Day: March 9, 2022

Categories : Respiratory DiseasesTags :

Mepolizumab Weans Severe Asthma Patients off Steroids

On By ModernMedia
Asthma inhaler
Source: PIxabay/CC0

In a real world study, patients taking oral corticosteroids for severe asthma, taking mepolizumab reduced the need for those steroids by 75%. These findings were presented at the annual meeting of the American Academy of Allergy, Asthma & Immunology.

By the end study, patients on a median 10 mg maintenance dose of oral corticosteroids at baseline reduced their intake to 2.5 mg, reported Mark Liu, MD, of Johns Hopkins Medicine, who presented the findings.

And those on a median 5 mg maintenance dose at the start of the trial reduced their use to 0.4 mg by study end, Dr Liu said.

In the high steroid dose group, 36% were able to be weaned off the drugs by the end of the study, he reported. In the lower dose group, 49% were able to discontinue steroid use.

Treatment with the interleukin-5 (IL-5) antagonist mepolizumab reduced clinically significant annual exacerbations from a mean of 4.3 in the 12 months prior to the trial to 1.5 with mepolizumab use. This reduction from baseline was seen across all patient groups, said Dr Liu, including those with high and low steroid use and those who were not taking steroids at baseline to control symptoms.

Dr Liu suggested that despite the limitation of being a single-arm study, the “clinically important real-world findings indicate that patients with severe asthma treated with mepolizumab can reduce their oral corticosteroid use, potentially reducing the risk of side effects associated with their use, while improving their asthma control.”

The co-moderator of the presentation session, William Anderson, MD, of Children’s Hospital Colorado, said the study was important – “especially for our adult patients who are on chronic steroids, because the side effects of chronic steroids are so profound and oftentimes can lead to equal if not worse effects than the underlying asthma itself.”

“The ability to use a biologic agent to decrease the dose of an oral steroid for our patients is certainly extraordinarily promising,” Dr Anderson said to MedPage Today. “Our ultimate goal is to get patients off oral steroids.”

For the year-long study, Dr Liu and colleagues enrolled 822 adults with asthma and a new prescription for mepolizumab with at least 12 months of previous medical records. Mepolizumab was given at the standard 100mg subcutaneous dose.

“Patients with severe asthma often rely on oral corticosteroids to control their symptoms despite a well-recognized risk of complications even at low daily doses,” Dr Liu explained. The goal of the study, he said, was to determine what happened in a real-world setting when these patients were treated with mepolizumab, stratified by steroid use. The researchers enrolled patients from December 2016 through October 2019.

About 10% of patients experienced adverse events, but serious adverse events occurred in less than 1%, Dr Liu noted.

Source: MedPage Today

Categories : COVIDTags :

Aspen to Locally Produce COVID Vaccine ‘Aspenovax’ for the African Continent

On By ModernMedia
Syringe withdrawing from vaccine vial
Photo by Mufid Majnun

In a news release, pharma giant Aspen has announced that it has concluded an agreement with Johnson & Johnson to manufacture an Aspen-branded COVID vaccine, Aspenovax, and to make it available throughout Africa.

This follows on from the November 2021 announcement of an agreement of terms between the two companies. This new agreement will expand the existing technical transfer and manufacturing agreements between the companies.

The agreement will grant Aspen’s South African subsidiary the rights to manufacture finished Aspenovax product from drug substance supplied by J&J. It will also make Aspenovax available to markets in Africa through transactions with designated multilateral organisations and with national governments of member states of the African Union.

Under the agreement, Aspen has secured the necessary intellectual property from Johnson & Johnson for production. There is also a good faith undertaking between the companies to expand the agreement to cover any new versions of the drug substance, such as those developed for new variants or a different formulation for administration as a booster.

The agreement will last through to the end of 2026.

Commenting on this agreement, Dr Matshidiso Moeti, World Health Organization Regional Director for Africa said: “This important agreement on sharing know-how and technologies for the production of COVID vaccines is a huge leap forward towards realising our shared vision for medicines and vaccines to be manufactured on the African soil for the African people. Vaccines are our best way out of this pandemic and local production is an essential recipe for our success.”

Stephen Saad, Aspen Group Chief Executive said: “Even with all the support in the world, none of this would be possible without the competence of our teams at Gqeberha. They knew the weight of a continent’s ambitions rested on their shoulders. They persevered and succeeded in becoming a significant supplier within the Johnson & Johnson network. Aspenovax has become a reality due to the confidence placed in their abilities. They are our African heroes.”

Categories : COVID GenderTags :

The Pandemic’s Negative Impact on Women in Academic Medicine

On By ModernMedia
Female scientist in laboratory
Photo by Gustavo Fring from Pexels

Like women in every other sector of the economy, the COVID pandemic has negatively impacted those working in academic medicine according to a commentary which appears in Nature Medicine.

Co-author Anne B. Curtis, MD, professor at the University at Buffalo, laid out the problem: “During the first year of the pandemic, when schools shut down and went to 100% remote learning, we saw that it affected women disproportionately, having to stay home and teach their children while their research languished.”

Even before the COVID pandemic, women in academic medicine were paid less than men in comparable positions, received lower startup funds for laboratory research and were promoted later.

Additionally, they wrote that, compared to men, women have fewer “conventional markers of achievement” in academia, such as principal investigator positions on research grants. Women write fewer grant applications; they have fewer grant renewals; they get lower funding amounts for initial grants; and are first or last author on fewer papers.

The reasons for these are well known, the authors wrote.

“Society expects women to assume the major portion of the burden for child rearing, and women themselves feel an obligation to put family above their own needs, to the detriment of their own career development,” she said. “There still isn’t the sharing of responsibilities in two-career families to mitigate these problems.”

The paper includes a detailed ‘menu’ of proposed solutions. These include providing financial support to hire technicians for two to three years to carry on lab research while women researchers focus on child care at home, or otherwise supporting child care at home so women can continue their lab research.

The paper also proposes slowing down tenure clocks, delaying the tenure decision by two to three years to make up for lost time while women give birth and care for young children.

In addition to such programs, the list includes a category of solutions termed “cultural,” described as creating the cultural expectation that gender equity is a shared responsibility and incorporating those expectations into bonuses and merit raises of institutional leaders. Also included is the need to engage university and hospital boards of trustees to support gender equity.

Prof Curtis said that the paper aims to highlight the persistence of these gender differences persist and that global phenomena like the pandemic only worsen them.

“As much as we would like to think that gender differences in career development no longer exist, they do, and they adversely affect women more than men,” she said. “Understanding these issues and implementing solutions are the best ways to minimise potentially adverse effects on women’s careers.”

As the pandemic and its associated restrictions ease, Prof Curtis warned, “The situation is improving now that schools are open, but the next pandemic may only be a mutation away.”

Source: Buffalo University

Categories : GastrointestinalTags :

A Touch-sensing Protein Helps the Gut to ‘Feel’

On By ModernMedia
Anatomy of the gut
Source: Pixabay CC0

New research published in the journal Gastroenterology has discovered that a touch-sensing protein is present in the gut, with its presence likely playing a key role in constipation. The protein, called Piezo2, was found using both human gut samples and mice is not just in our fingers, but also in our gut.

“Many people suffer from digestive issues on a daily basis, such as chronic constipation, however we still don’t understand the cause which underlies most of them,” said Lauren Jones, lead author and final year PhD student.

“Our research identified Piezo2 in cells that line the human digestive tract, allowing them to sense physical stimuli, such as touch or pressure, that would occur when food is present. The cells then respond by releasing serotonin to stimulate gut contractions and push the food along.”

Last year, international researchers Ardem Patapoutian and David Julius were awarded the Nobel Prize in Physiology or Medicine for their research on receptors responsible for the perception of touch and temperature, including the discovery of Piezo2, now known to be responsible for sensing light touch on our skin.

Of potential clinical importance, the Flinders research team also discovered that the levels of Piezo2 decrease in the gut with age, and found that if the protein was removed only from gut serotonin cells, gut motility slowed down in mice, causing constipation.

The authors say this could be a potential contributing factor to age-related constipation and provide a possible path to treatment.

Researchers discover a nuclear import mechanism essential for organ growth and development

“Age-related constipation affects 1 in 2 adults over the age of 80, whilst constipation generally affects almost everyone at some point throughout their life,” says Ms Jones.

“It’s therefore extremely important we increase our understanding of the underlying mechanisms, so that we can find targeted solutions to improve the quality of life of the many people who suffer daily from various gut disorders, including constipation.

“This research provides the building blocks for both further research and the development of highly specific treatments to reduce the impacts of constipation.”

The authors say that, though more studies are needed to firmly link Piezo2 to constipation, the research overall is an important advancement into our understanding of gut physiology, opening up new targets for the treatment of digestive issues.

The insights allow for reduced side effects, explained Ms Jones: “More specifically, we now have the potential to create treatments that are taken orally and only directly impact these cells that line the gut, therefore significantly reducing side effects typically seen with many of the current medications.”

Source: News-Medical.Net

Categories : AgeingTags :

Cells in Mice Partially Reset to More Youthful States

On By ModernMedia
Mouse
Photo by Kanasi on Unsplash

Scientists have shown that they can safely and effectively reverse the epigenetic markers of age in middle-aged and elderly mice by partially resetting their cells to more youthful states – reducing many signs of ageing as they do so.

As organisms age, their cells have different epigenetic markers on their DNA compared to younger ones. It is known that adding a mixture of reprogramming molecules, also known as ‘Yamanaka factors’, to cells can reset these epigenetic marks to their original patterns. This approach enables researchers to turn back the clock for adult cells, developmentally speaking, into stem cells.

“We are elated that we can use this approach across the life span to slow down aging in normal animals. The technique is both safe and effective in mice,” said Juan Carlos Izpisua Belmonte, co-corresponding author, professor at the Salk Institute. “In addition to tackling age-related diseases, this approach may provide the biomedical community with a new tool to restore tissue and organismal health by improving cell function and resilience in different disease situations, such as neurodegenerative diseases.”

The Salk Institute research lab reported in 2016 that, for the first time, they were able use the Yamanaka factors to counter the signs of aging and increase life span in mice with a premature ageing disease. More recently, the lab found that the Yamanaka factors can accelerate muscle regeneration even in younger mice. Building on these studies, other scientists have used the same approach to improve the function of other tissues like the heart, brain and optic nerve.

In the new study, the researchers tested variations of the cellular rejuvenation approach in healthy animals as they aged. One group of mice received regular doses of the Yamanaka factors from the time they were 15 months old until 22 months, approximately equivalent to age 50 through 70 in humans. Another group was treated from 12 through 22 months, approximately age 35 to 70 in humans. And a third group was treated for just one month at age 25 months, similar to age 80 in humans.

“What we really wanted to establish was that using this approach for a longer time span is safe,” said Pradeep Reddy, study co-first author. “Indeed, we did not see any negative effects on the health, behaviour or body weight of these animals.”

No blood cell alterations or neurological changes were seen in the mice treated with the Yamanaka factors compared to control mice. Additionally, no cancers were observed in any of the groups of animals.

In terms of normal signs of ageing, the treated mice resembled younger animals in a number of ways. In both the kidneys and skin, the epigenetics of treated animals more closely resembled epigenetic patterns seen in younger animals. When injured, the skin cells of treated animals had a greater ability to proliferate and were less likely to form permanent scars, unlike normal older animals. Metabolic molecules also did not reflect normal age-related changes.

This youthfulness was observed in the animals treated for seven or 10 months with the Yamanaka factors, but not the animals treated for just one month. What’s more, when the treated animals were analysed midway through their treatment, the effects were not yet as evident. This suggests that the treatment is not simply pausing aging, but actively turning it backwards–- although more research is needed to differentiate between the two.

The team is now planning future research to analyse how specific molecules and genes are changed by long-term treatment with the Yamanaka factors. They are also developing new ways of delivering the factors.

“At the end of the day, we want to bring resilience and function back to older cells so that they are more resistant to stress, injury and disease,” said Reddy. “This study shows that, at least in mice, there’s a path forward to achieving that.”

The study was published in Nature Aging.

Source: Salk Institute