Tag: Drug

Categories
Life Style

Major AlphaFold upgrade offers boost for drug discovery

[ad_1]

A close up view of detail from a computer render of a AziU3/U2 protein diagram.

An AlphaFold3 model of a bacterial enzyme bound to a chemical.Credit: Isomorphic Labs

Since the powerhouse artificial intelligence (AI) tool AlphaFold2 was released in 2021, scientists have used the protein-structure-prediction model to map one of our cells’ biggest machines, discover drugs and chart the universe of every known protein.

Despite such successes, John Jumper — who leads AlphaFold’s development at Google DeepMind in London — is regularly asked whether the tool can do more. Requests include the ability to predict the shape of proteins that contain function-altering modifications, or their structure alongside those of DNA, RNA and other cellular players that are crucial to a protein’s duties. “I would say ‘no, you can’t put that into AlphaFold’,” Jumper says. “I would rather solve their problems.”

The latest version of AlphaFold, described on 8 May in Nature1, aims to do just that — by giving scientists the ability to predict the structures of proteins during interactions with other molecules. But whereas DeepMind made the 2021 version of the tool freely available to researchers without restriction, AlphaFold3 is limited to non-commercial use through a DeepMind website.

Frank Uhlmann, a biochemist at the Francis Crick Institute in London who gained early access to AlphaFold3, has been impressed with its capabilities. “This is just revolutionary,” he says. “It’s going to democratize structural-biology research.”

Another revolution

“Revolutionary” is how many scientists have described the impact of AlphaFold2 on biology since it was unleashed2 (the first version3, released in 2020, was good, but not game-changing, Jumper has said). The AI predicts a protein’s structures from its amino-acid sequence, often with startling accuracy that is on par with that of experimental methods.

A freely available AlphaFold database holds the predicted structure of nearly every known protein. The availability of the AlphaFold2 code has also allowed other researchers to easily build on it: an early hack enabled the prediction of interactions between multiple proteins, a capability included in an update to AlphaFold2.

Jumper’s ennui over explaining AlphaFold’s inability to predict other aspects of a protein’s ecosystem stems from their importance: protein modifications, such as the addition of a phosphate molecule, can allow cells to respond to external cues, an infection, for instance, and set off a chain of events in response. Interactions with DNA, RNA and other chemicals are essential to many proteins’ duties.

Real-world examples of these interactions are readily available in the Protein Data Bank (PDB), a repository of experimentally determined structures that is the foundation of AlphaFold’s capabilities. An ideal tool would be able to predict structures of a protein alongside its accessories, says Jumper. “We want to solve the whole PDB.”

Major upgrade

To create AlphaFold3, Jumper, DeepMind chief executive Demis Hassabis and their colleagues made large changes to its predecessor: the latest version depends less on information about proteins related to a target sequence, for instance. AlphaFold3 also uses a type of machine-learning network — called a diffusion model — that is used by image-generating AIs such as Midjourney. “It’s a pretty substantial change,” says Jumper.

AlphaFold3, the researchers found, substantially outperforms existing software tools at predicting the structure of proteins and their partners. For instance, scientists — especially those interested in finding new drugs — have conventionally used ‘docking’ software to physically model how well chemicals bind to proteins (usually with help from the proteins’ experimentally determined structures). AlphaFold3 proved superior to two docking programs, as well as to another AI-based tool called RoseTTAFold All-Atom4.

Uhlmann’s team has used AlphaFold3 to predict the structure of DNA-interacting proteins involved in copying the genome, a step that is essential to cell division. Experiments in which proteins are mutated to alter such interactions suggest that the predictions were usually spot on, Uhlmann says. “It’s an amazing discovery tool,” he adds.

“The structure-prediction performance of AlphaFold3 is very impressive,” says David Baker, a computational biophysicist at the University of Washington in Seattle. It’s better than RoseTTAFold All-Atom, which his team developed4, he adds.

Restricted access

Unlike RoseTTAFold and AlphaFold2, scientists will not be able to run their own version of AlphaFold3, nor will the code underlying AlphaFold3 or other information obtained after training the model be made public. Instead, researchers will have access to an ‘AlphaFold3 server’, on which they can input their protein sequence of choice, alongside a selection of accessory molecules.

Uhlmann likes what he has so far seen of the server, which he says is simpler and quicker than the version of AlphaFold2 that he has access to at his institute. “You upload it and 10 minutes later, you’ve got the structures,” he says. For most scientists, “the server is really going to smash it. Everybody can do it.”

Access to the AlphaFold3 server, however, is limited. Scientists are currently restricted to 10 predictions a day, and it is not possible to obtain structures of proteins bound to possible drugs.

Isomorphic Labs, a DeepMind spin-off company in London, is using AlphaFold3 to develop drugs, both through its own pipeline and with other pharmaceutical companies. “We have to strike a balance between making sure that this is accessible and has the impact in the scientific community as well as not compromising Isomorphic’s ability to pursue commercial drug discovery,” says Pushmeet Kohli, DeepMind’s head of AI science and a study co-author.

Because of the restriction on modelling protein interactions with possible drugs, “I can’t see it having the impact AlphaFold2 had”, says Brian Shoichet, a pharmaceutical chemist at the University of California, San Francisco, who has been using AlphaFold structures to hunt for therapeutic candidates.

Sergey Ovchinnikov, an evolutionary biologist at the Massachusetts Institute of Technology in Cambridge, had hoped to develop a web version of AlphaFold3, as he and his colleagues have done for AlphaFold2 shortly after its code was released. But based on the ample information provided in the latest Nature paper, it shouldn’t take long for other teams to create their own versions, he says. “I would expect open-source solutions before the end of the year.”

[ad_2]

Source Article Link

Categories
Life Style

Diabetes drug shows promise against Parkinson’s

[ad_1]

Hello Nature readers, would you like to get this Briefing in your inbox free every day? Sign up here.

Viewers along the eclipse’s path in North America will watch the Moon cross the Sun’s face and block the solar disk, offering the chance to see its outer atmosphere by eye.Credit: Alan Dyer/VW Pics/UIG via Getty

On 8 April, researchers will get an unprecedented view of the Sun’s outer wispy atmosphere: the corona. The solar eclipse visible in parts of North America will coincide with a solar maximum — a period of extreme activity that occurs every 11 years. One research team will chase the eclipse from a jet, adding 90 more seconds of observation time to the maximum of 4 minutes and 30 seconds seen by observers on the ground. One question they’re hoping to answer: why the corona is so much hotter than the solar surface. That, says solar physicist James Klimchuk, is like walking away from a campfire — but finding that instead of cooling down, you get warmer.

Nature | 6 min read

A diabetes drug called lixisenatide has shown promise in slowing the progression of Parkinson’s disease. Lixisenatide is in the family of GLP-1 receptor agonists, such as Ozempic, that have made headlines as weight-loss drugs. In the latest clinical trial, lixisenatide was given to people with mild to moderate Parkinson’s who were already receiving a standard treatment for the condition. After a year they saw no worsening of their symptoms, unlike a control group whose condition did worsen. Further work is needed to reduce the drug’s side effects, such as nausea and vomiting, and to determine whether its benefits last. “We’re all cautious. There’s a long history of trying different things in Parkinson’s that ultimately didn’t work,” says neurologist David Standaert.

Nature | 4 min read

Reference: The New England Journal of Medicine paper

The Bill & Melinda Gates Foundation, one of the world’s top biomedical research funders, will from next year require grant holders to make their research publicly available as preprints, which are not peer reviewed. It will also no longer pay article-processing charges (APCs) to publishers in order to secure open access, in which the peer-reviewed version of the paper is free to read. The change follows criticism that APCs create inequities because of the costs they push onto researchers and funders. “We’ve become convinced that this money could be better spent elsewhere,” said a Gates representative.

Nature | 7 min read

Features & opinion

This week marks 30 years since the start of the 1994 genocide in Rwanda, in which members of the Hutu ethnic group killed an estimated 800,000 people from Tutsi communities. The event is now one of the most researched of its kind. These studies are difficult, not least because because the genocide almost wiped out Rwanda’s academic community. But efforts, especially by local researchers, are helping to inform responses to other violent crises and longer-term approaches to healing. Sociologist Assumpta Mugiraneza is leading challenging work that gathers testimonies from the genocide — and of the rich lives people had before the atrocity. To think about genocide, she says, “we must dare to seek humanity where humanity has been denied”.

Nature | 17 min read

Two future academics — a rat and a raven — ponder the fate of past primates in the latest short story for Nature’s Futures series.

Nature | 6 min read

Andrew Robinson’s pick of the top five science books to read this week includes an account of women working in nature and a thoughtful history of how our unequal society deals with epidemics.

Nature | 4 min read

When Brazilian biologist Fernanda Staniscuaski returned from parental leave, her grant applications started to be rejected because she “was not producing as much as my peers”. “Maybe I was never meant to be in science,” she recalls thinking. As the founder of the Parent in Science movement, she is now lobbying for greater acceptance of career breaks. As a first step, the Brazilian Ministry of Education has created a working group to develop a national policy for mothers in academia. “That was huge,” Staniscuaski says.

Nature Careers Working Scientist podcast | 20 min listen

Quote of the day

When the remains of the Australopithecus afarensis nicknamed ‘Lucy’ were discovered in 1974, we never could have predicted how rare such finds would be, says paleoanthropologist Bernard Wood. Nevertheless, the accumulated evidence of even older hominins has challenged Lucy’s status as ‘mother of us all’. (Science | 14 min read)

In our penguin-puzzle this week, Leif Penguinson is exploring a rock formation on the Barker Dam Trail in Joshua Tree National Park, California. Can you find the penguin?

The answer will be in Monday’s e-mail, all thanks to Briefing photo editor and penguin wrangler Tom Houghton.

This newsletter is always evolving — tell us what you think! Please send your feedback to [email protected].

Flora Graham, senior editor, Nature Briefing

With contributions by Katrina Krämer, Sarah Tomlin and Sara Phillips

Want more? Sign up to our other free Nature Briefing newsletters:

• Nature Briefing: Anthropocene — climate change, biodiversity, sustainability and geoengineering

• Nature Briefing: AI & Robotics — 100% written by humans, of course

• Nature Briefing: Cancer — a weekly newsletter written with cancer researchers in mind

• Nature Briefing: Translational Research covers biotechnology, drug discovery and pharma

[ad_2]

Source Article Link

Categories
Life Style

Diabetes drug slows development of Parkinson’s disease

[ad_1]

A diabetes drug related to the latest generation of obesity drugs can slow the development of the symptoms of Parkinson’s disease, a clinical trial suggests1. Participants who took the drug, called lixisenatide, for 12 months showed no worsening of their symptoms — a gain in a condition marked by progressive loss of motor control.

Further work is needed to control side effects and determine the best dose, but researchers say that the trial marks another promising step in the decades-long effort to tackle the common and debilitating disorder.

“This is the first large-scale, multicentre clinical trial to provide the signs of efficacy that have been sought for so many years,” says Olivier Rascol, a Parkinson’s researcher at Toulouse University Hospital in France, who led the study.

The diabetes connection

Lixisenatide is a glucagon-like peptide-1 (GLP-1) receptor agonist, making it part of a large family of similar compounds used to treat diabetes and, more recently, obesity. (The weight-loss drug semaglutide, sold under the brand name Wegovy, is a GLP-1 compound.)

Many studies have shown a link between diabetes and Parkinson’s2. People with diabetes are around 40% more likely to develop Parkinson’s. And people who have both Parkinson’s and diabetes often see more rapid progression of symptoms than do those who have only Parkinson’s.

Animal studies3 have suggested that some GLP-1 drugs, which influence levels of insulin and glucose, can slow the symptoms of Parkinson’s. Smaller trials, published in 20134 and 20175, suggested that the GLP-1 molecule exenatide, another diabetes drug, could do the same in people.

Progression halted

In the latest, larger study, the French researchers investigated lixisenatide in 156 people with mild to moderate Parkinson’s symptoms, all of whom were already taking the standard Parkinson’s drug levodopa or other drugs. Half got the GLP-1 drug for a year and the others received a placebo.

After 12 months, those in the control group showed a worsening of their symptoms. Specifically, their score had increased by three points on a scale used to assess the severity of Parkinson’s that measures how well people can perform tasks including speaking, eating and walking.

Those taking the drug had no change in their scores on this scale. But the treatment did induce side effects. Nausea occurred in nearly half, and vomiting in 13%, of people on the medication. The results are published in The New England Journal of Medicine.

Not a miracle drug

David Standaert, a neurologist at the University of Alabama at Birmingham, who was not involved in the trial, says it’s important to know whether the effect will last beyond a year.

“We’re all cautious. There’s a long history of trying different things in Parkinson’s that ultimately didn’t work,” he says. A difference of three points in the rating score is a small change — one that many people with Parkinson’s would struggle to notice, he says. “What happens at 5 years? Is it 15 points then, or is it still 3? If it’s still 3, then this is not worth it.”

Lixisenatide as a diabetes treatment was pulled from the US market last year by its Paris-based manufacturer Sanofi for commercial reasons. But Standaert says that this would not have affected development of a possible treatment for Parkinson’s, because other GLP-1 drugs are available.

“I view this as a study of the class. I don’t know if this particular one is the right answer,” he says. Newer GLP-1 drugs (lixisenatide was developed in the 2000s) could offer fewer and milder side effects or work at lower doses, he adds.

Another question that needs further consideration is just how some GLP-1 drugs might protect against Parkinson’s. The compounds are known to reduce inflammation, which has led some researchers to suggest that they prevent the steady loss of dopamine-producing neurons that drives the condition. That would offer a significant benefit over existing treatments such as levodopa, which mask the symptoms but don’t address the underlying cause. But this trial and others haven’t assessed neuron loss.

Researchers are now waiting for the results of a large clinical trial examining the effects of a two-year course of exenatide in people with Parkinson’s disease. Those data will be available in the second half of this year, according to Tom Foltynie, a neurologist at University College London, in comments provided to the UK Science Media Centre.

[ad_2]

Source Article Link

Categories
Life Style

mRNA drug offers hope for treating a devastating childhood disease

[ad_1]

A drug that uses messenger RNA technology has shown early success in addressing the core deficiency behind a rare genetic disorder. The results have ignited hope that the technology — which first gained attention through its breakthrough use in COVID-19 vaccines — could realize its long-awaited promise of generating therapeutic proteins directly in the body.

This clinical advance, reported today in Nature1, provides a boost to current mRNA applications, which remain limited to vaccines.

“This is a first step in the right direction,” says Katalin Karikó, a Nobel prizewinning pioneer of mRNA technologies who is affiliated with the University of Szeged in Hungary and the University of Pennsylvania in Philadelphia.

Yet challenges remain — especially the fleeting nature of mRNA and the side effects it causes, which complicate the path towards widespread adoption.

Metabolic makeover

Designed by Moderna in Cambridge, Massachusetts, the current therapy uses mRNA technology to restore metabolic function in people with propionic acidaemia.

This rare genetic disorder, which affects about one in 100,000 individuals worldwide, arises from mutations in either of two genes that together encode an enzyme necessary for the efficient breakdown of certain protein components. Without this enzyme, cells can’t process some nutrients properly.

That leads to the accumulation of toxic chemicals in the blood and tissues, and damages vital organs, including the heart and the brain. Symptoms, such as vomiting, usually start within the first few days after birth.

People can manage the condition with measures such as special diets. But there are currently no treatments that tackle the underlying cause directly.

Moderna’s drug, known as mRNA-3927, aims to address that gap. It contains two mRNA sequences that each craft parts of the otherwise faulty enzyme. These mRNAs are encased in a tiny fat bubble — called a lipid nanoparticle — similar to the carrier used in the company’s COVID-19 vaccine.

The therapeutic mRNA drug is administered slowly through hours-long infusions every two or three weeks. It is also given in doses hundreds of times greater than those of COVID-19 vaccines. Once the therapy enters the bloodstream, the lipid nanoparticles help to direct the mRNA to cells in the liver, where the functional enzyme is made.

Trade-offs and benefits

Initial results from a small trial of mRNA-3927 indicate that the restoration of enzymatic activity is beneficial. Eight of the 16 participants had experienced life-threatening episodes connected to their impaired metabolism in the year before starting treatment. For those eight, the likelihood of experiencing another such event decreased by an average of 70–80% while taking the therapy.

This outcome, based on a small number of people, did not reach the threshold of statistical significance. Nonetheless, “it’s a very encouraging step”, says Jerry Vockley, a medical geneticist at the University of Pittsburgh Medical Center in Pennsylvania who helped to design the trial but who was not involved in its execution.

According to Kyle Holen, head of therapeutics development at Moderna, the company is now recruiting more trial participants as it advances mRNA-3927 towards the goal of marketing approval.

Moderna is also analysing other outcome measures related to quality-of-life metrics — indicators that, anecdotally at least, seem to be improving for some recipients of the treatment.

Nassrine Fawaz in Livonia, Michigan, has witnessed a transformation in her 4-year-old daughter, who has received mRNA-3927 for the past 2.5 years. After each infusion, “she’s focused, she’s energetic, she’s up and ready for the day — all of those great things”.

Room for improvement

Developers of mRNA therapeutics had long worried that repeated administration might trigger immune responses against the treatment. However, with individuals having now received regular infusions of mRNA for months or even years without issue, this concern has been alleviated.

“That’s pretty big,” says Alex Wesselhoeft, director of RNA therapeutics at Mass General Brigham’s Gene and Cell Therapy Institute in Cambridge, Massachusetts.

But there are trade-offs: most people reported side effects in response to the treatment. These ranged from infections to severe swelling of the pancreas. However, as study investigator Andreas Schulze, a metabolic-disease specialist at the Hospital for Sick Children in Toronto, Canada, points out, many of the reactions are more likely to be “related to the underlying disease” than to the treatment.

Still, with a side-effect profile close to what Wesselhoeft describes as the “upper limit of tolerability”, and only modest clinical gains, he and others think that further refinements are needed before mRNA technologies can provide a fully corrective and long-term solution to genetic diseases.

“I’m just doubtful this is going to be a long-term therapy,” says Romesh Subramanian, a biotechnology consultant in Framingham, Massachusetts, who, in a previous job, worked in collaboration with Moderna scientists to develop mRNA therapies for rare diseases. “I think it needs to be much less frequent dosing with better [nanoparticles] or more potent mRNA.”

Meanwhile, many families affected by propionic acidaemia are maintaining a wait-and-see attitude. “The verdict is still out,” says Jill Chertow, founder and president of the Propionic Acidemia Foundation, a non-profit organization based in Deerfield, Illinois.

“We can only be hopeful since, right now, that’s all that we have.”

[ad_2]

Source Article Link

Categories
Life Style

First US drug approved for a liver disease surging around the world

[ad_1]

Coloured TEM of a section through liver tissue in a case of hepatic steatosis (fatty liver disease).

Liver tissue from a person with extra fat in the organ.Credit: IKELOS GmbH/Dr. Christopher B. Jackson/Science Photo Library

For the first time, the US Food and Drug Administration has approved a drug to treat an obesity-linked liver disease that is on the rise around the globe and is becoming a leading driver of liver failure and transplants.

The drug, called resmetirom, has been shown to reduce scar tissue in the liver and other hallmarks of a disease called metabolic dysfunction-associated steatohepatitis (MASH). MASH is often associated with the metabolic turmoil that can accompany obesity and diabetes, and in severe cases can lead to liver failure or cancer.

The disease affects an estimated 5% of the world’s adults. “It’s a huge population,” says Na Li, a hepatologist at Ohio State University Wexner Medical Center in Columbus. “And I think we have made a big step forward to improve their care.”

Worth the wait?

That step has been a long time coming: despite the clear need, pharmaceutical companies have struggled to develop a successful treatment for MASH. Last year, Intercept Pharmaceuticals in Morristown, New Jersey, abandoned a highly anticipated drug called obeticholic acid, amid concerns from the US Food and Drug Administration (FDA) that its modest effectiveness was not enough to outweigh safety risks.

“Many trials over the years have failed, even those that initially looked promising,” says Li. “That’s the tragedy we’ve had.”

MASH is caused by an accumulation of toxic, fatty molecules in the liver. Over time, this leads to inflammation and tissue damage. As the liver begins to accumulate scar tissue, a process called fibrosis, its ability to function declines. (MASH was called nonalcoholic steatohepatitis, or NASH, until professional societies adopted new nomenclature last year.)

Resmetirom boosts the liver’s ability to respond to thyroid hormone, which in turn stimulates the organ’s metabolism of fatty acids. In a year-long, multinational clinical trial in 966 people with MASH, researchers found that the drug reduced inflammation and fat build-up in 30% of participants who received the highest dose of resmetirom, compared with about 10% of those who took a placebo1. Fibrosis improved in about 26% of the highest-dose group, compared with 14% of the placebo group, making resmetirom the first candidate MASH drug to reduce fibrosis. It will be marketed as Rezdiffra and will be available to people with moderate to severe liver scarring.

Long-term benefits in doubt

The drug’s effectiveness, coupled with relatively mild side effects, was exciting and suggested that there could finally be a way to treat MASH, says Maya Balakrishnan, a gastroenterologist at Baylor College of Medicine in Houston, Texas. But the FDA granted resmetirom accelerated approval: for the drug to stay on the market, its developer, Madrigal Pharmaceuticals in Conshohocken, Pennsylvania, will eventually need to provide long-term evidence that it produces meaningful benefits.

“Only time will tell,” says Balakrishnan. “In the end, what matters is: does this drug improve survival?”

In the meantime, researchers are eagerly anticipating results from a study of semaglutide, a popular weight-loss drug, against MASH. Weight loss has been associated with a reduction in MASH severity, but an early clinical trial of semaglutide in participants with MASH yielded mixed results: some hallmarks of the disease improved, but liver fibrosis did not2. Still, researchers hope that semaglutide could help, and that the larger ongoing trial will provide clearer results, says Li.

In the meantime, resmetirom could be the best recourse for people with MASH. But physicians must be clear about the limited data on the drug when they discuss resmetirom with their patients, says Balakrishnan.

Access will be another issue, she says. Many of the people most in need of treatment are members of disadvantaged communities in which obesity and diabetes are prevalent. They often have limited access to health care, and it’s not yet known how much resmetirom will cost. “Who are the patients who are going to be able to access the medication?” says Balakrishnan. “It’s definitely a big concern.”

Potential blockbuster

Access in other countries will have to wait. Madrigal Pharmaceuticals’ clinical trials of resmetirom focused on the United States, says Claudia Oliveira, a pathologist at the University of São Paulo in Brazil. “We did not get the opportunity to see this drug in patients in Latin America,” she says. “But we all have expectations about the drug, because the results of the trial were very, very interesting.”

“Madrigal is a small company and chose to focus on a more limited geographic footprint for our trials,” a spokesperson for the company told Nature.

That decision likely helped speed the company’s first approval, says Norberto Chavez Tapia, a hepatologist at Médica Sur in Mexico City. Soon, he predicts, resmetirom will be investigated in clinical trials around the world.

After that, depending on the drug’s price and effects on transplants and survival, resmetirom could be welcomed in many health-care systems, says Tapia: “It’s a very attractive drug for us, worldwide.”

[ad_2]

Source Article Link

Categories
Life Style

Blockbuster obesity drug leads to better health in people with HIV

[ad_1]

Light micrograph of white adipose tissue, or fat, stained with haematoxylin and eosin.

Long-term use of antiretroviral drugs can cause abnormal fat accumulation in people with HIV.Credit: Jose Calvo/SPL

People with HIV are the latest group to benefit from the new generation of anti-obesity drugs. If early data about the treatments’ effects are confirmed, the drugs could become key to controlling the metabolic problems often caused by anti-HIV medications.

Studies presented last week at the Conference on Retroviruses and Opportunistic Infections in Denver, Colorado, suggest that the anti-obesity drug semaglutide not only helps people with HIV to lose weight but also reduces certain conditions associated with fat accumulation that are especially common in people infected with the virus.

The number of people who are overweight or have obesity is increasing among those with HIV, driving interest among both affected individuals and medical providers in medications such as semaglutide, says Daniel Lee, a physician at the University of California San Diego Medical Center. At his clinic, which treats people with metabolic complications of HIV therapies, around 20% of patients already receive semaglutide or other drugs of the same class.

“For the most part, we’ve had very good experiences with these medications,” Lee says. But, so far, few studies have looked at the effect of the blockbuster anti-obesity drugs on people with HIV.

Unwanted side effects

Although the increasing incidence of obesity in people with HIV is similar to the trend in the general population, certain antiretroviral medications used to suppress HIV could contribute further to weight gain and weight-related conditions in these individuals1,2.

Semaglutide, marketed as Wegovy for obesity and Ozempic for diabetes, mimics a hormone called glucagon-like peptide 1, which helps to lower blood sugar levels and control appetite. In people who are overweight or have obesity, the drug promotes substantial weight loss3.

In a talk on 4 March, researchers at the Centers for AIDS Research Network of Integrated Clinical Systems, a group of HIV clinics across the United States, described their analysis of semaglutide use by 222 individuals receiving HIV care. The drug was associated with an average weight loss of 6.5 kilograms in around one year, or 5.7% of initial body weight.

Helping a fatty liver

Antiretroviral therapies have also been associated with abnormal fat accumulation. One condition affecting 30–40% of people with HIV is metabolic dysfunction-associated steatotic liver disease, which is characterized by the build-up of fat in the liver. As the condition progresses, it can result in liver failure and cardiovascular disease. “We do know that people with HIV have a more aggressive form of fatty liver disease,” says Jordan Lake, an infectious-disease physician at the University of Texas Health Science Center at Houston. But there is currently no approved medication to treat the condition.

She and her colleagues evaluated the use of a weekly injection of semaglutide for around six months in people with both HIV and metabolic dysfunction-associated steatotic liver disease. The results, presented on 5 March, demonstrated that 29% of participants had a complete resolution of the liver disease. “What we saw were really great clinically significant reductions in liver fat even over that short period of time,” Lake said at the conference.

But data from the same study show that participants taking semaglutide lost muscle volume, an effect also observed in other people taking the drug. Individuals who were 60 years of age or older were affected the most. Lee notes that older individuals with HIV are especially vulnerable to semaglutide-linked muscle loss and should be followed closely by health-care providers.

Taming inflammation

Another talk at the conference examined the use of semaglutide for a condition called lipohypertrophy in people with HIV. Characterized by the accumulation of abdominal fat, it “is associated with increased inflammation and carries an increased cardiometabolic risk”, says Allison Eckard, an infectious-disease paediatrician at the Medical University of South Carolina in Charleston. “We have currently few treatments and those treatments often show ineffective response rates.”

In an earlier clinical trial, Eckard and her colleagues scanned the bodies of people with HIV and lipohypertrophy and found that semaglutide helped to reduce abdominal fat. They had presented results from that study in October at IDWeek, a meeting of infectious-disease specialists and epidemiologists in Boston, Massachusetts. And at the conference in Denver, the team showed that a blood marker of inflammation called C-reactive protein fell by almost 40% in study participants who took semaglutide compared with those who did not.

That could be an important effect, because even well-controlled HIV leads to a chronic state of inflammation, Lee says. And, he says, “if there’s increased inflammation, it can lead to end-organ disease of all sorts, including certainly cardiovascular outcomes, but also liver, kidney, brain, cognitive function, you name it”.

[ad_2]

Source Article Link

Categories
News

Does The Certo Drug Test Hack Work?

People used to discuss simple home remedies that could be used to pass drug tests in the past. This includes the Certo drug test exploit. What is it, and does it work to pass a urine drug test? Consider this a comprehensive guide and answer the questions because it contains all the required information.

Related: Alpha Brain Review: Does It Really Work

What is The Certo Detox Method?

Cannabis metabolites differ from most other drug waste products. Because of the structure of the cells, they adhere to fat cells in the body. This means they detach erratically and remain in the urine longer. Study data shows a maximum of four months after the last cigarette for chronic smokers.

As a result of their attachment to fat cells, more cannabis metabolites are eliminated through the intestine. Almost all drug detritus is eliminated almost exclusively through urine. Approximately sixty percent of cannabis metabolites are eliminated via the intestine and forty percent via the urine.

What is the science behind it?

The Certo method’s science is based on fruit pectin being a fiber. By consuming it, you produce bile and draw more fat into your bowel, where the cannabis metabolites bind. Furthermore, you are flushing the body with a massive amount of water, which should aid in evacuating the remaining ones via urine.

Is it necessary to use Certo / Sure Jell?

Certo is a fruit pectin brand. It is a fibrous, viscous, fruity liquid used in cooking. That is why it is often referred to as the Sure Jell drug test procedure. Sure Jell is another brand of fruit pectin made in the United States.

You can use any fruit pectin you choose, and buying a generic supermarket brand is cheaper. Fruit pectin is a high-fiber substance. In reality, any fibrous liquid would suffice. However, fruit pectin is inexpensive, and when mixed with water, the volume of water also acts to wash out the bladder.

How To Use Certo To Pass A Drug Test

Certo drug test method instructions are straightforward; you’ll only need to put a few items in place and ensure you do them at the appropriate times before and on your test day.

If you want to give it a try, here is the full Certo detox method laid out for you. You’ll need the following ingredients to do the Certo drug test hack:

  • 2 sachets of Certo, sure jell, or similar fruit pectin
  • 2 bottles of Gatorade or a similar energy drink
  • Aspirin
  • Multivitamin
  • 10 g creatine

Follow these steps after you acquire all the above mentioned:

  • On the evening before your test, mix up one packet of Certo with a bottle of Gatorade. Drink it down in five minutes.
  • Wait 15 minutes, and then consume 16 ounces of water over the course of 30 minutes. Try to excrete twice or thrice prior to bedtime.
  • First thing on the morning of your drug test, at least six hours before it, you’ll take the following steps:
  • Mix the second bottle of Gatorade in with the second sachet of Certo/Sure Jell and drink in five minutes.
  • Then drink 8 fluid ounces of water with one of the aspirin tablets.
  • Drink another eight fluid ounces of water, squash, or juice four hours later, a few hours before your test. Mix in the creatine monohydrate, and drink it while taking the second aspirin and vitamin tablets.
  • Then, over the next hour, urinate several times to push out all of the old urine containing toxins.
  • Get a home drug test kit as an insurance policy and use it right before you depart. If you continue to test positive, you are in trouble, and the Certo technique did not work for you.
Syringe with glass vials and medications pills drug test report

Read: Glucoberry Reviews: Dosage and Side Effects Risk. Does It Work?

Why Gatorade?

Gatorade (and comparable sports drinks) contain many sugars, dextrose, and carbohydrates. The hypothesis is that this increases blood sugar, which inhibits fat metabolism. As a result, the movement of THC metabolites from the intestine to the urine is delayed.

Does The Certo Detox Work For A Urine Test?

Although this can pull out more cannabis metabolites through the intestines and speed up the elimination of cannabis toxins, it cannot eliminate all of them. Consequently, you must consider whether you can flush them out for a sufficient amount of time and maintain the pH balance of your urine by taking multivitamins and creatine.

At the same time, aspirin may produce a false negative. It could succeed. The science exists. However, it only functions for cannabis metabolites. In addition, you have a 75% likelihood of success.

Methods To Pass A Urine Drug Test

As you can see, the Sure Jell exploit is incredibly risky and should be used only under extreme circumstances. There are, fortunately, three excellent strategies you can employ to have a perfect chance of passing a drug test. With the three outline techniques, the success rate is greater than 90 percent and, with a touch of luck, close to 100 percent. These strategies are:

1. Synthetic Urine

By submitting a wholly fake sample, you are not risking your urine being tested. Quick Luck and Sub Solution are the two finest available brands. Quick Luck is superior but it is costly at $100. However, you receive the most complex formula on the market that will pass any scrutiny for your investment.

2. Detox Drinks

A detox drink can be used to disguise the toxins for a few hours before a drug test for meth or any other substance. The best-quality ones are Rescue Cleanse and Mega Clean (be sure to get them with the complimentary pre-rid pills).

They will flood the body with urine-derived substances, causing some to pass through as waste while the balance appears natural. A high-quality detox drink will keep your pee toxin-free for roughly three hours. You can, however, increase this by one or two hours by performing a 24- or 48-hour detox in the days preceding the test.

3. Accelerated Full Body Detox Using Detox Pills

The best way to get free from meth or any other form of drug is to detox naturally. However, this can take weeks. You can speed up the process by taking Toxin Rid detox pills. They are available in course lengths ranging from one day to ten days. If you are a heavy user, I recommend starting with the seven-day course.