is the release of melatonin, also known as the ‘hormone of darkness’.

Melatonin is produced in your brain and levels rise when it gets dark (synthetic melatonin is a popular sleep aid and is used to treat jet lag — I find it very effective).Now researchers at the University of Connecticut have discovered how melatonin actually works — in worms at least.

It slows the release of neurotransmitters, substances that allow messages to travel between nerve cells. So melatonin effectively tells your brain cells to stop chatting to each other — the chemical equivalent of a giant ‘shhh’!

Covid-19 vaccines are like buses; you wait for one, then two come along, almost together, with other contenders coming close behind.

This week we learnt that the vaccine made by Moderna may be even more effective than Pfizer’s. That both are more than 90 per cent effective is fantastic news and a real poke in the eye for the sceptics who claimed we might never get a vaccine against Covid-19, let alone several.

These findings also suggest that our immune system is doing what evolution designed it to do: mount a strong response to the virus.

There was a fear that Covid-19 might mutate into a more resistant form — or that our immune response might weaken. 

Yet recent research suggests that while antibody levels tend to fall over time, your immune system retains a ‘memory’ of the virus. So if you encounter it again, your body is ready to begin churning out antibodies and T-killer cells.

Which makes me wonder why Boris, who’s had Covid, is self-isolating. He’s unlikely to be ‘bursting with antibodies’ as he claims, but he’s also very unlikely to get it again, or to be infectious, so I can’t see how he’s a threat to others. 

Our immune system has been severely tested by Covid, but as the new vaccines show, it just needs a bit of help to get back on top.

Covid-19 vaccines are like buses; you wait for one, then two come along, almost together, with other contenders coming close behind [File photo]

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Cannabis to treat gynecological conditions

A significant number of women would consider using cannabis to treat gynecological conditions, primarily gynecological pain. Women with a history of cannabis use are reported in a study in Journal of Women’s Health.

Women who self-medicate with cannabis do so to relieve chronic pelvic pain, menstrual cramps, and pain associated with gynecological cancer or medical procedures such as abortion.

“A larger proportion of women who reported ever using cannabis were willing to use cannabis to treat conditions commonly seen in gynecological practices compared to never-users (91.6% vs. 64.6%),” states Leo Han, MD, MPH, and coauthors, from Oregon Health & Science University. This difference was statistically significant.

“Coinciding with the increased perception of cannabis safety is the increased national recognition of the dangers of opioid pain medications,” says the authors.

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Study reinforces drug’s potential to treat hypertrophic cardiomyopathy

Research at Washington State University sheds new light on one molecule that may be used to treat a heart condition that can lead to stroke, heart attack and other forms of heart disease.

That molecule is mavacamten. Scientists at WSU’s Integrative Physiology and Neuroscience department discovered it suppresses excessive force generated by hyper-contractile muscle cells in the human heart.

The research, published in the British Journal of Pharmacology, is especially significant for those with hypertrophic cardiomyopathy, a genetic condition where the left ventricle wall of the heart is enlarged. If left untreated, hypertrophic cardiomyopathy can lead to cardiac fibrosis, stroke, heart attack, heart failure, other forms of heart disease and a condition known as sudden arrhythmic death syndrome.

“Too much contraction leads to thicker, stiffer hearts, where the heart contracts so much it is unable to properly fill with blood as the heart relaxes,” said Peter Awinda, first author on the paper and scientific manager in Bertrand Tanner’s laboratory at WSU. “This ends up pushing less blood out of the heart with each heartbeat and, in turn, less blood pumped throughout the body like it is supposed to be.”

Hypertrophic cardiomyopathy affects men and women equally. About 1 out of every 500 people have the disease.While there are some genetic markers to detect it, most people only discover their condition after a cardiac event that often results in a hospital visit.

The research

The project is a collaboration between the Tanner Laboratory in Pullman and Ken Campbell’s laboratory at University of Kentucky. Campbell manages a human cardiac biobank, where he ships tissue samples frozen in liquid nitrogen to Tanner, who is the principal investigator for the research.

After arriving in Pullman, the cardiac tissue was thawed, ‘skinned’ to remove the cell membrane, and trimmed to the right dimensions for an experiment.

Three micrograms of the drug, mavacamten, were then applied to some of the prepared tissue samples; other samples did not receive the drug and were labeled as controls.

To activate muscle contraction Awinda applied calcium to the tissue.

“As we increase calcium concentration it encourages contraction and the muscle goes from relaxed to contracted, and so we were testing the drug against these different levels of force,” Awinda said.

He found the drug reduces the maximal force of contraction by nearly 20 to 30% compared to the controls.

“The drug is successful because it is an inhibitor of myosin, which is one of the proteins required for the muscle contraction process,” Awinda said. “The research shows this could be a good candidate to treat hypertrophic cardiomyopathy.”

The collaborative study was made possible by organ donors and their families. The work was paid for by a $300,000 grant from the American Heart Association to Tanner and Campbell.

These initial studies helped Tanner and Campbell add an additional $2.8 million grant from the National Institutes of Health to support additional work in this area over the next 4 years.

Next steps

One of the research team’s next goals is to see how mice with a human mutation for hypertrophic cardiomyopathy respond to the drug.

Awinda said researching mice expressing the human gene is significant because it may provide a connection to what is seen in humans.

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