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Unlocking how to use mRNA to target Alzheimer’s disease

Scientists at The Florey have developed an mRNA technology approach to target the toxic protein tau, which builds up in patients with Alzheimer’s disease…

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Scientists at The Florey have developed an mRNA technology approach to target the toxic protein tau, which builds up in patients with Alzheimer’s disease and other dementias. 

Credit: Supplied by The Florey

Scientists at The Florey have developed an mRNA technology approach to target the toxic protein tau, which builds up in patients with Alzheimer’s disease and other dementias. 

To date, mRNA has been predominantly used for vaccines, including those used to fight COVID-19. 

New research published today in Brain Communications establishes The Florey as a key player in the mRNA field, with Dr Rebecca Nisbet taking the technology in a new direction. 

“This is the first time mRNA has been explored for use in Alzheimer’s disease,” Dr Nisbet said. “Our work in cell models demonstrates that this technology can serve purposes other than vaccine development.”  

She likened mRNA to an instruction manual for cells.  

“Once delivered to the cell, the cell reads the mRNA and makes an antibody.”  

The Florey team used mRNA to instruct cells in cell models to create RNJ1, an antibody Dr Nisbet developed to target tau, a protein that clumps in the brain cells of dementia patients. 

“This is the first time, to our knowledge, a tau antibody has been able to directly engage tau within the cell.” 

First author on the paper, PhD student Patricia Wongsodirdjo said: “Our technique can be applied to any therapeutic antibody, and we envision that this strategy, when combined with nanoparticle packaging, will enhance targeting of toxic molecules in the brain and improve patient outcomes compared to conventional strategies.” 

Dr Nisbet said RNJ1 still needed further research. 

She said emerging Alzheimer’s treatments, such as lecanemab, which is approved in the USA and under consideration in Australia, are promising but expensive to make and are not an efficient way of getting an active antibody into brain cells. 

“With conventional antibodies, such as lecanemab, the small amount of antibody that does enter the brain can remove some harmful plaque that lies outside our brain cells but can’t access toxic proteins such as tau, which is located in our brain cells,” Dr Nisbet said. 


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Initial claims remain somnolent, while continuing claims pop slightly

  – by New Deal democratThe divergence in the trends between initial and continuing claims continued this week, as the former continued their somnolent…

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 - by New Deal democrat


The divergence in the trends between initial and continuing claims continued this week, as the former continued their somnolent good news, while the latter had a slightly disconcerting pop.

Initial claims declined -2,000 to 210,000, and the four week average declined -750 to 211,000. On the other hand, with the usual one week delay, continuing claims rose 24,000 to 1.819 million:



The first two are in the same range they have been in for the past 4 to 6 months, while continuing claims are at their highest number but for 2 weeks in the past two years.

On the more important YoY basis for forecasting purposes, initial claims are down -9.5%, and the four week average is down -7.0%, the best YoY comparison in the past 12 months. Continuing claims are up 7.2%, but this is the second lowest YoY comparison in the past 12 months:

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Now let’s update the forecast of the Sahm rule. With last month’s 2 year high in the unemployment rate, I’ve been wondering whether, because unemployment includes both new and existing job losses, it followed continuing claims more than initial claims (although initial claims leads both). The historical graphs, which I posted two weeks ago so I won’t repeat now, indicated that continuing claims also lead the unemployment rate, although with much less of a lead time.

With that in mind, here is this week’s update of the post-pandemic record for the past two years on a monthly YoY% basis (unemployment rate YoY shown in red):



Since on a monthly basis so far initial claims are significantly lower YoY, and continuing claims a little over 7% higher, I expect the unemployment rate to be either unchanged or slightly higher YoY in the next several months. This would take it back down to the 3.7% area.

Here’s the same comparison on an absolute rather than YoY basis:



This similarly suggests a slight decline in the unemployment rate to 3.7% or 3.8%. Since the lowest three month average of the unemployment rate in the past 12 months was 3.5%, it would take an increase to 4.0% averaged over three months to trigger the Sahm rule. Both initial and continuing claims indicate that is not going to happen in the immediate future.

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Initial claims remain somnolent, while continuing claims pop slightly

  – by New Deal democratThe divergence in the trends between initial and continuing claims continued this week, as the former continued their somnolent…

Published

on

 

 - by New Deal democrat


The divergence in the trends between initial and continuing claims continued this week, as the former continued their somnolent good news, while the latter had a slightly disconcerting pop.

Initial claims declined -2,000 to 210,000, and the four week average declined -750 to 211,000. On the other hand, with the usual one week delay, continuing claims rose 24,000 to 1.819 million:



The first two are in the same range they have been in for the past 4 to 6 months, while continuing claims are at their highest number but for 2 weeks in the past two years.

On the more important YoY basis for forecasting purposes, initial claims are down -9.5%, and the four week average is down -7.0%, the best YoY comparison in the past 12 months. Continuing claims are up 7.2%, but this is the second lowest YoY comparison in the past 12 months:

.

Now let’s update the forecast of the Sahm rule. With last month’s 2 year high in the unemployment rate, I’ve been wondering whether, because unemployment includes both new and existing job losses, it followed continuing claims more than initial claims (although initial claims leads both). The historical graphs, which I posted two weeks ago so I won’t repeat now, indicated that continuing claims also lead the unemployment rate, although with much less of a lead time.

With that in mind, here is this week’s update of the post-pandemic record for the past two years on a monthly YoY% basis (unemployment rate YoY shown in red):



Since on a monthly basis so far initial claims are significantly lower YoY, and continuing claims a little over 7% higher, I expect the unemployment rate to be either unchanged or slightly higher YoY in the next several months. This would take it back down to the 3.7% area.

Here’s the same comparison on an absolute rather than YoY basis:



This similarly suggests a slight decline in the unemployment rate to 3.7% or 3.8%. Since the lowest three month average of the unemployment rate in the past 12 months was 3.5%, it would take an increase to 4.0% averaged over three months to trigger the Sahm rule. Both initial and continuing claims indicate that is not going to happen in the immediate future.

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Whiskey Rich: Luxury Liquor Trumps Stocks & Art Over Past Decade

Whiskey Rich: Luxury Liquor Trumps Stocks & Art Over Past Decade

Some of the world’s ultra-wealthy spend their money on luxury goods…

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Whiskey Rich: Luxury Liquor Trumps Stocks & Art Over Past Decade

Some of the world’s ultra-wealthy spend their money on luxury goods such as fine wines, expensive watches, or one-of-a-kind art pieces as a passion, but others consider them investments - and their returns do often end up paying off.

Visual Capitalist's Marcus Lu dives into the 10-year performance of various luxury good classes as of Q4 2023, according to the Knight Frank Luxury Investment Index released as part of the 2024 Wealth Report. The 10-year return of the S&P 500 was included for additional context.

Rare Whisky Bottles Have Outperformed the S&P 500 Since 2013

Knight Frank’s index uses the weighted average of each individual asset, tracking sales of reference brands and pieces for each asset.

Over the past 10 years, rare whisky (or whiskey, depending on where it was made) has been the best performing luxury asset, appreciating by 280% and even besting the S&P 500.

Numerous sale records have been broken at auctions since COVID-19, with collectors sometimes shelling out millions for a single bottle. In November 2023 for example, a bottle of The Macallan Valerio Adami 60 Year Old (of which only 40 bottles were produced) sold for $2.7 million at a Sotheby’s auction. Before bidding commenced, Sotheby’s had given the bottle a high estimate of $1.5M.

Fine wine and luxury watches were the next two best performing luxury goods by 10-year returns, at +146% and +138% respectively.

At the bottom were jewelry (+37%), such as rings and necklaces, and colored diamonds (+8%), including rare pink and blue diamonds.

Tyler Durden Wed, 03/27/2024 - 23:20

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