Monthly Archives: January 2021
Israel‘s Health Minister Edelstein provided ministry data showing that 2,272,000 people have so far had the first of the two-shot Pfizer-BioNTech vaccine, including 550,000 who have also had their second dose. The number represents close to a quarter of Israel’s 9.3 million citizens and maintains its position as the country with the highest per capita vaccination rate in the world, according to monitoring groups.
Edelstein on Wednesday presented figures showing that over 210,000 vaccination shots were administered the day before, a new record for the country’s mass inoculation program.
Israelis recieve a Covid-19 vaccine, at a vaccination center operated by the Tel Aviv Municipality
Urging continued adherence to Health Ministry lockdown guidelines, which on Tuesday were extended until January 31, Edelstein wrote “a little more and this will be behind us.”
His figures were more optimistic than numbers released by the ministry during the morning, which showed that 56,008 people had their first dose on Tuesday and another 114,769 had the second shot for a total of 170,777. It was not clear why there was a discrepancy in the numbers.
The ministry said 8,511 new cases were confirmed Tuesday, a drop of some 1,500 from the record-shattering 10,058 cases detected on Monday. The figure for Tuesday was the lowest weekday daily caseload in over a week. The positive test rate also dropped to 9.2%, having reached 10.2% on Monday.
Picture the familiar double helix of human DNA — a long, twisted ladder with 3 billion rungs on it, each made of a pair of genetic bases (A, T, C, and G). A mistake in just one base along that ladder — an A where there should be a G — can be enough to cause a disease. In fact, researchers have linked over 31,000 different mistakes, known as “point mutations,” to human diseases. Now, an advanced form of gene therapy — called base editing — could make it possible to safely correct them.
Base editing is a type of gene editing technology, just like CRISPR. However, while CRISPR cuts through both strands of the DNA ladder to swap in different genes, a base editor makes precise changes to individual letters along the genome — a much less invasive kind of DNA surgery.
“It’s like your spell-checker,” neuroscientist Jeffrey Holt said. “If you type the wrong letter, spell checker fixes it for you.” Base editing was first developed by Broad Institute researcher David Liu in 2016, and it’s not perfect — the best base editors still make off-target edits and aren’t 100% efficient. However, the technique is more efficient than CRISPR and causes fewer errors, which has made it the focus of considerable research into correcting disease-causing point mutations.
“Base editing is like your spell-checker. If you type the wrong letter, it fixes it for you,” explained Jeffrey Holt. Holt was part of a team that used base editing to partially restore the hearing of mice with a point mutation that causes deafness in people. Earlier in 2020, University of Illinois researchers used base editing to slow the progression of ALS in mice. More recently, Liu was part of a group that used base editing to correct the point mutation that causes progeria, a premature-aging syndrome, in mice. By changing a T to a C in a single gene, they were able to more than double the lifespan of mice with the disease.
There’s no guarantee that a therapy that works in mice will translate to humans (although gene editing is conceptually much simpler than drugs that rely on complex chemistry). To find out whether base editing can live up to its promise as a disease-curing technology, we need human studies — and now, one is just on the horizon.
On January 12, Massachusetts-based biotech company Verve Therapeutics announced the promising results of a study testing a base editing treatment for heterozygous familial hypercholesterolemia (HeFH), a genetic heart disease. HeFH is fairly common, affecting about one in 500 people, and it causes consistently high levels of “bad” cholesterol (LDL-C) — that makes people with the disease susceptible to heart attacks or strokes at a relatively young age. In primates with HeFH, Verve used base editing to change an A to a G in a single gene. Within two weeks, the animals’ blood LDL-C levels had dropped by 59%. Six months later, they were still just as low.The treatment, dubbed “VERVE-101,” was well-tolerated, with no adverse effects reported.
“When we started, we had no idea this would work,” Verve CEO Sekar Kathiresan said in a press release, adding, “It works, and we expect this to be durable for the lifetime of the animals.” Now, Verve wants to find out if VERVE-101 works in humans.
Norway expressed increasing concern about the safety of the Pfizer Inc. vaccine on elderly people with serious underlying health conditions after raising an estimate of the number who died after receiving inoculations to 29. The latest figure adds six to the number of known fatalities in Norway, and lowers the age group thought to be affected to 75 from 80. While it’s unclear exactly when the deaths occurred, Norway has given at least one dose to about 42,000 people and focused on those considered most at risk if they contract the virus, including the elderly.
“There are 13 deaths that have been assessed, and we are aware of another 16 deaths that are currently being assessed,” the agency said. All the reported deaths related to “elderly people with serious basic disorders,” it said. “Most people have experienced the expected side effects of the vaccine, such as nausea and vomiting, fever, local reactions at the injection site, and worsening of their underlying condition.”
Official reports of allergic reactions have been rare as governments rush to roll out vaccines to try to contain the global pandemic. U.S. authorities reported 21 cases of severe allergic reactions from Dec. 14-23 after administration of about 1.9 million initial doses of the Pfizer vaccine. The first Europe-wide safety report on the Pfizer-BioNTech vaccine is due to be published at the end of January. Until Friday, the vaccine produced by Pfizer and BioNTech SE was the only one available in Norway, and “all deaths are thus linked to this vaccine,” the Norwegian Medicines Agency said in a written response to Bloomberg on Saturday.
With the advance in nanotechnology, researchers across the globe have been exploring how to use nanoparticles for efficient drug delivery. Similar to nanoshells and nanovesicles, nanomicelles are extremely small structures and have been noted as an emerging platform in targeted therapy. Nanomicelles are globe-like structures with a hydrophilic outer shell and a hydrophobic interior. This dual property makes them a perfect carrier for delivering drug molecules.
Now a multi-disciplinary, multi-institutional team has created a nanomicelle that can be used to deliver a drug named docetaxel, which is commonly used to treat various cancers including breast, colon and lung cancer.
Modus operandi: Once injected intravenously, these nanomicelles can easily escape the circulation and enter the solid tumours.
“The ideal goal for cancer therapy is destroying the cancer cells without harming healthy cells of the body, and chemotherapeutics approved for treatment of cancer are highly toxic. The currently used docetaxel is a highly hydrophobic drug, and is dissolved in a chemical mixture (polysorbate-80 and alcohol). This aggravates its toxic effects on liver, blood cells, and lungs. So, there was an urgent and unmet need to develop effective drug delivery vehicles for docetaxel without these side effects,” explains Avinash Bajaj, from the Laboratory of Nanotechnology and Chemical Biology at the Regional Centre for Biotechnology, Faridabad. He is one of the corresponding authors of the paper recently published in Angewandte Chemie.
The nanomicelles are less than 100nm in size and are stable at room temperature. Once injected intravenously these nanomicelles can easily escape the circulation and enter the solid tumours where the blood vessels are found to be leaky. These leaky blood vessels are absent in the healthy organs. “Chemical conjugation would render the phospholipid-docetaxel prodrug to be silent in the circulation and healthy organs. But once it enters the cancer cells, the enzymes will cleave the bond to activate the drug, and kill the cancer cells,” adds Dr. Bajaj.
The team tested the effectiveness of the nanomicelles in a mice breast tumour model and was found to help in tumour regression. Its toxicity was compared with the currently used FDA approved formulation and found to be less toxic. Similar promising results were seen when tested in higher model organisms including rats, rabbits and rhesus monkeys.
Patients across the UK who are admitted to intensive care units due to COVID-19 are set to receive new life-saving treatments which can reduce the time spent in hospital by up to 10 days, the government has announced today (Thursday 7 January).
Results from the government-funded REMAP-CAP clinical trial published today showed tocilizumab and sarilumab reduced the relative risk of death by 24%, when administered to patients within 24 hours of entering intensive care.
Most of the data came from when the drugs were administered in addition to a corticosteroid, such as dexamethasone – also discovered through government-backed research through the RECOVERY clinical trial – which is already provided as standard of care to the NHS.
Patients receiving these drugs, typically used to treat rheumatoid arthritis, left intensive care between 7 to 10 days earlier on average. The rollout of these treatments could therefore contribute significantly towards reducing pressures on hospitals over the coming weeks and months.
Under a winter’s snow cover on the outskirts of Quebec City in Canada, a high-tech greenhouse, set at a balmy 23 C, is growing row after row of a weed that could help end the coronavirus pandemic. It’s called Nicotiana benthamiana, a relative of the tobacco plant, native to Australia, and it is a key to biopharmaceutical company Medicago’s COVID-19 vaccine. Medicago is the leading Canadian-based contender to produce a vaccine, with an agreement to provide the federal government with 76 million doses if approved for use.
Medicago’s vaulting onto the mainstage could provide a breakthrough for vaccine science. It involves a new technology that’s rapid and nimble, and a vaccine that can be stored at normal fridge temperatures, of 2 C to 8 C, unlike the two other vaccines currently in circulation, which each require frozen or ultra-cold frozen storage. While it’s possible the company may emerge as the new wunderkind of the Canadian biotech sector, it wasn’t without adversity. For years, Medicago warned that Canada needed to prepare itself for a pandemic and lobbied government officials for funding to build a domestic manufacturing site for a vaccine. But Medicago didn’t get what it needed from the federal government until after the COVID-19 crisis struck. On top of that, in the middle of a pandemic, Medicago is restructuring. In July, it announced plans to distance itself from a significant shareholder, Philip Morris International, which owns about one-third of the company — a controversial association with Big Tobacco that has been the source of roadblocks and criticism. Then in December, the company replaced its president and CEO. But despite this, Medicago hasn’t lost sight of its goal: a vaccine.
In phase one of its clinical trials, 100 per cent of people who received its COVID-19 vaccine developed significant antibody responses with no severe adverse effects. Phase two clinical trials are currently wrapping up and phase three is expected to begin later this month. It will involve 30,000 people in 11 countries — including Canada — and will ultimately determine if the vaccine protects people from COVID-19. The vaccine requires two doses, 21 days apart, and if approved by Health Canada, could be in the arms of Canadians by the second half of this year.
Alzheimer’s Disease (AD) is probably more diverse than our traditional models suggest. Postmortem, RNA sequencing has revealed three major molecular subtypes of the disease, each of which presents differently in the brain and which holds a unique genetic risk. Such knowledge could help us predict who is most vulnerable to each subtype, how their disease might progress and what treatments might suit them best, potentially leading to better outcomes. It could also help explain why effective treatments for AD have proved so challenging to find thus far.
“The mouse models we currently have for pharmaceutical research match a particular subset of AD, but not all subtypes simultaneously. This may partially explain why a vast majority of drugs that succeeded in specific mouse models do not align with generalised human trials across all AD subtypes,” say the authors. “Therefore,” the authors conclude, “subtyping patients with AD is a critical step toward precision medicine for this devastating disease.”
Traditionally, AD is thought to be marked by clumps of amyloid-beta plaques (Aβ), as well as tangles of tau proteins (NFTs) found in postmortem biopsies of the brain. Both of these markers have become synonymous with the disease, but in recent years our leading hypotheses about what they actually do to our brains have come under question. Typically, accumulations of Aβ and NFT are thought to drive neuronal and synaptic loss, predominantly within the cerebral cortex and hippocampus. Further degeneration then follows, including inflammation and degeneration of nerve cells‘ protective coating, which causes signals in our brains to slow down.
Strangely enough, however, recent evidence has shown up to a third of patients with a confirmed, clinical diagnosis have no Aβ plaques in postmortem biopsies. What’s more, many of those found with plaques at death did not show cognitive impairment in life. Instead of being an early trigger of AD, setting off neurodegeneration and driving memory loss and confusion, in some people, Aβ plaques appear to be latecomers. On the other hand, recent evidence suggests tau proteins are there from the very earliest stages.
In light of all this research, it’s highly likely there are specific subtypes of AD that we simply haven’t teased apart yet. The new research has helped unbraid three major strands. To do this, researchers analysed 1,543 transcriptomes – the genetic processes being express in the cell – across five brain regions, which were collected post mortem from two AD cohorts.