Israeli scientists gave an artificial molecule they invented to 30 mice suffering from Alzheimer’s — and found that all of them recovered, regaining full cognitive abilities. They stress that this was a small sample of mice and that human testing is far off, but believe the result indicates that within a decade, their synthetic molecule could be developed into a drug for treating the degenerative disease. The peer-reviewed research, led by neuroscientists from Ben-Gurion University, was recently published in the journal Translational Neurodegeneration.

“We are taking a very different approach than efforts at Alzheimer’s medicines that we have seen so far,” Prof. Varda Shoshan-Barmatz, the lead author, told The Times of Israel. “Most are trying to address plaque that forms in the brain, but we are addressing dysfunction elsewhere. And we’re optimistic. Mice who had Alzheimer’s and received our molecule and then underwent tests had the same cognitive abilities as mice who’d never had Alzheimer’s.”

Interestingly, the molecule appears to have been effective without significantly reducing the amount of plaque, which she thinks indicates that scientists may have been overly fixated on the plaque. There is scientific literature on the dysfunction of mitochondria among people with Alzheimer’s. Mitochondria are organelles — tiny miniature organs within cells — that provide the cell with power. Scientists believe that when they malfunction and fail to produce the normal quantities of energy, it can lead to cell death, inflammation and reduced immune response.

Despite Alzheimer’s being linked to mitochondrial dysfunction, no drug candidates are currently focused on mitochondria. Drug research is mostly concerned with combatting the buildup of protein fragments between nerve cells in the brain, which are thought to be linked to Alzheimer’s. The Ben-Gurion University team set out to normalize mitochondrial activity by countering the harmful effects that occur when a protein called VDAC1 is over-produced. The protein plays a crucial role in regulating the metabolic and energetic functions of mitochondria when produced in normal quantities. But the scientists found that it is produced in huge levels in the brains of mice with Alzheimer’s, and interferes with mitochondrial activity.

“In our research, we have shifted the focus of Alzheimer’s treatments from the plaque to this protein, which is produced in the nerve cells around the plaque instead,” said Shoshan-Barmatz. “We prevent this protein from causing cell death, as the molecule interferes with its harmful effect.”

Source: https://in.bgu.ac.il/ 
AND
https://www.timesofisrael.com/

A team of researchers led by The University of Texas MD Anderson Cancer Center has developed a novel delivery system for messenger RNA (mRNA) using extracellular vesicles (EVs). The new technique has the potential to overcome many of the delivery hurdles faced by other promising mRNA therapies.
In the study, published today in Nature Biomedical Engineering, the researchers use EV-encapsulated mRNA to initiate and sustain collagen production for several months in the cells of photoaged skin in laboratory models. It is the first therapy to demonstrate this ability and represents a proof-of-concept for deploying the EV mRNA therapy.

“This is an entirely new modality for delivering mRNA,” said corresponding author Betty Kim, M.D., Ph.D., professor of Neurosurgery. “We used it in our study to initiate collagen production in cells, but it has the potential to be a delivery system for a number of mRNA therapies that currently have no good method for being delivered.”
The genetic code for building specific proteins is contained in mRNA but delivering mRNA within the body is one of the largest hurdles facing clinical applications of many mRNA-based therapies. The current COVID-19 vaccines, which marked the first widespread use of mRNA therapy, use lipid nanoparticles for delivery, and the other primary delivery systems for genetic materials so far have been viral based. However, each of these approaches comes with certain limitations and challenges.

Extracellular vesicles are small structures created by cells that transport biomolecules and nucleic acids in the body. These naturally occurring particles can be modified to carry mRNAs, which gives them the benefit of innate biocompatibility without triggering a strong immune response, allowing them to be administered multiple times. Additionally, their size allows them to carry even the largest human genes and proteins.

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An experimental vaccine against breast cancer safely generated a strong immune response to a key tumor protein, researchers from the University of Washington (UW) School of Medicine in Seattle report in a paper published by the journal JAMA Oncology. The findings suggest the vaccine may be able to treat different types of breast cancer.

“Because this was not a randomized clinical trial, the results should be considered preliminary, but the findings are promising enough that the vaccine will now be evaluated in a larger, randomized clinical trial,” said lead author Dr. Mary “Nora” L. Disis, a UW professor of medicine, Division of Medical Oncology, and director of the Cancer Vaccine Institute.

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Research headed by scientists at the National Institute of Dental and Craniofacial Research (NIDCR) has shown how blocking the function of the blood clotting protein, fibrin, prevents bone loss from periodontal (gum) disease in mice. Drawing on animal and human data, the study—headed by NIDCR investigators Niki Moutsopoulos, DDS, PhD, and Thomas Bugge, PhD, found that build-up of fibrin triggers an overactive immune response that damages the gums and underlying bone. The results suggest that suppressing abnormal fibrin activity could hold promise for preventing or treating periodontal disease, as well as other inflammatory disorders—including arthritis and multiple sclerosis—that are marked by fibrin buildup.

”Severe periodontal disease can lead to tooth loss and remains a barrier to productivity and quality of life for far too many Americans, especially those lacking adequate access to dental care,” said NIDCR director Rena D’Souza, DDS, PhD. “By providing the most comprehensive picture yet of the underlying mechanisms of periodontal disease, this study brings us closer to more effective methods for prevention and treatment.”

Periodontal disease is a bacterial infection of the tissues supporting the teeth. The condition affects nearly half of people in the United States who are over the age 30, and 70% of those who are 65 years and older. In its early stages, periodontal disease causes redness and swelling (inflammation) of the gums. In advanced stages, called periodontitis, the underlying bone becomes damaged, leading to tooth loss. While scientists have known that periodontitis is driven in part by an exaggerated immune cell response, until now, it was unclear what triggered the response, and how it caused tissue and bone damage.

Moutsopoulos, Bugge, and colleagues reported their findings in Science, in a paper titled, “Fibrin is a critical regulator of neutrophil effector function at the oral mucosal barrier.”

Source: https://www.genengnews.com/

An experimental HIV vaccine that uses the same technology as the COVID-19 mRNA vaccines from Moderna and Pfizer is showing promising results in both monkeys and mice. A press release from the National Institute of Allergy and Infectious Diseases (NIAID) explained that monkeys who received a multiple doses of the experimental vaccine had their chances of contracting an HIV-like virus lowered by 79%.

Scientists have spent decades struggling to create an HIV vaccine due to the speed at which the virus mutates and its remarkable ability to evade the immune system. Dr. Anthony Fauci, president of NIAID, leader of the United States’ battle against COVID-19, and a co-author of this HIV vaccine study published in Nature Medicine, expressed optimism about the progress made by the mRNA technology.

“Despite nearly four decades of effort by the global research community, an effective vaccine to prevent HIV remains an elusive goal,” Fauci said. “This experimental mRNA vaccine combines several features that may overcome shortcomings of other experimental HIV vaccines and thus represents a promising approach.”

The trial involved a series of booster shots in macaques over the course of an entire year. The authors explained that not only did the trial yield a positive immune response, but also that “the vaccine was well tolerated with only mild adverse events after each inoculation,” with the most common side effect being loss of appetite.

Now the researchers are working on refining the process so less rounds of shots are needed, as they noted in Nature Medicine that “a vaccination regimen encompassing seven or more sequential immunizations would be difficult to implement in humans.” The study’s leader Dr. Paolo Lusso, said that if the team is successful at reducing the number of boosters in a safe and effective way, they will then move on to a phase 1 trial of the vaccine in adult humans.

Source: https://www.lgbtqnation.com/

The Omicron variant substantially reduced antibody levels generated by the Pfizer-BioNTech COVID-19 vaccine, according to preliminary results from a South African study that’s still awaiting peer review. These are the first laboratory results to see how a COVID-19 vaccine holds up to Omicron. A team of researchers led by Africa Health Research Institute‘s Alex Sigal tested 14 blood samples from 12 people against a live sample of the Omicron variant. All 12 people were vaccinated, and six were previously infected.

Overall, the scientists found a roughly 40-fold reduction in the levels of neutralizing antibodies, the virus-fighting proteins that play a key role in our immune response, compared with the original version of the virus. Omicron did not evade vaccine protection completely, Sigal wrote on Twitter, meaning there’s still benefit to being vaccinated against this new variant. But the marked reduction in antibodies raises questions of how durable vaccine protection will be against Omicron – namely, whether booster shots will sufficiently ward off disease or if new vaccines may eventually be required. Sigal called it a “very large drop in neutralization of Omicron.”

“A good booster probably would decrease your chance of infection, especially severe infection leading to more severe disease,” Sigal said in an online presentation of his results on Tuesday, according to Bloomberg. “People who haven’t had a booster should get one, and people who have been previously infected should be vaccinated.”

Shortly after Sigal announced his team’s results, another group of researchers at Sweden‘s Karolinska Institutet disclosed their own findings that suggested a substantial but less dramatic decline in antibody levels. The Karolinska team found a seven-fold reduction across 17 blood samples. They noted the impact of Omicron varied greatly between samples, and they used a version of Omicron that was artificially made in a lab instead of the live virus. A lead researcher for that group said the findings make Omicron “certainly worse than Delta, but, again, not as extreme as we expected.” The results are not finalized and have not been published in a medical journal. Sigal cautioned on Twitter that the findings “are likely to be adjusted as we do more experiments.”

Source: https://www.sciencealert.com/

The study also showed that a novel natural antiviral drug called thapsigargin (TG), recently discovered by the same group of scientists to block other viruses, including the original SARS-CoV-2, was just as effective at treating all of the newer SARS-CoV-2 variants, including the Delta variant.

In their previous studies* the team showed that the plant-derived antiviral, at small doses, triggers a highly effective broad-spectrum host-centred antiviral innate immune response against three major types of human respiratory viruses, including SARS-CoV-2.

In this latest study, the team set out to find out how well the emergent Alpha, Beta and Delta variants of SARS-CoV-2 are able to multiply in cells relative to each other as single variant infections and in co-infections– where cells are infected with two variants at the same time. The team also wanted to know just how effective TG was at blocking these emergent variants. Notably, all SARS-CoV-2 variants were highly susceptible to TG treatment. A single pre-infection priming dose of TG effectively blocked all single-variant infections and every co-infection at greater than 95% relative to controls. Likewise, TG was effective in inhibiting each variant during active infection.

Source: https://www.nottingham.ac.uk/

Brigham and Women’s Hospital will test the safety and efficacy of a nasal vaccine aimed at preventing and slowing Alzheimer’s disease, the Boston hospital announced Tuesday. The start of the small, Phase I clinical trial comes after nearly 20 years of research led by Howard L. Weiner, MD, co-director of the Ann Romney Center for Neurologic Diseases at the hospital.

The trial will include 16 participants between the ages of 60 and 85, all with early symptomatic Alzheimer’s but otherwise generally healthy. They will receive two doses of the vaccine one week apart, the hospital said in a press release. The participants will enroll from the Ann Romney Center.

A Phase I clinical trial is designed to establish the safety and dosage for a potential new medication. If it goes well, a much larger trial would be needed to test its effectiveness. The vaccine uses a substance called Protollin, which stimulates the immune system. “Protollin is designed to activate white blood cells found in the lymph nodes on the sides and back of the neck to migrate to the brain and trigger clearance of beta amyloid plaques — one of the hallmarks of AD [Alzheimer’s disease],” the hospital explains. It notes that Protollin has been found to be safe in other vaccines.

“The launch of the first human trial of a nasal vaccine for Alzheimer’s is a remarkable milestone,” said Weiner in the hospital’s press release. “Over the last two decades, we’ve amassed preclinical evidence suggesting the potential of this nasal vaccine for AD. If clinical trials in humans show that the vaccine is safe and effective, this could represent a nontoxic treatment for people with Alzheimer’s, and it could also be given early to help prevent Alzheimer’s in people at risk.”

The researchers say they aim to “determine the safety and tolerability of the nasal vaccine” in the trial and observe how Protollin affects participants’ immune response, including how it affects their white blood cells.

“The immune system plays a very important role in all neurologic diseases,” Weiner added. “And it’s exciting that after 20 years of preclinical work, we can finally take a key step forward toward clinical translation and conduct this landmark first human trial.”

Source: brighamandwomens.org
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https://www.cbsnews.com/

Until recently, most of the world had never heard of mRNA vaccines. To combat COVID-19, the United States Food and Drug Administration issued emergency use authorization in December 2020 for mRNA vaccines developed by Pfizer-BioNTech and Moderna. While the pandemic brought mRNA vaccines into the limelight, melanoma patient Bobby Fentress had experience with mRNA technology nearly a year prior. mRNA vaccines hold promise for fighting infectious diseases beyond the SARS-CoV-2 virus, including fighting cancer. At age 68, Bobby was an early participant in a clinical trial intended to see whether a vaccine made with mRNA could destroy his cancer cells and prevent recurrence.

Bobby’s story began in 2019. He found an odd bump on his middle finger and assumed it was a wart. After his wife urged him to be seen by a dermatologist, he received a call that he would need a biopsy – which ultimately revealed that he had stage 2c melanoma. Several months later, Bobby had most of his middle finger amputated and was told that there was a 50% possibility that the cancer would reoccur.  That’s when Bobby decided to enroll in a clinical trial with HCA Healthcare’s Sarah Cannon Research Institute in Nashville, Tennessee. He received his first shots of a personalized mRNA vaccine created by Moderna in April 2020. These vaccines are developed from a patient’s specific tumor DNA. The DNA of the tumor is analyzed to determine the differences between the tumor and a patient’s own cells and which proteins might elicit the best immune response. The mRNA vaccine is then developed to instruct the body to make these proteins and stimulate an immune response. Patients such as Bobby then receive a series of these vaccine treatments.

“Bobby finished his year of treatment earlier this spring. While it is too early to know if the therapy will work, Bobby’s oncologist, Dr. Meredith McKean, is optimistic.  Immunotherapy has been a game changer for melanoma. With mRNA, the hope is that personalized therapy would offer additional treatment benefit above our standard treatments that we offer for patients broadly. Even for patients like Bobby that had surgery, ten years ago we wouldn’t be able to give him anything but highly toxic therapy options. It’s refreshing to offer a clinical trial like this. While the trial is not yet complete, we have enough data to be hopeful. It’s a very encouraging area that I’m excited about as a provider,” says Dr McKean, associate director of the melanoma and skin cancer research program at Sarah Cannon Research Institute.

https://hcahealthcaretoday.com/

Across the world, health care workers and high-risk groups are beginning to receive COVID-19 vaccines, offering hope for a return to normalcy amidst the pandemic. However, the vaccines authorized for emergency use in the U.S. require two doses to be effective, which can create problems with logistics and compliance. Now, researchers reporting in ACS Central Science have developed a nanoparticle vaccine that elicits a virus-neutralizing antibody response in mice after only a single dose.

The primary target for COVID-19 vaccines is the spike protein, which is necessary for SARS-CoV-2’s entry into cells. Both of the vaccines currently authorized in the U.S. are mRNA vaccines that cause human cells to temporarily produce the spike protein, triggering an immune response and antibody production.

Peter Kim and colleagues wanted to try a different approach: a vaccine consisting of multiple copies of the spike protein displayed on ferritin nanoparticles. Ferritin is an iron storage protein found in many organisms that self-assembles into a larger nanoparticle. Other proteins, such as viral antigens, can be fused to ferritin so that each nanoparticle displays several copies of the protein, which might cause a stronger immune response than a single copy.

The researchers spliced spike protein and ferritin DNA together and then expressed the hybrid protein in cultured mammalian cells. The ferritin self-assembled into nanoparticles, each bearing eight copies of the spike protein trimer. The team purified the spike/ferritin particles and injected them into mice. After a single immunization, mice produced neutralizing antibody titers that were at least two times higher than those in convalescent plasma from COVID-19 patients, and significantly higher than those in mice immunized with the spike protein alone. A second immunization 21 days later produced even higher antibody levels. Although these results must be confirmed in human clinical trials, they suggest that the spike/ferritin nanoparticles may be a viable strategy for single-dose vaccination against COVID-19, the researchers say.

Source: https://www.acs.org/