There's a Battle Being Fought Between the ScoliScore Folks and the ICONS Folks

[LindaRacine]

Most of you already know about ScoliScore, the Axial Biotech test that can help certain populations of kids with scoliosis, determine their risk of curve progression.

But, a new test could soon be on the market. The following paper was presented by Alain Moreau (Universite de Montreal), at the SRS meeting that ended earlier today.

High Circulating Levels of Osteopontin are Associated with Idiopathic Scoliosis Onset and Spinal Deformity Progression

Introduction: We hypothesized that scoliosis development in patients with idiopathic scoliosis and different melatonin-deficient animal models could be induced by a similar mechanism involving a common downstream effector regulated by melatonin. Indeed, the study of the molecular changes occurring in pinealectomized chickens revealed an increased production of OPN, at the mRNA and protein levels, in paraspinal muscles of scoliotic chickens. Therefore, we investigated the involvement of OPN, a multifunctional cyktokine, in IS pathomechanism.

Methods: A group of 320 consecutive patients with IS were compared with 120 healthy control subjects and 82 asymptomatic offspring, born from at least one scoliotic parent, who are considered at risk of developing this disorder. Plasma OPN and soluble CD44 receptor (sCD44) levels were measured by enzyme-linked immunosorbent assays. Contributions of OPN and CD44 receptors to idiopathic scoliosis were validated using C57BI/6j mice, a well known scoliosis animal model.

Results: Mean plasma OPN levels were significantly increased in IS patients and correlated with disease severity, with average values of 743+326ng/mi and 975+389ng/mi for moderated (10-44 degree) and severe (>45 degree) spinal deformities, respectively, when compared to the healthy control subjects. All transgenic C57Bi/6j mice devoid of OPN or CD44 receptor were protected against scoliosis, contrasting with wild-type ones.

Conclusion: Our clinical data and experiments on animals demonstrate that OPN is essential to induce scoliosis formation and curve progression through interactions with CD44 receptors, thus offering a first molecular concept to explain the pathomechanism leading to the asymmetrical growth of the spine in idiopathic scoliosis.

Significance: Plasma OPN and sCD44 values could be useful markers for diagnosis of IS and prognosis of curve progression

In a discussion with Dr. Moreau after his presentation, he mentioned that it's believed that environmental factors could potentially affect the levels of osteopontin in humans.

Watch this site for developments:

http://www.famill.chu-sainte-justine..._UNITE_rc=9005

[Dingo]

Osteopontin

Mean plasma OPN (Osteopontin) levels were significantly increased in IS patients and correlated with disease severity

Osteopontin

Role in autoimmune diseases
OPN has been implicated in pathogenesis of rheumatoid arthritis. For instance, researchers found that OPN-R, the thrombin-cleaved form of OPN, was elevated in the rheumatoid arthritis joint16. However, the role of OPN in rheumatoid arthritis is still unclear. One group found that OPN knock-out mice were protected against arthritis. while others were not able to reproduce this observation. OPN has been found to play a role in other autoimmune diseases including autoimmune hepatitis, allergic airway disease, and multiple sclerosis.

Role in cancers and inflammatory diseases
It has been shown that OPN drives IL-17 production; OPN is overexpressed in a variety of cancers, including lung cancer, breast cancer, colorectal cancer, stomach cancer, ovarian cancer, melanoma and mesothelioma; OPN contributes both glomerulonephritis and tubulointerstitial nephritis; and OPN is found in atheromatous plaques within arteries. Thus, manipulation of plasma OPN levels may be useful in the treatment of autoimmune diseases, cancer metastasis, osteoporosis and some forms of stress.

Research has implicated osteopontin in excessive scar-forming and a gel has been developed to inhibit its effect.

[Dingo]

my 2 cents

The blood test is going to replace the genetic test because it is more useful in almost every way. I believe it's much less expensive as well.

To the best of my knowledge the genetic test only works for adolescent girls. The blood test works for everyone.

The genetic test calculates the risk of curve progression in adolescent girls who already have Scoliosis.

The one time blood test determines if a child (or adult) has the nervous system disorder that leads to Scoliosis.

A second type of blood test is taken twice (or more) per year to determine the risk of curve progression.

These blood tests will be a tremendous addition to scientific research on Scoliosis. Now that scientists have a simple blood test they will be able to determine at what age the nervous system "breaks". This should help them determine what causes Scoliosis.

[leahdragonfly]

Thanks for the link, Linda. I find the idea of the blood test very promising. Dingo, I think you may be jumping ahead a little, though. For one thing, everyone in the study who was not a control (and thus did not test positive) had at least one parent with scoliosis. So it is not possible to generalize these results to those without a scoliotic parent without further testing.

Also, it doesn't sound to me like the test has predictive ability at this time. It says that the blood test scores correlated with the severity of the disease, so basically the blood test numbers rise as does the cobb angle. At that point you don't really need a blood test, since you can measure the rise in the cobb. So it would be great to find a blood test that gives elevated numbers long before the cobb angle rises--that is where a blood test would have great value. It's encouraging to see research in this direction, though.

[Dingo]

Osteopontin and lung disease

Genetically removing the osteopontin protein prevents lung diseases

In the study, researchers induced COPD features in mice and then compared symptoms experienced by mice with osteopontin and those without. The mice without the protein had less inflammation and lung disease. "The lack of osteopontin in the mice prevented the COPD features,"

---

Just a few quick google searches tells me that osteopontin is implicated in numerous diseases such as lung disease, cancer and autoimmune disease which are all closely related to inflammation.

Exercise, low stress, sleep (in a dark room), healthy foods including fish oil are all known to reduce inflammation in the body.

From what I've read online The Gold Coast Cure is an excellent, scientifically valid book on the subject.

[Pooka1]

I'd like to see some of these molecular types address themselves to the fact that most T curves are to the right. I mean what about the biochemistry would produce that result? If it was straight biochemistry, wouldn't you expect an equal proportion of right and left T curves?

There is some deep control on this like there is a deep control on why the heart is on the left side of the chest. I think this is the homeobox stuff that controls basic body plans but I don't really know.

Love,
so NOT a biologist

[Dingo]

Osteopontin

Molecule linked to autoimmune disease relapses identified

“When I saw that all mice with EAE relapsed and died from the disease after about a month of osteopontin administration, I was surprised,” said Hur, the study’s first author who is now a postdoctoral scholar at Caltech. “I got a strong belief that a high level of osteopontin in patients’ blood and tissue is a major contributor of the relapse and progression of the disease.”

[concerned dad]

Is there a relationship between Osteopontin and Melatonin?

[HaleyMom]

I find the idea of the blood test very promising. Dingo, I think you may be jumping ahead a little, though. For one thing, everyone in the study who was not a control (and thus did not test positive) had at least one parent with scoliosis. So it is not possible to generalize these results to those without a scoliotic parent without further testing.

Also, it doesn't sound to me like the test has predictive ability at this time. It says that the blood test scores correlated with the severity of the disease, so basically the blood test numbers rise as does the cobb angle. At that point you don't really need a blood test, since you can measure the rise in the cobb. So it would be great to find a blood test that gives elevated numbers long before the cobb angle rises--that is where a blood test would have great value. It's encouraging to see research in this direction, though.

Hi Gayle
The investigators actually filed a patent (WO/2008/119170) on their blood test back in 2008 claiming that their test is in fact predictive. In the patent, they recommend screening starting at age 3. While the patent has more data than described in the abstract Linda posted, the fact that the test is not yet on the market suggests more research is needed.

Dingo may find it interesting that the investigators also suggested in their patent that selenium supplements provide a natural way of reducing OPN levels

[LindaRacine]

Hi Gayle
The investigators actually filed a patent (WO/2008/119170) on their blood test back in 2008 claiming that their test is in fact predictive. In the patent, they recommend screening starting at age 3. While the patent has more data than described in the abstract Linda posted, the fact that the test is not yet on the market suggests more research is needed.

Dingo may find it interesting that the investigators also suggested in their patent that selenium supplements provide a natural way of reducing OPN levels

Dr. Moreau made it sound like the test was pretty close to coming to market.

[Dingo]

selenium

HaleyMom

Thanks so much for the Selenium mention! I've been looking all morning for a supplement or activity that might lower Osteopontin levels.

The following link on Selenium is awesome!!!

National Institutes of Health: Office of Dietary Supplements
Dietary Supplement Fact Sheet: Selenium

concerned dad

Is there a relationship between Osteopontin and Melatonin?

I can't tell for sure, I'm still looking. I found one link that (I think) indicated that Melatonin supplements might INCREASE osteopontin levels. The study seemed to indicate that this was a good thing because it meant extra bone growth. However this was from a supplement and I think the test was in a pitri dish, so I don't know how applicable it is. In fact I think they were simply trying to determine which hormones triggered bone growth.

[Dingo]

test going to market

LindaRacine

Dr. Moreau made it sound like the test was pretty close to coming to market.

Over the past year I've been in contact with the team in Canada and the blood tests will be available in the USA relatively soon. By relatively soon I mean maybe within a year.

[Dingo]

curve to the right

Pooka1

If it was straight biochemistry, wouldn't you expect an equal proportion of right and left T curves?

The body is not perfectly symmetrical. The spine bends towards the direction of least resistance which is probably towards the right in most cases.

[Dingo]

Selenium link

Another great Selenium link

National Institutes of Health: Selenium

BTW I've been looking at Selenium supplements and this stuff appears to be the cheapest stuff on earth.

[Ballet Mom]

Wow, this is really fascinating stuff! How wonderful that there is so much research going on in scoliosis at this time that there are two tests that may end up helping these kids. And to think that

a first molecular concept to explain the pathomechanism leading to the asymmetrical growth of the spine in idiopathic scoliosis

has been possibly determined, just wow!

Also I found this link: http://www.ingentaconnect.com/conten...dgq9rsh2.alice

Through cytokine functions, OPN supports immune responses against Mycobacteria and viruses such as herpes simplex virus.

And Dingo just pointed out that chickenpox is a herpes virus. So it could very well be that the higher level of OPN coincides with the immune response to a chickenpox infection (or others), which usually occurs before the age of ten, the time when most scoliosis cases are found. That would be an interesting angle to research, although it looks like they are well into researching all this stuff...wonderful!

And tuberculosis is a mycobacterium, and it was linked to spinal disease also.