Alzheimer’s, Lung Cancer - Blood Test for Early Diagnosis In the Pike

This will be an interesting exercise for me...

99.9% of credit for this thread goes to the incomparable member Soficrow who was unable to bring it to you for technical reasons... I am only the conduit and will try my best to refrain from corrupting her work with any superfluous verbosity. She has asked me to pass this along - and included some insightful notes that I try to include while remaining true to her journalistic intent

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Early diagnosis is the "Holy Grail" because chronic diseases like Alzheimer’s and cancer progress silently for decades before showing clinical symptoms. In theory, early diagnosis will lead to early treatment and delayed progression, if not a cure.

Newly-discovered "biomarkers" make it possible to diagnose these diseases in their earliest stages, and more are being found with regularity. However, scientific breakthroughs are not translating into early diagnosis, partly because the technology needed to run the tests is prohibitively expensive - the costs are too high for use in routine diagnostics.

Leading the quest to find the early-diagnosis Holy Grail are Integrated Diagnostics and Agilent Technologies, Inc - two companies who just teamed up to combine their resources, including "fast liquid chromatography and ultra-sensitive ion funnel triple quadrupole mass spectrometry."

Agilent and Integrated Diagnostics plan to commercialize early diagnosis. Focusing on protein and peptide biomarkers of disease, the combined technologies promise the opportunity to screen for several hundred biomarkers in a single test - allowing new biomarkers to be added as soon as they are discovered - and opening the door for early diagnosis of all the pandemic chronic diseases including cancer, obesity, heart disease, asthma and other lung diseases, diabetes, Alzheimer's and other dementias.

Integrated Diagnostics is creating large-scale, blood-based molecular diagnostics that leverage advances in proteomics and genomics to detect diseases such as lung cancer and Alzheimer’s at their earliest stages. …

…to rapidly turn medical breakthroughs into diagnostic assays by combining efforts to focus on protein and peptide biomarkers of disease.

…“… to realise the advantages of using a single technology platform from discovery and verification through to commercialisation.”

…The technology opens the possibility of screening for several hundred biomarkers in a single assay, in a very high-throughput and quantitative fashion…

www.labmate-online.com... ease_detection/18820/

Soficrow's notes are well worth consideration so forgive my attempts to bring them to you intelligently.... (that'll teach her to trust someone else with her work!

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On the surface this all sounds wonderful. But questions...

The earliest stages of chronic disease are marked by misfolded proteins - these are the "biomarkers" that can be identified, described, measured and quantified.

The industry and profession calls them "biomarkers"... but for my sake I have to think of them as 'recognizable' chemical structures - molecular shapes with qualities that set them apart from other molecular structures. Many organic molecules are, after all, chains of atoms - with the electrical characteristics of each atom contributing to how those molecules 'bunch up' or 'stretch out' - a process called "folding." When (or if) they kink and fold improperly they are also called "Prions" because their behavior in a cell becomes almost identical to a discrete and separate entity - or disease - within a cell or a biological system.

Soficrow asks:
WHERE DID THE BIOMARKERS (prions) COME FROM? WHAT CREATED THEM?

Why do the proteins "misfold" after all? Cosmic radiation? Foreign chemicals within the cell? Perhaps evolution? I will leave this to one of our many erudite and lucid members to expand.

Soficrow asks:
BESIDES COST, WHAT'S REALLY BLOCKING EARLY DIAGNOSIS?
….considerations: overpopulation; NCD pandemic; sheer numbers, costs

I hope I can be forgiven the cynicism of suggesting that "intent" is blocking early diagnosis. Assuming that many diseases could be much less catastrophic - and thus less profitable - were they detected early enough; the impetus of research is in novel molecular design of pharmaceuticals; and not necessarily anything else. "Cures" are out of the question - of course.

But perhaps Soficrow is on to something considering that prions may well be part of some evolutionary process which includes 'extinction' as part of the options on the table.

EARLY DIAGNOSIS, THEN WHAT?
Soficrow points to a WONDERFUL thread which any interested in such matters must visit.

McMaster researchers reverse Huntington's disease in mice

Soficrow asks:
WHO GETS TREATED? WHO DOESN'T? WHO DECIDES? - economic criteria

Soficrow gets to the human heart behind the issue. Suddenly (in a perfect world) whole swaths of potential diseases and susceptibilities can be presented to 'patients' about their 'potentially undeveloped medical condition' - are they considered then sick? Will healthcare treat them proactively, or force them to pay for future expenses which have not yet come to pass? What if the condition is not life threatening but debilitating... at what point are they disabled? It's another can of worms which we didn't foresee.

Soficrow has more on her mind... :
THE PROBLEMS WITH EARLY DIAGNOSIS
Other obstacles also restrain early diagnosis, discussed below.
IS IT GENETIC? WHAT IS "GENETIC SUSCEPTIBILITY"?
WHAT'S THE POINT OF DIAGNOSING IF WE CAN'T CURE THE DISEASE?

Dang girl!.. you're killing me. To say "I don't know." is as much as I can muster considering how our society makes itself predictable only to a point. Diagnosing that in later life a fetus will develop Alzheimers wouldn't appear to be just cause to change to course of its life... but some people would... or worse. Insofar as a genetic susceptibility... how will that information be guarded, used, shared? I would like to think we could be gentle stewards of our own people... but from what history teaches us... well... it's a depressing outlook.

I hate to be the one to break it to you, but wwe're ALL cooking up weird diseases in our precious little bods - except maybe the privileged few who've lived their entire lives in a bubble, unexposed to any synthetic chemicals, concentrated organic chemicals, nanoparticles or anything else.

It is natural for proteins to misfold in response to environmental changes and new exposures - the only way to stop the process is to stop adding new # to the environment - stop making chemical products for "personal hygeine," stop adding chemicals to food and drink.

Somehow... this doesn't seem to be in the cards for us...

It's counter-intuitive, but sick people and their progeny are the best equipped to survive in our polluted world - and the most likely to ensure our species' survival.

You may be right... I'll let you expand when the opportunity arises....

I'll have to come back to this , but let me try and sort through this .

WHERE DID THE BIOMARKERS (prions) COME FROM? WHAT CREATED THEM?

IS IT GENETIC? WHAT IS "GENETIC SUSCEPTIBILITY"?

From what I am understanding prions are normal proteins that become mutated , have the ability to bypass our immune response , and become infectious. These proteins can be ingested through contamination ( meat,flesh protein that has turned into infectious/mutated prion.)

Hereditary human prion disease Approximately 10-15% of people with prion disease have a genetic form. Genetic CJD is a single gene disorder due to mutations in the prion gene (PRNP) on chromosome 20. Presently more than 20 alterations in the DNA sequence in the gene have been reported. The characteristics of the disease correlate with the different mutation types. Several other changes in the PRNP gene (called polymorphisms) do not cause prion diseases, but may affect a person's risk of developing these diseases or alter the course of the disease.

More on Heredity here

Prions were first discovered in the late 60's and met with much ridicule by the scientific community ...

The hypothesis that prions are able to replicate without a genome and to cause disease violated all conventional conceptions and during the 1980s was severely criticized. For more than 10 years, Stanley Prusiner fought an uneven battle against overwhelming opposition.

www.nobelprize.org...

You ask what's the point if we can't cure the disease? I say , because scientists have MUCH MUCH more research to do before they can figure out a way to cure it , they didn't even accept it's existence till a short while ago. In the meantime , early detection can help with stall/slow the disease and I'm sure it HELPS with the studying process.

Very interesting, I'm sorry if I just told you what you already know . I will be back tonight to did through this some more

reply to post by Maxmars


Thanks so much Maxmars. Unfortunately, this is a huge topic and I can't do it justice right now. Sorry.

For starters though, this marriage of technologies is what's needed to make "personalized medicine" a reality. And we do need our medicine to be personalized - there is no magic bullet; one size does NOT fit all; and blockbusters always fail. One of the main reasons is that our bodies routinely "personalize" any bug, virus, bacteria or other microbe that gets inside us - so the response too, must be personalized.

As it happens, Agilent and Integrated Diagnostics are not the only companies looking to commercialize early diagnosis, and move personalized medicine forward. A recent ($9500.00) report from the Venture Planning Group summarizes the market in hematology.

Future US Hematology and Flow Cytometry Market Outlook
Report Details:
Title: Future US Hematology and Flow Cytometry Market Outlook
Published: February, 2012
Pages: 275
Price: US$ 9,500

New research report "Future US Hematology and Flow Cytometry Market Outlook" prepared by Venture Planning Group has been recently published by Market Publishers Ltd. The report reveals that commercialization of innovative products is likely to drive the future growth in the market, and the US will remain the biggest market for hematology.

London, UK (PRWEB) February 28, 2012

Increasing research and commercialization in the field of life sciences such as proteomics, genomics, pharmacogenomics, and stem cell research have resulted in a boosting of high-throughput technologies such as the flow cytometry market. However, several constraints, such as increased equipment cost, are hindering the market growth.

Also see: www.prweb.com...

On the subject of prions, yesterday's conference in France covered off some of the more up-to-date issues in neuroscience.

What at first seemed an unusual mechanism restricted to a rather rare group of diseases has now become central to the study of all neurodegenerative conditions: the pathogenic proteins that characterise these diseases all seem to behave like prions. The implications for understanding how these diseases are transmitted through the nervous system and the possibility that environmental contamination may account for the sporadic forms of these diseases, as well as therapeutic possibilities, were among the topics discussed by the thirteen international experts, including two Nobel Prize winners, at the 27th annual colloquium on Alzheimer's disease, hosted by the Fondation IPSEN.

reply to post by Maxmars


Thanks for visiting my thread Soficrow and recommending it. Thanks too Maxmars for the applause.

I knew a tiny bit about prions, but what I find interesting is the plan to keep adding markers in order to provide an all-encompassing screening tool. It's a very comforting idea. However, as we've been duped so many times by selfish corporate interests, I wonder just how prohibitive the cost would be . I also think it could and would be used for selective procreation just as in some places the ultrasound is used to for gender selection.

In one lab, one of the markers they're working on is about shortness in people. I haven't yet looked into what all the markers are, but I do hope to see one for incontinence, as I know that many people believe it runs in families (pun accidental but I'll let it be :duh Although if they discover one, many big corporations would lose lotsa lotsa money if the screening were to lead to successful cell therapy.

reply to post by aboutface


Thanks aboutface. ....As you've probably realized, the marker for Huntington's, GM1, is a protein. When it misfolds, it gets inappropriately involved with amyloid, which creates plaques and results in Huntington's. More or less.

...This 'blood test' idea is that as new misfolded proteins, peptides, enzymes and other precursors are identified, they can easily be added to the test array - a very good thing because slight individual variations in individuals' diseases will more likely be identified and correctly treated.

....I share your concerns that such tests might be used to "weed out" the bad seeds, and shudder to think what some people might do with the information. This is one reason I really want to emphasize that: prions are an evolutionary mechanism; prion diseases likely confer as-yet unseen benefits; and it's a complete misapprehension to think that (protein) conformational diseases represent genetic "failures."

reply to post by soficrow

GM1 was identified as a lipid. You're saying it's a protein. Is it a lipoprotein perhaps? As you can see, my knowledge is limited in biochemistry.

Originally posted by aboutface
reply to post by soficrow

 

GM1 was identified as a lipid. You're saying it's a protein. Is it a lipoprotein perhaps? As you can see, my knowledge is limited in biochemistry.

Mine too, lol - am always playing catch-up - might be a lipoprotein or protein-lipid complex - the link I provided says Monosialoganglioside GM1 protein (ab111645) is a protein.

...There are complex interactions between proteins and lipids, proteins and carbs, and all three together - it may be that the identities are blurred during the folding processes. Also, it may be that the name-game now decrees all molecules be called proteins when they misfold, particularly when/if they're interacting...

Several years ago, a paper described a sugar as folding and misfolding (forget which one), thus suggesting that other molecules besides proteins rely on shape to determine function. I haven't followed up but keep meaning to research the topic further.

However, if sugars and other carbohydrates can misfold in ways that affect function, like proteins, there is little doubt that lipids can too. In fact, I have another vague memory of another paper describing lipid misfolding, and an equally vague recollection of its role in obesity - no hard facts, info or references though. Sorry.

....I focus almost exclusively on proteins but my general perception is that ALL molecules fold and so, are also subject to misfolding - with an attendant effect on function. Maybe you could do some follow-up on this one and share your info?

Thanks, sofi