Tag: 5/2/21

Categories : Genetics New Compounds and TreatmentsTags :

Embracing Ethnic Genetic Diversity in Drug Design

On By ModernMedia

Although human beings have a great deal of genetic similarity, small genetic differences can nonetheless lead to very different results in drug effects.

Pharmacologist Namandje Bumpus, PhD—who recently became the first African American woman to head a Johns Hopkins University School of Medicine department, and is the only African American woman leading a pharmacology department in the country—explains why certain drugs can have different effects between distinct populations. Warfarin, for example, is known to be less effective in people of African descent.  

As new vaccines and treatments are developed to fight the COVID pandemic, which have disproportionately affected certain ethnic groups. According to APM Research Lab, in the US as of 2 Feb, Pacific Islanders are 2.7 times as likely to die from COVID as whites (adjusted for age), compared to 0.9 times for Asian Americans.

In light of these differences, Bumpus laid out a four-part plan to improve the equity of drug development.

Merely increasing the representation of races in drug trials is insufficient. Her plan includes: laboratory research to study genetic variability; diversifying the scientific workforce; diversity requirements for funding agencies; and diversity reporting requirements on clinical trial demographics in published articles.

Bumpus said that with genetic technology, animals can be engineered to “bolster predictability of drug outcomes and provide a mechanistic foundation for understanding disparities.”

Genetic variations linked to drug response are often associated with a family of enzymes, cytochromes P450. In humans this enzyme family processes about 75% of clinically available drugs. Subtle genetic differences can however lead to altered enzymes in humans, and these are more common in certain ethnic groups. 

This framework, Bumpus said, could compel the drug development field to move toward a future where “treatments are most likely to work for all people” and “existing health disparities are not further exacerbated.”

Source: Medical Xpress

Journal information: Namandjé N. Bumpus, “For better drugs, diversify clinical trials,” Science  05 Feb 2021: Vol. 371, Issue 6529, pp. 570-571. DOI: 10.1126/science.abe2565

Categories : Diseases, Syndromes and Conditions Hospitals PaediatricsTags :

Children with Sepsis Respond Better to ‘Relaxed’ Care Bundle

On By ModernMedia

Following a ‘relaxed care bundle’ was linked to lower 30-day mortality and shorter hospital stays among children with sepsis, according to preliminary data from the Improving Pediatric Sepsis Outcomes (IPSO) FACTO trial.

The study findings were presented virtually at the Society of Critical Care Medicine’s Critical Care Congress.

Sepsis is the leading cause of death in children, with an estimated 7.5 million deaths a year. Childhood sepsis includes severe pneumonia, severe diarrhoea, severe malaria, and severe measles. Some 25-40% of children who recover from sepsis still have long-term consequences.

The ‘relaxed’ sepsis bundle is based on a group of best evidence-based interventions. It involves an initial fluid bolus delivery within 60 minutes, as opposed to 20 minutes; and antibiotic delivery within 180 instead of 60 minutes. Accepted sepsis recognition protocols (screen, huddle, or care order) were also involved with the bundle.

This trial data came from about 40 000 patients with sepsis or suspected sepsis at a range of children’s hospitals across the US, from 2017 to 2019. Raina M Paul, MD, of Advocate Children’s Hospital, Illinois, USA reported the data, saying that the relaxed bundle saw better outcomes than the more original bundle which was more time-restrictive. 
Sepsis-attributable mortality fell by 48.9% among the relaxed bolus-compliant versus non-compliant group (3.1% vs 3.5%), and by 13.7% in original bundle-compliant vs non-compliant cases. Following all aspects of the relaxed bundle was associated with a reduction in median days in hospital from 9 to 6 days.

In a separate presentation, Kayla Bronder Phelps, MD, of CS Mott Children’s Hospital in Michigan, USA, reported the results of a study that showed children hospitalised for severe sepsis were likely to have longer hospital stays if they were from lower-income neighbourhoods. Using a national database, she identified 10 130 cases of children with severe sepsis. Severe sepsis hospitalisations were also highest among the lowest-income quartile, reflecting the fact that there were more children living in low-income neighbourhoods.

Overall, 8.4% of children in the cohort died of sepsis during hospitalisation, with no association between mortality rates and income level. However, children in the lowest-income areas spent a median 9 days in the hospital, while children from the highest-income areas spent 8 days.

Bronder Phelps noted that the study is among the first to examine the impact of poverty on paediatric sepsis outcomes. Poverty is a known risk factor for a wide range of paediatric diseases, such as neonatal bacterial infection, asthma, and migraine, and in adults, poverty is associated with poorer outcomes including higher mortality rates.

Source: MedPage Today

Presentation information 1: Paul R, et al “Improving pediatric sepsis outcomes for all children together (IPSO FACTO): Interim results” SCCM 2021; Abstract 32.

Presentation information 2: Phelps K, et al “The association of socioeconomic status and pediatric sepsis outcomes” SCCM 2021; Abstract 37.

Categories : AgeingTags :

APLS1 Inhibitors Eliminate Senescent Cells to Ameliorate Ageing

On By ModernMedia

A new technique has been developed to eliminate senescent cells that are involved in many age-related diseases, according to a study by researchers at the University of Tokyo.

As ageing progresses, cancers emerge, motor function declines through muscle loss, and metabolic disorders occur due to adipose tissue atrophy. Senescent cells accumulating in organs are behind many of these problems; their telomeres having shortened through divisions as a result of multiple stresses and now at their replication limit, they now no longer function effectively. Previous research using genetic engineering to knock out senescent cells in mice was able to put the onset of age-related diseases such as arteriosclerosis and renal damage, and extended life expectancy. However, the research did not yield a drug which could be given as a treatment.

To tackle this problem, the researchers created a way to produce large numbers of purified senescent. cells to search for genetic targets for drugs. One of the ways they found involved GLS1, a gene involved in glutamine. On testing with GLS1 inhibitors, senescent cells were vulnerable due to damage to the lysosomal membrane and lower intracellular pH. Lysosomes are organelles which produce enzymes to destroy defunct cell parts, bacteria and viruses if needed, and the cell itself if apoptosis is triggered. They also have an essential role in the regulation of intracellular pH, and are very acidic, having to be protected from the rest of the cell by a membrane. Analysing the dynamics of lysosomes, the team found that damage to the lysosomal membranes in senescent cells decreases intracellular pH.

When they administered GLS1 inhibitors to old mice, knocking out senescent cells, their ageing was significantly improved. The symptoms of obese diabetes, arteriosclerosis, and fatty liver disease were ameliorated. GLS1 inhibitors are already being used in trials as cancer treatments.
“We hope that innovative anti-aging therapies and treatments for geriatric diseases will be developed that can remove senescent cells by treatment with GLS1 inhibitors,” said Professor Nakanishi.

Source: News-Medical.Net

Journal information: Johmura, Y., et al. (2021) Senolysis by glutaminolysis inhibition ameliorates various age-associated disorders. Science. doi.org/10.1126/science.abb5916.

Categories : COVID General InterestTags :

Drone Company to Start New Rural Vaccine Delivery Service

On By ModernMedia

Zipline, a company that has made its name using drones to deliver medicines to remote locations in countries like Rwanda, has announced that it is to expand its capability to include all COVID vaccines.

In a press release, Zipline said that it is partnering with a COVID vaccine manufacturer, the identity of which was not disclosed, to add on the ability to deliver vaccines that require ultra cold temperatures in specialised refrigerated containers.

For remote rural locations, the Pfizer/BioNTech vaccine is not an option because of  its stringent temperature storage requirements of minus 70 degrees celsius. In such situations, the choice of COVID vaccines is limited to the more expensive Moderna vaccine, which still requires freezing temperatures, or vaccines like those from Johnsons & Johnson or AstraZeneca, which don’t have as high effectiveness but are able to be stored at normal refrigerator temperature ranges.

Zipline is planning to add these ultracold storage refrigerators at all of its drone bases. A clinic in its network would be able to request a few dozen doses of vaccine, and the company’s drones would be able to deliver it in a special refrigerated container.

Zipline operates fixed-wing, battery-powered drones that can make a round trip of up to 80 kilometres. Each base that the drones operate from can service an area of over 22 500 square kilometres, completely ignoring difficult terrain and lack of road access which may endanger drivers. A trip which could take hours in a 4 by 4 can be done in under an hour.
The drones can deliver a 1.75kg payload by parachute at a designated location, and return to base. Since the drone navigates by GPS, it can do so in a range of weather conditions, and by day or night.

Zipline CEO Keller Rinaudo said that his company wants to help rural areas that have been hard hit by COVID. “Where you live shouldn’t determine whether or not you get a COVID-19 vaccine,” he said in the release. “We can help health systems bypass infrastructure and supply chain challenges through instant delivery.”

Source: Bloomberg

Categories : COVIDTags :

UK to Look at Mixing of Different Vaccines

On By ModernMedia

The UK is launching a trial to explore the mixing of vaccines can be combined. Some, like Russia’s Sputnik vaccine, already combine two different types of vaccines, but these were specifically designed and tested to work together. 

Current guidance in the UK says that anyone who receives a Pfizer-BioNTech or Oxford-AstraZeneca vaccine dose should get the second dose of that same vaccine. Only in exceptional circumstances such as not knowing what vaccine was given will a different vaccine be administered.

The main aim was to enhance logistical flexibility. The Oxford/AstraZeneca, Johnson & Johnson and Novavax vaccines can all be stored at normal refrigerator temperatures, while the Moderna vaccine must be stored at -20C, within normal freezer range, and Pfizer/BioNTech’s vaccine needs an ultra-cold -70C. Not requiring a second dose of the same vaccine could ease up storage requirements. 

However, with previous vaccines, mixing different vaccine types worked and even strengthened their overall effectiveness. Some Ebola immunisation programmes, for example, combine two different vaccines to achieve greater protection.

The trial will comprise some 800 participants aged 50 or older, receiving a combination of Oxford/AstraZeneca and Pfizer/BioNTech in either order.

Some vaccines that work by using a virus to deliver the antigens, and there is some evidence to suggest that the immune system starts to focus on the viral delivery system instead of the antigen. Thus, combining vaccines will keep the immune system’s attention on the antigens.

Chief investigator, Prof Matthew Snape from the University of Oxford, said the “tremendously exciting study” would provide critical information for vaccine rollouts.

Animal studies have shown “a better antibody response with a mixed schedule rather than the straight schedule” of vaccine doses, he said.

“It will be really interesting to see if the different delivery methods actually could lead to an enhanced immune response [in humans],” he said, “or at least a response that’s as good as giving the straight schedule of the same doses”.

Source: BBC News

Categories : Cancer GeneticsTags :

RNA Knockout Halts the Spread of Triple-negative Breast Cancer

On By ModernMedia

The University of Westminster has released a new study showing that taking out small chunks of human DNA called microRNA can reverse the spread of triple negative breast cancer cells.

The study also suggested that microRNAs could be targeted to spot and treat triple negative breast cancer. Breast cancer is the most common cancer in women, and triple negative breast cancer makes up 10-20% of cases.

MicroRNAs (miRs) have important roles in cellular functioning and signalling, and are heavily involved in the growth and metastasis of cancers. The researchers found that miR-21, a major breast cancer-related RNA, is increased in triple negative breast cancer and is also associated with metastasis.

Using CRISPR/Cas9, the researchers knocked out miR-21 from the cancer cells, and discovered that the cancer cells’ metastatic properties were reversed. They also observed that they released smaller vesicles, which release lipid blobs that play an important part in cancer spread. There was also less miR-21 carried in the vesicles, which also carry disease-related molecules to other cells.

Lead researcher Dr Pinar Uysal-Onganer of the University of Westminster, said: “This is an important study which contributes to better understanding of roles of miRs in aggressive cancer types such as triple negative breast cancer. We are now aiming to clarify the relationships between miR-21 and cancer drug resistance, which is another important factor that limits cancer cure.”

Source: Medical Xpress

Journal information: Elif Damla Arisan et al. MiR-21 is Required for the Epithelial–Mesenchymal Transition in MDA-MB-231 Breast Cancer Cells, International Journal of Molecular Sciences (2021). DOI: 10.3390/ijms22041557