Successful Transplant of Porcine Heart into Adult Human

In a first-of-its-kind surgery, a 57-year-old patient with terminal heart disease received a successful transplant of a genetically-modified pig heart and is still doing well three days later. It was the only currently available option for the patient. The historic surgery was conducted by University of Maryland School of Medicine (UMSOM) faculty at the University of Maryland Medical Center (UMMC), together known as the University of Maryland Medicine.

This organ transplant demonstrated for the first time that a genetically-modified animal heart can function like a human heart without immediate rejection by the body. The patient, David Bennett, a Maryland resident, is being carefully monitored over the next days and weeks to determine whether the transplant provides lifesaving benefits. He had been deemed ineligible for a conventional heart transplant at UMMC as well as at several other leading transplant centers that reviewed his medical records.

 “It was either die or do this transplant. I want to live. I know it’s a shot in the dark, but it’s my last choice,” said Mr. Bennett, the patient, a day before the surgery was conducted. He had been hospitalized and bedridden for the past few months.  I look forward to getting out of bed after I recover.

The U.S. Food and Drug Administration granted emergency authorization for the surgery on New Year’s Eve through its expanded access (compassionate use) provision. It is used when an experimental medical product, in this case the genetically-modified pig’s heart, is the only option available for a patient faced with a serious or life-threatening medical condition. The authorization to proceed was granted in the hope of saving the patient’s life.

“This was a breakthrough surgery and brings us one step closer to solving the organ shortage crisis. There are simply not enough donor human hearts available to meet the long list of potential recipients,” said Bartley P. Griffith, MD, who surgically transplanted the pig heart into the patient. Dr. Griffith is the Thomas E. and Alice Marie Hales Distinguished Professor in Transplant Surgery at UMSOM. “We are proceeding cautiously, but we are also optimistic that this first-in-the-world surgery will provide an important new option for patients in the future.”

Considered one of the world’s foremost experts on transplanting animal organs, known as xenotransplantation, Muhammad M. Mohiuddin, MD, Professor of Surgery at UMSOM, joined the UMSOM faculty five years ago and established the Cardiac Xenotransplantation Program with Dr. Griffith. Dr. Mohiuddin serves as the program’s Scientific/Program Director and Dr. Griffith as its Clinical Director.

“This is the culmination of years of highly complicated research to hone this technique in animals with survival times that have reached beyond nine months. The FDA used our data and data on the experimental pig to authorize the transplant in an end-stage heart disease patient who had no other treatment options,” said Dr. Mohiuddin.The successful procedure provided valuable information to help the medical community improve this potentially life-saving method in future patients.

Source: https://www.medschool.umaryland.edu/

Viagra Users Are 69% Less Likely to Develop Alzheimer’s

Viagra could be a useful treatment against Alzheimer’s disease, according to a US study. Alzheimer’s disease, the most common form of age-related dementia, affects hundreds of millions of people worldwide. Despite mounting numbers of cases, however, there is currently no effective treatment.

Using a large gene-mapping network, researchers at the Cleveland Clinic integrated genetic and other data to determine which of more than 1,600 Food and Drug Administration-approved drugs could be an effective treatment for Alzheimer’s disease. They gave higher scores to drugs that target both amyloid and tau – two hallmarks of Alzheimer’s – compared with drugs that targeted just one or the other.

US scientists say users of sildenafil – the generic name for Viagra – are 69% less likely to develop the form of dementia than non-users

“Sildenafil, which has been shown to significantly improve cognition and memory in preclinical models, presented as the best drug candidate,” said Dr Feixiong Cheng, the study lead.

Researchers then used a database of claims from more than 7 million people in the US to examine the relationship between sildenafil and Alzheimer’s disease outcomes by comparing sildenafil users to non-users.

They found sildenafil users were 69% less likely to develop Alzheimer’s disease than non-sildenafil users after six years of follow-up. To further explore the drug’s potential effect on Alzheimer’s disease, researchers developed a lab model that showed that sildenafil increased brain cell growth and targeted tau proteins, offering insights into how it might influence disease-related brain changes. Cheng cautioned that the study does not demonstrate a causal relationship between sildenafil and Alzhemer’s disease. Randomised clinical trials involving both sexes with a placebo control were needed to determine sildenafil’s efficacy, he said.

Dr Ivan Koychev, a senior clinical researcher at the University of Oxford, who was not involved in the study, said it was “an exciting development” because “it points to a specific drug which may offer a new approach to treating the condition”.

Prof Tara Spires-Jones, deputy director of the Centre for Discovery Brain Sciences at the University of Edinburgh, said there were several important limitations to consider. “While these data are interesting scientifically, based on this study, I would not rush out to start taking sildenafil as a prevention for Alzheimer’s disease.”

Dr Susan Kohlhaas, director of research at Alzheimer’s Research UK, said: “Being able to repurpose a drug already licensed for other health conditions could help speed up the drug discovery process and bring about life-changing dementia treatments sooner. “Importantly, this research doesn’t prove that sildenafil is responsible for reducing dementia risk, or that it slows or stops the disease. The only way to test this would be in a large-scale clinical trial measuring sildenafil effect against the usual standard of care.”

The findings were published in Nature Aging.

Source: https://www.theguardian.com/

Pfizer CEO: “Very High Level of Confidence” that the Covid Treatment Pill Is Effective Against the Omicron Variant

Pfizer CEO Albert Bourla said he expects the company’s Covid-19 treatment pill to be effective against the omicron variant of the virus causes Covid-19.

The good news when it comes to our treatment, it was designed with that in mind, it was designed with the fact that most mutations are coming in the spikes,” Bourla explained.  “So that gives me very high level of confidence that the treatment will not be affected, our oral treatment will not be affected by this virus.”

Pfizer submitted its application earlier this month to the Food and Drug Administration (FDA) to authorize the pill, Paxlovid, for emergency use. In a clinical trial of people age 18 and over, Pfizer found the pill reduces hospitalization and death by 89% when taken with a widely used HIV drug within three days of the start of symptoms. The pill blocks an enzyme the virus needs to replicate. It is used in combination with HIV drug ritonavir, which slows the human metabolism to allow the Paxlovid to remain active in the body longer at a higher concentration to combat the virus.

https://www.cnbc.com/

Virtual Reality System to Ease Back Pain

A 3-D virtual reality system to treat back pain was approved by the U.S. Food and Drug Administration (FDA) this week. The EaseVRx system is a prescription device for at-home use that combines cognitive behavioral therapy and other behavioral methods to treat patients 18 and older with chronic lower back pain.

Millions of adults in the United States are living with chronic lower back pain that can affect multiple aspects of their daily life,” said Dr. Christopher Loftus, acting director of the Office of Neurological and Physical Medicine Devices in the FDA‘s Center for Devices and Radiological Health.

Pain reduction is a crucial component of living with chronic lower back pain. Today’s authorization offers a treatment option for pain reduction that does not include opioid pain medications when used alongside other treatment methods for chronic lower back pain,” Loftus said in an agency news release.

A treatment program includes 56 VR sessions that are 2 to 16 minutes long as part of a daily eight-week treatment program. The FDA approval is based on a clinical trial that included 179 patients with chronic lower back pain assigned to one of two eight-week VR programs: the EaseVRx 3-D program or a control 2-D program that did not feature CBT methods.

At the end of treatment, 66% of EaseVRx participants reported a greater than 30% reduction in pain, compared to 41% of those in the control groupA greater than 50% pain reduction was reported by 46% of the EaseVRx users, compared with 26% of those in the control group, according to the FDA.

One, two and three months after treatment, all EaseVRx users still reported a 30% reduction in pain, which was higher than in the control group. Nearly 21% of EaseVRx users reported discomfort with the headset and about 10% reported motion sickness and nausea, but there were no serious side effects associated with the system, which is made by AppliedVR.

Source:  https://www.upi.com/

The Drugmaker Merck Says Its Antiviral Pill Is Effective Against Coronavirus

The drug maker says its pill was shown in a clinical trial to cut the risk of hospitalization or death from the virus in half. Australia is accelerating plans to ease international travel restrictions for its citizens and permanent residents.

The drug maker Merck said on Friday that it would seek authorization for the first antiviral pill for Covid after its drug, known as molnupiravir, was shown in a clinical trial to cut the risk of hospitalization or death in half when given to high-risk people early in their infections.

The treatment could become the first in a wave of antiviral pill products, which experts say could offer a powerful new tool in efforts to tame the pandemic, as they could reach more people than the antibody treatments that are being widely used in the United States for similar patients.

I think it will translate into many thousands of lives being saved worldwide, where there’s less access to monoclonal antibodies, and in this country, too,” said Dr. Robert Shafer, an infectious disease specialist and expert on antiviral therapy at Stanford University.

Late-stage study results of two other antiviral pills, one developed by Pfizer and the other by Atea Pharmaceuticals and Roche, are expected within the next few months.

The Merck drug, which is designed to stop the coronavirus from replicating, is to be taken as four capsules twice a day for five days.

Merck said an independent board of experts monitoring its study data had recommended that its trial be stopped early because the drug’s benefit to patients had proved so convincing. The company said that the Food and Drug Administration had agreed with that decision.

For the research, the monitors looked at data through early August, when the study had enrolled 775 volunteers in the United States and overseas. For volunteers who received the drug, their risk of being hospitalized or dying fell 50 percent, without any concerning side effects, compared with those who received placebo pills, Merck said in a news release announcing the findings.

Seven percent of volunteers in the group that received the drug were hospitalized, and none of them died, compared with a 14 percent rate of hospitalization and death — including eight deaths — in the group that received the placebo.

The Merck pill’s efficacy was lower than that of monoclonal antibody treatments, which mimic antibodies that the immune system generates naturally when fighting the virus. Those drugs have been in high demand recently, but they are expensive, are typically given intravenously, and have proved cumbersome and labor-intensive for hospitals and clinics to administer. Studies have shown that they reduce hospitalizations and deaths 70 to 85 percent in similar high-risk Covid patients.

Source: https://www.nytimes.com/

FDA-approved Drugs Slow or Reverse Alzheimer’s

A research team at Washington University School of Medicine in St. Louis has identified potential new treatment targets for Alzheimer’s disease, as well as existing drugs that have therapeutic potential against these targets.

The potential targets are defective proteins that lead to the buildup of amyloid in the brain, contributing to the onset of problems with memory and thinking that are the hallmark of Alzheimer’s. The 15 existing drugs identified by the researchers have been approved by the Food and Drug Administration (FDA) for other purposes, providing the possibility of clinical trials that could begin sooner than is typical, according to the researchers.

In addition, the experiments yielded seven drugs that may be useful for treating faulty proteins linked to Parkinson’s disease, six for stroke and one for amyotrophic lateral sclerosis (ALS).

Scientists have worked for decades to develop treatments for Alzheimer’s by targeting genes rooted in the disease process but have had little success. That approach has led to several dead ends because many of those genes don’t fundamentally alter proteins at work in the brain. The new study takes a different approach, by focusing on proteins in the brain, and other tissues, whose function has been altered.

In this study, we used human samples and the latest technologies to better understand the biology of Alzheimer’s disease,” said principal investigator Carlos Cruchaga, the Reuben Morriss III Professor of Neurology and a professor of psychiatry. “Using Alzheimer’s disease samples, we’ve been able to identify new genes, druggable targets and FDA-approved compounds that interact with those targets to potentially slow or reverse the progress of Alzheimer’s.”

The scientists focused on protein levels in the brain, cerebrospinal fluid (CSF) and blood plasma of people with and without Alzheimer’s disease. Some of the proteins were made by genes previously linked to Alzheimer’s risk, while others were made by genes not previously connected to the disease. After identifying the proteins, the researchers compared their results to several databases of existing drugs that affect those proteins.

The new study, funded by the National Institute on Aging of the National Institutes of Health (NIH), is published in the journal Nature Neuroscience.

Source: https://source.wustl.edu/

New promising Cancer Treatment

The recent approval of Lumakras (Amgen, AMG 510) by the US Food and Drug Administration as a treatment for non-small cell lung cancer is a breakthrough in cancer therapy. The drug acts as an irreversible inhibitor of KRAS, a mutant protein common to many troubling tumors, including lung, pancreatic and colorectal cancers.

KRAS has been the Moby Dick of cancer therapy. Over the last forty years, its elusive nature has stymied generations of drug developers. Discovered in 1983, it was one of the very first oncogenes ever identified. An oncogene is the mutated form of a normal human gene that often lies at the very origin of many cancers. KRAS is present in 32% of non-small cell lung cancers, 40% of colorectal cancers, and 85% to 90% of pancreatic cancers.

The normal cellular KRAS protein plays a central role in healthy cells by acting as an on/off switch for cell growth. KRAS is activated by binding to guanosine triphosphate (GTP). Once activated, the KRAS protein signals the cell to grow and divide. It is turned off when it converts GTP to guanosine diphosphate (GDP). The mutation that transforms KRAS into an oncogene locks the protein into an active state, permanently bound to GTP, causing cells to grow uncontrollably.

Why has KRAS been such a difficult problem to solve? Most drugs work by binding to sites within the crevices in a protein structure. According to Victor Cee, a research scientist formerly with Amgen,

There’s almost nowhere that a drug can stick to on that protein.” After screening a subset of chemicals, the team of researchers from Amgen found one that weakly bound to the KRAS molecule resting in a shallow pocket of the protein near the GDP binding site. Structural analysis showed that entry to a deeper crevice below was blocked by a histidine residue. Eventually, they found a family of drugs that could displace the histidine, thus allowing entry to the deeper cleft. Binding to this site alters the conformation of the nearby GDP binding site, fixing the GDP in place and permanently locking KRAS in the inactivated position.

Source: https://www.forbes.com/

Anti-diabetic Medication at a Specific Dosage Makes you Loose Weight

A weight-loss drug described as a ‘game-changer by obesity researchers has just been approved by the US Food and Drug Administration (FDA), representing the first time the agency has endorsed such a treatment in several years. Wegovy, a weight-management therapy to be manufactured by Danish pharmaceutical company Novo Nordisk, is the the first FDA-approved weight-loss drug since 2014, but it’s not entirely a new medication.

The same drug, called semaglutide, has been used in the US and other countries as an anti-diabetic medication for years. More recently, however, evidence has shown that semaglutide at a different dosage also functions as a powerful and effective appetite-suppressant. In a study published earlier in the year involving almost 2,000 obese adults from 16 different countries, researchers reported that long-term treatment with the medicine led to almost 15 percent weight loss on average across the cohort.

Some lost even more, with over 30 percent of the group dropping in excess of 20 percent of their body weight – results that the scientists singled out as remarkable.

No other drug has come close to producing this level of weight loss – this really is a game-changer,” obesity researcher Rachel Batterham from University College London said at the time.

For the first time, people can achieve through drugs what was only possible through weight-loss surgery.”

Source: https://www.sciencealert.com/

F.D.A. Approves Alzheimer’s Drug

Aducanumab, or Aduhelm, is the first new Alzheimer’s treatment in 18 years and the first to attack the disease process. But some experts say there’s not enough evidence it can address cognitive symptomsThe Food and Drug Administration  approved the first new medication for Alzheimer’s disease in nearly two decades, a contentious decision made despite opposition from the agency’s independent advisory committee and some Alzheimer’s experts who said there was not enough evidence that the drug can help patients.

The drug, aducanumab, which will go by the brand name Aduhelm, is a monthly intravenous infusion intended to slow cognitive decline in people with mild memory and thinking problems. It is the first approved treatment to attack the disease process of Alzheimer’s instead of just addressing dementia symptoms. Biogen, its manufacturer, announced that the list price would be $56,000 a year. In addition, there will most likely be tens of thousands of dollars in costs for diagnostic testing and brain imaging. Recognizing that clinical trials of the drug had provided incomplete evidence to demonstrate effectiveness, the F.D.A. granted approval for the drug to be used but required Biogen to conduct a new clinical trial. If the new trial, called a Phase 4 trial, fails to show the drug is effective, the F.D.A. can — but is not required to — rescind its approval.

About six million people in the United States and roughly 30 million globally have Alzheimer’s, a number expected to double by 2050. Currently, five medications approved in the United States can delay cognitive decline for several months in various Alzheimer’s stages. Patient advocacy groups had lobbied vigorously for approval because there are so few treatments available for the debilitating condition. Some other drugs in clinical trials are more promising, but they are most likely three or four years away from potential approval.

The F.D.A. advisory committee, along with an independent think tank and several prominent experts — including some Alzheimer’s doctors who worked on the aducanumab clinical trials — said the evidence raised significant doubts about whether the drug is effective. They also said that even if it could slow cognitive decline in some patients, the benefit suggested by the evidence would be so slight that it would not outweigh the risk of swelling or bleeding in the brain that the drug caused in the trials.

The data included in the applicant’s submission were highly complex and left residual uncertainties regarding clinical benefit,” the F.D.A.’s director of the Center for Drug Evaluation and Research, Dr. Patrizia Cavazzoni, wrote on the agency’s website. But, she said, the agency had decided to approve the drug through a program called accelerated approval, which is designed “to provide earlier access to potentially valuable therapies for patients with serious diseases where there is an unmet need, and where there is an expectation of clinical benefit despite some residual uncertainty regarding that benefit.” Michel Vounatsos, Biogen’s chief executive, hailed the approval and said in a statement, “We are committed to sharing our future insights about Aduhelm with the scientific community as we collect more data from the real-world use of this treatment.

Source: https://www.nytimes.com/

How to Completely Wipe out Colon Cancer in Anybody Who Gets Screened

Michael Wallace has performed hundreds of colonoscopies in his 20 years as a gastroenterologist. He thinks he’s pretty good at recognizing the growths, or polyps, that can spring up along the ridges of the colon and potentially turn into cancer. But he isn’t always perfect. Sometimes the polyps are flat and hard to see. Other times, doctors just miss them. “We’re all humans,” says Wallace, who works at the Mayo Clinic. After a morning of back-to-back procedures that require attention to minute details, he says, “we get tired.”

Colonoscopies, if unpleasant, are highly effective at sussing out pre-cancerous polyps and preventing colon cancer. But the effectiveness of the procedure rests heavily on the abilities of the physician performing it. Now, the Food and Drug Administration has approved a new tool that promises to help doctors recognize precancerous growths during a colonoscopy: an artificial intelligence system made by Medtronic. Doctors say that alongside other measures, the tool could help improve diagnoses.

 

We really have the opportunity to completely wipe out colon cancer in anybody who gets screened,” says Wallace, who consulted with Medtronic on the project.

The Medtronic system, called GI Genius, has seen the inside of more colons than most doctors. Medtronic and partner Cosmo Pharmaceuticals trained the algorithm to recognize polyps by reviewing more than 13 million videos of colonoscopies conducted in Europe and the US that Cosmo had collected while running drug trials. To “teach” the AI to distinguish potentially dangerous growths, the images were labeled by gastroenterologists as either normal or unhealthy tissue. Then the AI was tested on progressively harder-to-recognize polyps, starting with colonoscopies that were performed under perfect conditions and moving to more difficult challenges, like distinguishing a polyp that was very small, only in range of the camera briefly, or hidden in a dark spot. The system, which can be added to the scopes that doctors already use to perform a colonoscopy, follows along as the doctor probes the colon, highlighting potential polyps with a green box. GI Genius was approved in Europe in October 2019 and is the first AI cleared by the FDA for helping detect colorectal polyps. “It found things that even I missed,” says Wallace, who co-authored the first validation study of GI Genius. “It’s an impressive system.”

Source: https://www.wired.com/