Harvesting baker's yeast for aging-related therapeutics

 Around the world, more people are growing older. According to the World Health Organisation, 1 in 6 people in the world will be aged 60 years or over by 2030. By 2050, the world's population of people aged 60 years and older will double to 2.1 billion. The number of persons aged 80 years or older is expected to triple between 2020 and 2050 to reach 426 million.

In line with the growing number of seniors, the number of people living with age-related diseases such as dementia, including Alzheimer's Disease and Parkinson's Disease is also expected to increase exponentially. These age-related diseases are an emerging impediment to healthy and functional aging.

A class of medicine used in the treatment of neuro-cognitive diseases and other neurological ailments (migraines, headaches, etc) are currently obtained from extracts of the ergot fungus. However, continued cultivation of the ergot fungus for medicine is not sustainable as industrial agriculture is one of the largest contributors to carbon emissions worldwide.

To meet the global demand for such medication, between 10-15 tons of D-lysergic acid (DLA), an ingredient used in producing the medicine, are produced each year. The ergot fungi are parasites to cereal crops such as rye, and their cultivation entails growing them on top of fields of such crops that could otherwise be used for food production. In order to reduce the use of arable land to produce such medicine, a group of researchers from the Yong Loo Lin School of Medicine at the National University of Singapore (NUS Medicine) and Imperial College London have trialled an alternative way of producing DLA.

Using yeast commonly known to make bread, and synthetic biology techniques, the team introduced the enzymes from the ergot fungus into baker's yeast, which also happens to be another fungus. Through a process known as fermentation, the modified yeast was then grown using sugar to produce DLA. Natural fermentation has been used throughout human history for food production, most notably in the production of bread and beer. Just like how baker's yeast has been used to produce the alcohol and flavours in beer, fermentation using the modified yeast can now produce DLA.

The study was published in Nature Communications on 7 Feb 2022.

"It is possible to produce up to five tons of DLA annually using the current yeast strain; and with further optimisation, commercial production levels could be attainable," explained Associate Professor Yew Wen Shan from the Department of Biochemistry at NUS Medicine and the co-lead Principal Investigator of the study. "This research builds upon the growing body of work that use microbes such as yeast for the sustainable production of medicine and functional food ingredients."

Professor Paul Freemont, from the Department of Infectious Disease at Imperial College London, said: "Yeast has been a key part of human civilization for thousands of years, helping us to make bread and brew beer. But our relationship with this familiar microbe is evolving. Through this exciting collaboration we have been able to harness fungal cells to act as miniature factories to produce raw compounds for medicines. This is an example of how something seemingly small and inconsequential has the potential to change human lives, providing the drugs which will enable us to age better and reduce the environmental impact of industrial drug production."

Story Source:

Materials provided by National University of Singapore, Yong Loo Lin School of Medicine. Note: Content may be edited for style and length.

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Journal Reference:

1. Garrett Wong, Li Rong Lim, Yong Quan Tan, Maybelle Kho Go, David J. Bell, Paul S. Freemont, Wen Shan Yew. Reconstituting the complete biosynthesis of D-lysergic acid in yeast. Nature Communications, 2022; 13 (1) DOI: 10.1038/s41467-022-28386-6

https://www.sciencedaily.com/releases/2022/02/220210154135.htm

CDC Cuts Booster Interval for the Immunocompromised

 The CDC updated its interim guidance on COVID-19 vaccination to give immunocompromised people a shorter wait for their booster shot.

It is now recommended that people who are moderately or severely immunocompromised receive a booster 3 months -- down from 5 months previously -- after the third dose of an mRNA vaccine, for a total of four doses. Previewed at last week's meeting of the Advisory Committee on Immunization Practices (ACIP), this change was attributed to concern about the immune response and loss of mRNA protection over time for these patients.

Immunocompromised people who receive Johnson & Johnson's COVID-19 vaccine are advised to receive an mRNA vaccine dose at least 4 weeks later and a booster dose at least 2 months after that, for a total of three doses (mRNA preferred for the booster as well).

Unchanged is the COVID-19 vaccination schedule for the general population. An 8-week interval between the first and second doses of Pfizer and Moderna's vaccine was discussed at length at the ACIP meeting.

In addition, CDC's new guidelines provide more clarity for COVID-19 vaccination for people who receive doses abroad:

• People who received FDA-approved or -authorized vaccines may complete their primary series and get boosted according to the regular schedule
• Those who got a World Health Organization (WHO)-listed, but not FDA-authorized/approved vaccine, are recommended to switch to an mRNA vaccine when it is time to complete their primary series or get boosted
• People who got COVID vaccines not meeting FDA or WHO criteria do not count as being vaccinated in the U.S.; they should start their primary series at least 28 days after the last dose of the unauthorized vaccine

As for vaccination after COVID-19 treatment or post-exposure prophylaxis, it is no longer necessary to delay vaccine doses for people getting monoclonal antibodies or convalescent plasma. "The balance of benefits vs risks favors proceeding with vaccination even considering the possibility of diminished vaccine effectiveness in this situation," according to the CDC's interim guidance.

The latest recommendations also strengthen the warning that people who develop myocarditis or pericarditis after mRNA COVID-19 vaccination "should not" get a subsequent dose of any COVID-19 vaccine -- though adult men choosing to do so may consider the Johnson & Johnson vaccine.

https://www.medpagetoday.com/infectiousdisease/covid19vaccine/97168

China says not granting passport renewals for non-essential travel

 China’s National Immigration Administration said it will not be renewing passports for non-essential travel while the international COVID-19 epidemic situation is still severe and cross border travel poses “great security risks”.

The administration said in a statement on social media it will “normally issue passports” for individuals who need to travel abroad for study, employment, or business.

But rumours it will issue passport renewals for individuals looking to travel abroad for leisure are false, the authority said.

China has tightened controls over its citizens’ cross-border travel to lower the risk of the virus being brought in from overseas and spreading domestically.

It has suspended the issuance of new common passports for individuals who intend to go abroad for non-urgent matters.

https://www.metro.us/china-says-not-granting/

Key bridge to U.S. remains closed as Canada police clear protesters

 Canadian police cleared protesters and vehicles that had blocked a vital trade route on the border with the United States, making some arrests, but the bridge was not yet open to traffic on Sunday.

The officers moved in after a tense standoff between Canadian police and demonstrators since Friday when a court order and threats of arrest failed to end the blockade of the Ambassador Bridge in Windsor, Ontario, which entered its sixth day on Sunday.

“Enforcement actions continue at the demonstration area with arrests being made. Vehicles being towed. Please continue avoiding the area,” Windsor Police said in a Twitter post early on Sunday, without saying how many had been arrested.

Police stepped up their presence with more than 50 vehicles, including cruisers, buses and an armoured car on Sunday, as the number of protesters dropped to around 45 from roughly 100 on Saturday.

Windsor Police tweeted “there will be zero tolerance for illegal activity”.

U.S. President Joe Biden has asked Canadian Prime Minister Justin Trudeau to use federal powers to end the blockade https://www.reuters.com/world/americas/truckers-ambassador-bridge-perfect-spot-threaten-us-canada-trade-2022-02-11 of the bridge, North America’s busiest land border crossing. Since Monday, protesters in trucks, cars and vans have blocked traffic in both directions, choking the supply chain for Detroit’s carmakers.

Police moved in early on Saturday, pushing protesters back from the foot of the bridge, but more people streamed into the area in the afternoon and the operation appeared to have stalled.

“I am very hopeful still that police can … try and get to these folks in a reasonable way and have them understand that it’s time to move on,” Windsor Mayor Drew Dilkens told CBC News. “We can no longer afford as a country to keep it closed.”

The bridge carries about $360 million a day in two-way cargoes – 25% of the value of all U.S.-Canada goods trade.

The “Freedom Convoy” protests, started in the national capital Ottawa by Canadian truckers opposing a vaccinate-or-quarantine mandate for cross-border drivers, entered its 17th day on Sunday. But it has now morphed into a rallying point against broader COVID-19 curbs, carbon tax and other issues, with people joining in cars, pick-up trucks and farm vehicles.

Protests erupted across several cities in Canada on Saturday, with some 4,000 people in downtown Ottawa. Financial capital Toronto had some 1,000 demonstrators, though the police had shut key access roads to the central business district.

In the west, hundreds of protesters choked intersections along the Pacific Highway with vehicles leading to the Canada-U.S. border crossing in South Surrey, British Columbia. Several, camped out near the border crossing, vowed to stay “as long as is needed” until all COVID-19 restrictions are lifted.

Strangling bilateral trade, protests have spread to three border points, including in Alberta and Manitoba.

Canadian police have said the protests have been partly funded by U.S. supporters, and Ontario froze funds donated via one U.S. platform GiveSendGo on Thursday.

Ford Motor Co, the second-largest U.S. automaker, General Motors Co and Toyota Motor Corp all have announced production cuts. Companies have diverted cargo to stem losses during the cuts.

The estimated loss so far from the blockades to the auto industry alone could be as high as $850 million, based on IHS Markit’s data, which puts the 2021 daily flow in vehicles and parts at $141.1 million a day.

“This is the busiest border crossing, so it’s not just automotive,” Mayor Dilkens said. “We are talking about things that impact the entire nation here. That’s why finding a resolution is so important.”

https://www.metro.us/key-bridge-to-u-s/

38 Lawmakers Demand Biden Undergo Cognitive Testing As Soon As Possible

 In a letter, signed by 37 of his Republican colleagues in Congress, Texas Rep. Dr. Ronny Jackson warns that President Biden's "mental decline and forgetfulness have become more apparent over the past two years," and urges the 79-year-old to take a cognitive aptitude test (just as former President Trump did).

“My colleagues and I are again asking President Biden to immediately undergo a formal cognitive screening exam, such as the Montreal Cognitive Assessment,” Jackson said.

“As a former physician to three Presidents of the United States, I know what it takes mentally and physically to execute the duties of Commander-in-Chief and Head of State,” said Jackson, who served as a White House doctor to former Presidents George W. Bush, Barack Obama and Donald Trump.

Jackson may have a point given this recent appearance...

“Joe Biden has continually proven to me and to the world that something isn’t right. The American people deserve to have absolute confidence in their president’s cognitive ability,” he said.

He is not alone in his concerns as a recent Politico poll found that 48% of Americans think the president is not "mentally fit" to do the job.

It's not just 'white supremacists' that are worried about the president's cognitive abilities, even Australia's mainstream media is picking up on it...

Dr. Jackson appeared on Fox News' 'Hannity' to explain his concerns

Read the full letter below...

https://www.zerohedge.com/political/something-isnt-right-38-lawmakers-demand-biden-undergo-cognitive-testing-soon-possible

Dexcom bests its ‘best year ever’ with 27% surge to $2.5B revenue in 2021

 How does a medtech company top its “best year ever”? According to Dexcom, by adding another half-billion dollars in revenue, growing the customer base by upwards of 30% and collecting a handful of regulatory clearances for new product launches.

The continuous glucose monitor maker reported those and several other wins this week in its year-end financial report. For all of 2021, it tallied up $2.45 billion in revenue, up 27% from its $1.9 billion total in 2020, a year that CEO Kevin Sayer had previously described as the company’s best ever.

The company’s 2021 earnings also top its own forecasts for the year. While wrapping up 2020, Dexcom offered a prediction that the next year’s revenues would fall between $2.21 billion and $2.31 billion, representing year-over-year growth of up to 20%. It upped those expectations toward the end of the year, suggesting in its third-quarter earnings report that the full year’s revenue would inch closer to the $2.425 billion to $2.45 billion range—a range that it ultimately maxed out.

Those rising revenues were helped along by another record-setting year of growth in Dexcom’s patient pool. Patient volumes both in and outside of the U.S. clocked in at the high end of the 30% to 40% range, CFO Jereme Sylvain said during a call with investors on Thursday.

Perhaps Dexcom’s most important achievement of 2021, according to Sayer, was the publication of data demonstrating the effectiveness of its G7 CGM sensor. The system was shown to produce blood sugar readings with a mean average relative difference of just about 8% compared to those of standard glucose meters.

The G7 device is about 60% smaller than the preceding G6 model and is designed for use by patients with either Type 1 or Type 2 diabetes to track their glucose levels.

“We set out in 2021 with a few key goals in mind: to complete the clinical and regulatory process for G7 and prepare for significant launches, to validate health and economic outcomes for Dexcom CGM beyond the intent of insulin using population, to broaden access to Dexcom CGM globally through evidence, advocacy and leveraging our growing scale and efficiency, and to strengthen our product portfolio for future growth through differentiated software capabilities,” Sayer said during Thursday’s call.

“Our progress on all these initiatives contributed to a great 2021 and have us looking forward to a big year ahead in 2022,” Sayer added.

Once again, the G7 sensor will be at the top of Dexcom’s priorities for the upcoming year. It submitted regulatory applications in both the U.S. and Europe at the end of 2021 and is already expecting the E.U.’s CE mark clearance to come through any day now.

“We’re down to the last steps for CE mark—literally, procedural-type discussions with documentation that will take place in the near term,” Sayer said on the call. “We’re very confident that we’ll get the CE mark very soon, and then we will start our limited launch in Europe and then roll out to the full launch after that.”

Meanwhile, he said, Dexcom has had “initial dialogue” with the FDA about the submission and isn’t expecting any delays in the stateside regulatory process, helped along by the “great clinical data” it was able to include in the submission.

Overall, if things go according to schedule with the regulatory agencies and the rollout of the G7 sensor, Dexcom is forecasting another bump of up to 20% in its full-year 2022 revenue, bringing the total up somewhere between $2.82 billion and $2.94 billion.

https://www.fiercebiotech.com/medtech/dexcom-bests-its-best-year-ever-27-surge-to-2-5b-revenue-2021

Illumina CEO: Why speeding Grail's cancer test to patients requires 'every part of our company'

 At several points over the past few months, as Illumina has moved forward with its $8 billion acquisition of the cancer blood test maker Grail despite the deal falling under the regulatory microscope, Francis deSouza, CEO of the DNA sequencing giant, has said that a full integration of the two companies is the only path forward.

Without it, deSouza has said, Grail’s multi-cancer early detection test will take much longer to reach physicians and clinics the world over, ultimately resulting in more lives lost to the disease.

“The European regulatory and reimbursement environment is complex,” with layers of approvals necessary from continental, national and in some places regional authorities, deSouza said in an interview.

“That is a lot of work, and we have a lot of people on the ground doing that. That is not something that we could just do as a favor or as a consulting assignment to Grail—that will take a lot of people working in our company,” he added.

Currently, Grail’s prescription-only test is available in the U.S. after a highly anticipated launch last year, but it does not yet enjoy broad insurance coverage; it carries an out-of-pocket price of $950 per screening that aims to detect the signs of as many as 50 different types of cancer. But in the future, Illumina plans to throw its considerable weight behind the test to help drive up its adoption.

“We have production labs that do millions of genomic tests a year in the U.S. and outside—they’re our labs, with our people and our other tests, and that’s not something we could rent to somebody else to just roll their test in our environment,” deSouza said.

“It really touches every part of our company to get the benefits of accelerating Grail,” he added. “We've lowered the cost of sequencing by over 99% since 2007…we couldn’t just send in our engineers to optimize their product. Those are the kinds of things that we could really only do if they’re fully part of the loop.”

So far, Grail has logged about $12 million in revenue during 2021—a small drop compared to the $931 million it racked up in year-long expenses. Part of the company’s revenues also came from research partnerships as Grail works to develop a second blood test for tracking minimal residual disease and monitoring patients for cancer recurrence. 

In 2022, Illumina expects Grail’s income to begin rising dramatically as Galleri sees wider use, to between $70 million and $90 million.

Illumina’s earnings report included its consolidated numbers as well as a section just for Grail, which it’s been holding at arm’s length since completing its acquisition last August despite an ongoing antitrust investigation by the European Commission. 

Until the regulators in Brussels come to a final decision—which deSouza now expects in the second quarter of this year, rather than at the end of March—Ilumina is required to hold onto Grail as a distinct and separately operated company.

For Illumina more broadly, and despite record revenue and continued demand for its DNA sequencers and consumables, the company’s net income for 2021’s fourth quarter dropped to $112 million—down 56% compared to the same period the year before—thanks to bigger spends on R&D and administrative expenses.

Still, the company’s $1.2 billion in total sales reached a new quarterly high, representing a 26% gain over revenues raised during the last three months of 2020. For the full year, Illumina brought in more than $4.5 billion, amounting to a 40% increase compared to the prior fiscal year.

That translated into $762 million in annual net income—more than the $656 million logged during the first year of the COVID-19 pandemic, but a bit less than the $990 million Illumina saw in 2019.

Illumina spent $350 million on R&D last quarter, $150 million more than the year before, and $1.1 billion for the year, totaling about 26% of the company’s annual revenue. Selling, general and administrative expenses, meanwhile, totaled $426 million for the quarter and about $2.1 billion for the year.

“We believe there is still a lot of innovation needed to open up this market and make genomics as widely accessible as we think it will need to be—because we believe it's ultimately going to be a key component of our healthcare system,” deSouza said.

“We need to continue to drive the prices down. We need to make the end-to-end system simpler to use. We need to have more cleared products on the market,” he said. “And we need to add not just genomics, but transcriptomics and proteomics, and have a multi-omic view of an individual. So all of that is what drives our R&D spend.”

That includes the development of Infinity, an improvement upon the company’s library prep system, which aims to unlock longer reads of DNA through its currently installed base of short-read instruments. 

By offering strings of up to 10 kilobase pairs in length from the same machine, Illumina aims to compete with the developers of more specialized, long-read hardware—such as Pacific Biosciences and Oxford Nanopore—while researchers’ requests of DNA sequencing technologies continue to become more complex.

Illumina announced Infinity in January during the J.P. Morgan Healthcare Conference, alongside a new project dubbed Chemistry X, described as a ground-up redevelopment of the company’s reagents, dyes and polymerases. Chemistry X will serve as the main platform for new machines going forward, and Illumina has already begun setting up a new large-scale manufacturing facility.

During 2021, the company shipped more than 3,200 genetic sequencers and added more than 930 new customers—an increase of more than half compared to 2020 or 2019—with Illumina’s total installed base of machines passing 20,000 as a result.

And by the end of last year, Illumina’s backlog of orders for instruments and consumables had doubled compared to the start of the year—growth that Chief Financial Officer Sam Samad attributed to organic demand, rather than troubles in the international supply chain.

“We’ve taken a lot of steps to ensure the integrity of the supply chain, and that we can provide products to customers,” Samad said on a call with investors. “We’ve increased the amount of distribution center capacity we have, we’ve increased our safety stocks of consumables…we have not really seen disruptions.”

For 2022, Illumina expects to see its revenues grow 14% to 16%—to between $5.16 billion and $5.25 billion—driven in part by 10% year-over-year gains in the number of placements of its analyzers.

And while last year the company saw $220 million in revenues from international COVID-19 surveillance work—including sequencing the virus’ genome to spot emerging variants and mutations—Illumina anticipates those efforts will slow over 2022, with sales dropping to between $130 million and $150 million.

https://www.fiercebiotech.com/medtech/illumina-posts-record-revenues-as-ceo-desouza-pitches-path-forward-for-grail