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Thread: Drugs with anti-inflammatory properties may help scoliosis?

  1. #16
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    When my daughter was ten and eleven, her ballet teachers used to tell me that they expected great things from her. At twelve, she developed progressive scoliosis and any expectation of greatness fell apart. I have watched her for almost three years completely lose her balance and soundness in ballet. A truly heart-wrenching experience.

    Until last December, I could watch my daughter performing a penchee ( http://www.abt.org/education/diction...ms/penche.html ) and her supporting foot and ankle would just wobble back and forth and she would be unable to hold her other leg up. Her ballet teachers were obviously quite frustrated as by this age all other students in the class could perform it perfectly.

    This summer, after the accutane and also probably close to the end of her growth spurt, she is rock solid in ballet. It has been an amazing transformation. She can do everything now including a beautiful penchee en pointe (on her toes). According to her, three artistic directors from three major foreign ballet companies have paid close attention to her during class at her summer intensive. She is thrilled and so am I.

    I have no idea if the accutane has had anything to do with this transformation, but I think there are enough things jumping up and down screaming "notice me" that has occurred recently, that I am going to write a letter to Dr. Collins at NIH describing my daughter's experience and suggesting maybe a study to see if there's anything to it. Hopefully with his background he might actually be interested and he certainly has the power to start a study. At least I won't have left this very interesting sequence of events to be buried in the e-dust of this site and no one following up on it.

    Interestingly enough, because the makers of accutane have recently been losing major lawsuits regarding the safety of their drug, a study has come out testing a "safer" version of accutane. It would be a wonderful confluence of events if a safer version of accutane coincided with a study for scoliosis.

    Anyhow, nothing may come of it, but I shall do my part to help in the research of possible cures for scoliosis. It's certainly worth a shot anyway.

  2. #17
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    Inflamation & Scoliosis

    Was this coincidence or something more? There was an oral presentation at SOSORT 2005 that makes me wonder.

    From: The association between IL-6 and MMP-3 gene polymorphisms and adolescent idiopathic scoliosis: a case-control study


    Background

    The nucleus pulposus of scoliotic discs respond to exogenous stimuli by secreting interleukin-6 (IL-6) and other inflammatory cytokines. The association between matrix metalloproteinases (MMPs) and disc degeneration has been reported by several investigators. A human MMP-3 promoter 5A/6A gene polymorphism regulates MMP-3 genes expression, while the G/C polymorphism of the promoter region of IL-6 gene influences levels and functional activity of the IL-6 protein.

    Methods

    We conducted a case-control study to investigate whether the 5A/6A polymorphism of the MMP-3 gene and the G/C polymorphism of the promoter region of IL-6 gene were associated with the susceptibility to develop AIS.

    Results

    The frequency of the 5A/5A genotype of MMP-3 gene polymorphism in patients with scoliosis was almost 3 times higher than in controls (30.2% vs. 11.2%, P 0.001). The frequency of the G/G genotype of IL-6 gene polymorphism in patients with scoliosis was almost 2 times higher than in controls (52.8% vs. 26.2%, P < 0.001). 5A/5A genotype of MMP-3 gene polymorphism and G/G genotype of IL-6 gene polymorphism are independently associated with a higher risk of scoliosis (odds ratio, respectively, 3.34 and 10.54).

    Conclusion

    This is the first study performed to evaluate the possibility that gene variants of IL-6 and MMPs may be associated with scoliosis. This study suggests that MMP-3 and IL-6 promoter polymorphisms constitute important factors in the genetic predisposition to scoliosis.
    Last edited by mamamax; 08-15-2010 at 09:10 AM.
    Idiopathic, from the Latin meaning: we're idiots 'cause we can't figure out what's causing it (TV Dr. House, MD)

    I'm not weird ... I'm simply - multifactorial

  3. #18
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    Exogenous Factor

    I had to look that one up! From: http://en.wikipedia.org/wiki/Exogeny

    Of course, this is leading back to all things Dingo


    In biology, an exogenous factor is any material that is present and active in an individual organism or living cell but that originated outside of that organism, as opposed to an endogenous factor.

    * Exogenous factors in medicine include both pathogens and therapeutics.
    * DNA introduced to cells via transfection or viral infection (transduction) is an exogenous factor.
    * Carcinogens are exogenous factors.
    Idiopathic, from the Latin meaning: we're idiots 'cause we can't figure out what's causing it (TV Dr. House, MD)

    I'm not weird ... I'm simply - multifactorial

  4. #19
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    Great find Mamamax!!!

    The nucleus pulposus of scoliotic discs respond to exogenous stimuli by secreting interleukin-6 (IL-6) and other inflammatory cytokines.
    I have to admit that on a technical level this is way over my head. But theoretically speaking it makes perfect sense.

    For example a gene that protects the body from the flu virus may make it more susceptible to a cold virus.

    In this case genes may increase the secretion of inflammatory cytokines. This may protect the body from some diseases but increase the likelihood of other diseases like Scoliosis. In certain environments that may be a smart trade off because the Scoliosis trigger is uncommon or rare. That's how nature works.

    If scientists could determine what the environmental trigger was they could probably eliminate it with a vaccine or some other measure.
    Last edited by Dingo; 08-15-2010 at 12:48 PM.

  5. #20
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    Thanks mamamax, you are awesome! You are really diligent!

    I think there has to be an inflammatory response in scoliosis, because as Dingo has pointed out, osteopontin is greatly increased in scoliosis which is a part of the inflammatory process in humans. Perhaps your study is pointing out part of that inflammatory process!

    I think in my daughter's case, it still seems likely that there was some organism or inflammation independent of the causes in your study because she would still have the inflammation indicated in this study going on due to the fact that she still has a major structural curve of 29 degrees. But even though she still has the curve, all the instability in ballet has completely disappeared...directly after her use of accutane. It just seems too closely related to the accutane use to be something else. Of course, maybe the accutane really did affect and modify the inflammatory response directly...who knows?!

    If it turned out that accutane had some effect, it might open up other areas of research because I think Dingo pointed out that Alzheimers may possibly be caused by the herpes simplex virus (perhaps residing in the spinal ganglia). And how many oldtimers have been treated with accutane during their descent into dementia? None? Probably.

    I think it could be an exciting avenue of research...but who knows...I will just write my letter and hope it interests somebody at NIH.
    Last edited by Ballet Mom; 08-15-2010 at 03:03 PM.

  6. #21
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    Chronic urinary tract infections tell us a lot

    The nature of chronic urinary tract infections tells us a lot about chronic infection in general.

    Sciencedaily: Immune System Overreaction May Enable Recurrent Urinary Tract Infections

    Researchers showed in mice that severe inflammatory responses to an initial UTI cause bladder damage and allow infection to persist longer. After one to two weeks of infection, the bladder wall undergoes additional changes that leave mice more vulnerable to later infection.
    "Chronic bacterial cystitis is an infection that is actively reproducing, has established a persistent and significant foothold in the host's bladder and has prompted a sustained response from the immune system," says Hannan, a research instructor in pathology and immunology. "Despite all this, the infection is still well-tolerated by the mice."
    This phenomenon may be associated with heart disease, autoimmunity and many other common health problems like Alzheimers Disease (thanks for reminding me BalletMom). I wouldn't be surprised if chronic infections were ultimately connected to other diseases like Acne and Scoliosis. Dr. Moreau recently mentioned that exposure to harmful bacteria may be a factor in curve progression. (Source)

    This is nothing new to the scientific community. In the 1980s scientists proved that Peptic ulcers were caused by chronic infection with H Pylori and could be easily treated with antibiotics. Research also suggests that heredity plays a role in susceptability to ulcers.

    Epidemiology and genetics of peptic ulcer.
    Three lines of evidence support a genetic role: family studies, twin studies and blood group studies. Family aggregation occurs more commonly in patients with early-onset (less than 30 yr) of symptoms.
    The best physiological marker is still hyperpepsinogenemia I, which is transmitted by autosomal dominance, despite recent report of lower serum pepsinogen 1 after healing of Helicobacter pylori associated gastritis.
    Last edited by Dingo; 08-15-2010 at 10:05 PM.

  7. #22
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    Look at this study! And Parkinson's like illnesses run in my family too! Could the same thing be going on in scoliosis? http://www.bbc.co.uk/news/health-10956490


    The immune system may have a key role in the development of Parkinson's disease, say US researchers.

    In a 20-year study of 4,000 people, half with Parkinson's disease, the team found an association between genes controlling immunity and the condition.

    The results raise the possibility of new targets for drug development, Nature Genetics reports.

    Parkinson's UK said the study strengthened the idea that immunity is an important driver of the disease.

    The team were not just looking for a genetic cause of the disease, but also considered clinical and environmental factors.
    /
    /
    Inflammation

    Multiple sclerosis has already been shown to be associated with the same HLA genetic variant seen in the latest study in Parkinson's disease, the researchers said.

    It was already known that people who take anti-inflammatory drugs, such as ibuprofen, have a decreased risk of developing Parkinson's disease, which also supports the idea that the immune system has a role in the disease.

    But this protective effect is not the same for everyone, probably because of genetic differences.

    With better understanding of the link between Parkinson's disease, immunity and inflammation, it may be possible to design more effective drugs for treating the condition, the researchers said.

    "Over the years, there have been subtle hints that immune function might be linked to Parkinson's disease," said study leader Dr Cyrus Zabetian, associate professor of neurology at the University of Washington.

  8. #23
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    Good links!

    Ballet Mom

    Great links on Parkinsons and immunity. When Dr. Moreau mentioned that harmful bacteria might be connected to Scoliosis it probably shocked a lot of mothers who thought their kids had a genetic disease. Believe me, in the scientific community it was no surprise at all. That's where a lot of things are headed.

    Even Autism is being traced back to inflammation and immunity.

    Autistic kids have inflamed brains
    "These findings reinforce the theory that immune activation in the brain is involved in autism, although it is not yet clear whether it is destructive or beneficial, or both, to the developing brain," said Assistant Professor Carlos Pardo-Villamizar of Johns Hopkins, who led the study.
    Mother's flu could lead to mental illnesses
    WOMEN who catch the flu during pregnancy are up to seven times more likely to have a child with schizophrenia - and scientists believe they have finally figured out why. A rogue protein, interleukin 6 - produced when a pregnant woman is fighting a viral infection - may help trigger mental illnesses such as autism and schizophrenia in the child, US neuroscientist Paul Patterson said yesterday.
    Narcolepsy too.

    Immune fault 'link' to narcolepsy
    Dr Mignot said: "Narcolepsy is probably the result of a series of unfortunate events, starting with genetic predisposition, involvement of an environmental trigger such as an infection, then T-cell activation, then effects on many other arms of the immune system."
    Very few children are genetically programmed to become sick because natural selection wouldn't allow it. When a child becomes sick something bad happened to him or her. Most people don't realize it's that simple.
    Last edited by Dingo; 08-16-2010 at 11:23 AM.

  9. #24
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    The MMP-3 thing is kind of neat. I'd like to track that down a bit more.

    I want to issue a small word of caution about inflammation and what role it might play in scoliosis. I know you all are just chatting about links that you're finding but an increased amount of inflammatory cytokines in a patient population doesn't necessarily imply causation. Inflammation is also responsible for triggering good things in our body as well. In fact, an increase in IL-6 has also been shown after exercise. It's thought that the rise in IL-6 levels trigger the response of several anti-inflammatory cytokines as well as various growth factors. So as you read through things, just remember that something that initially sounds bad, like inflammation, might not be as bad as it sounds.

    Just my words of caution from the research side of things.

  10. #25
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    100% correct

    Skevimc

    So as you read through things, just remember that something that initially sounds bad, like inflammation, might not be as bad as it sounds.
    You are 100% correct. Humans wouldn't have genes that programmed for inflammation if it wasn't useful. From my reading it's the downside of chronic or acute inflammation that has the potential to cause serious health problems.

    A piston in an engine is very useful... until it slams through the cylinder head because you ran out of oil.

  11. #26
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    Very interesting! Looks like I'm a little behind the times...go figure!

    Accutane or isotretinoin is a retinoid. I guess maybe I need to contact some of these researchers and let them know and maybe they can expand their research to scoliosis! I really believe there must be a relation to what has happened with my daughter and her treatment with isotretinoin.

    http://www.bentham.org/car/openaccss...r6-3/014AT.pdf


    Towards Retinoid Therapy for Alzheimer’s Disease

    Conclusion:
    /
    Retinoids are required for the maintenance of the immune
    systems, and are very potent immunomodulators. They
    suppressively regulate various autoimmune disease states,
    and being different from simple immunosuppresants, work
    physiologically even when applied at high pharmacological
    concentrations.


    Retinoids are essential in the regeneration of neural cells
    and other tissues. Development of retinoids that are highly
    selective for individual RARs may contribute to the treatment
    of AD and other neurodegenerative diseases. Recently
    there came out a review emphasizing significant roles of
    retinoids for treatment of neurodegenerative diseases such as
    ALS, AD and schizophrenia
    [153]. We did not cover RXRs
    and RXR ligands here, though these may have a role in increasing
    the selectivity of retinoids, and they seem to have
    important roles in mental activities such as sleep regulation,
    reward-related behaviors [154-158].

    Retinoids were suggested long ago to have potential for
    the therapy of various proliferative diseases [159]. Some
    applications have been realized, and our task now is to extend
    the range of applications to neurodegenerative diseases,
    including AD
    .
    I'm editing to add this bit also...very interesting:

    Infection could be a cause for breakdown of immune
    system and trigger autoimmune diseases. There is a hypothesis
    that AD is an autoimmune disease caused by an infection,
    but others have doubted a role of viral or other infection
    [104-106]. The role of infection with herpes simplex, spirochetes,
    and chlamydophila in AD has recently been reviewed
    [67, 107-109]. A role of infection would be consistent with a
    recent report that a group of ALS patients showed an extremely
    high frequency of systemic mycoplasmal infections
    [110].


    Various routes of infection, such as gut, nasal, skin and
    lung, involving viruses, bacteria, specific proteins and
    chemical substances have been discussed. The olfactory vector
    hypothesis is that xenobiotics, including viruses and toxins,
    immunologically pull the trigger leading to neurodegeneration
    [106, 111]. This hypothesis is supported by the finding
    that olfactory dysfunction is a risk factor for PD and AD
    [111-113]. The normal differentiation and regeneration of
    olfactory-related cells are also regulated by retinoic acid, and
    vitamin A therapy in animals with olfactory system damage
    can accelerate functional recovery through RARs and retinoid
    X receptors (RXRs): retinoic acid supports the integrity
    of the olfactory system throughout life [114, 115]. The maintenance
    of olfactory function by retinoid may be preventive
    for the disease. Pathogens may elicit an autoimmune response
    without persistence of the initiating agent, environmental
    factors and nutrition being critical determinants of the
    onset.

    REGENERATION OF NEURAL CELLS
    A possible approach to neurodegeneration is neural stem
    cell therapy. It is now well established that cells in the central
    nervous system can regenerate under certain conditions.
    Advances in techniques to isolate and manipulate neural
    stem cells offer new scope for functional recovery after central
    nervous system injuries.
    Last edited by Ballet Mom; 08-16-2010 at 05:13 PM.

  12. #27
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    Here's another fairly recent article:

    http://www.sciencedaily.com/releases...0614151809.htm

    Potential Role For Retinoic Acid In Autoimmune And Inflammatory Diseases Identified

    ScienceDaily (June 18, 2007) — An important finding, which could eventually lead to a new therapeutic approach for treating autoimmune and inflammatory diseases such as rheumatoid arthritis, colitis, psoriasis and others, was announced today by researchers at the La Jolla Institute for Allergy & Immunology (LIAI). The studies, conducted in laboratory mice, demonstrated the role of retinoic acid, a substance derived when Vitamin A is broken down in the body, in regulating inflammation.

    In these studies, published in the journal Science, the LIAI researchers showed that by manipulating the amount of retinoic acid in mice, they could affect the number of pro-inflammatory T cells, a type of white blood cell responsible for several autoimmune and inflammatory diseases. The finding is an important first step that, if eventually found to be true in humans, points to the potential of a new avenue of therapies using retinoic acid to treat these diseases.

    "What's exciting about this finding is they've found that retinoic acid plays a role in modulating the switch between these two distinct (T cell) lineages -- the induced regulatory T cells, which are anti-inflammatory, and the TH-17 lineage, which promotes inflammatory responses, " said Casey Weaver, M.D., a University of Alabama, Birmingham, professor and prominent immunology researcher, who was key in the discovery of TH-17 in 2005.

    Further, Dr. Weaver said, the LIAI researchers had developed a "mechanism by which you can prevent the development of the (inflammatory) lineage. This is very exciting because it provides a potential pharmacological application for this finding."

    The LIAI team tested three approaches with retinoic acid. In one model, they injected the mice with retinoic acid, essentially giving them more of the substance than they would have through normal body processes. This suppressed the formation of pro-inflammatory T cells in the intestines of the mice, demonstrating that increases in retinoic acid reduced inflammation. In another approach, designed to test how reducing retinoic acid would affect inflammation, the team used an inhibitor to block retinoic acid in the mice.

    This led to the decrease of anti-inflammatory T cells, showing that reducing retinoic acid increased inflammation. In a third, particularly exciting approach, the scientists treated T cells with retinoic acid in a test tube. When put back into the mice, these T cells prevented the formation of inflammatory T cells in the mice. This is especially noteworthy because combining the retinoic acid and T cells outside the body may avoid possible side effects that are more likely when scientists attempt to manipulate body processes internally.

    "We found that you can control inflammation in a living animal with retinoic acid or you can treat cells with retinoic acid in a test tube and transfer them to the organism to suppress inflammation in vivo," said Dr. Cheroutre. "This may offer an important new avenue for treatment of autoimmune diseases like colitis and rheumatoid arthritis or other inflammatory diseases, as well as potentially providing a mechanism for the control of graft rejections, where you don't want the immune system to attack the grafted tissue."

    The finding was published in a paper entitled "Reciprocal Th-17 and regulatory T cell differentiation mediated by retinoic acid." Hilde Cheroutre, Ph.D., led the research team, entirely from LIAI, in which Daniel Mucida, Ph.D., and Yunji Park, Ph.D., were key contributors.
    Last edited by Ballet Mom; 08-16-2010 at 03:04 PM.

  13. #28
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    Oh my gosh, this is just endlessly fascinating! I love the internet! I think La Jolla is where it's all happening...need to write them.

    Perhaps retinoids are involved in congenital types of scoliosis also:

    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2235195/


    Retinoic acid (RA), the active form of vitamin A, plays a crucial role in stimulating nuclear receptor signaling during development. However, the developmental processes regulated by RA signaling are not well understood. This is pointed out by the recent discovery that RA controls left–right patterning during somitogenesis (Kawakami et al., 2005; Vermot et al., 2005; Vermot and Pourquié, 2005; Sirbu and Duester, 2006), a function that was totally unsuspected based upon what was known about RA function up to that point. These findings suggest that defective RA signaling may be responsible for human birth defects of the vertebral column, a topic which is discussed further below.
    /
    /
    The discovery that RA is required for synchronous left–right development of somites indicates that RA is required to generate a bilaterally symmetrical spinal column (Kawakami et al., 2005; Vermot et al., 2005; Vermot and Pourquié, 2005; Sirbu and Duester, 2006). RA-deficient mouse embryos are unable to undergo axial turning to achieve the normal fetal position (Vermot et al., 2005; Sirbu and Duester, 2006). Administration of RA maternally to RA-deficient mouse embryos restores normal axial turning and normal spinal column development (Sirbu and Duester, 2006). These studies thus provide evidence that a loss of RA synthesis during gestation causes spinal column birth defects, but that normal development can be restored by supplying an exogenous source of RA.These findings have implications for understanding the etiology of human spinal column birth defects. This may include birth defects such as scoliosis, an abnormal left–right bending of the vertebral column (Kane, 1977). Idiopathic scoliosis (scoliosis of unknown cause) is the most common type, accounting for 85% of all cases (Reamy and Slakey, 2001). Idiopathic scoliosis is present in 2–4% of children, and about 4 out of 1000 children develop spinal curves large enough to require treatment (Kane, 1977; Reamy and Slakey, 2001). Since scoliosis can run in families, some cases may be the result of a genetic defect (Miller, 1999; Sturm et al., 2001). Scoliosis may be caused by skeletal birth defects that result in hemivertebrae, whereby the left or right side of a vertebra fails to develop normally before birth (McMaster and David, 1986). As most individuals with hemivertebra have additional congenital abnormalities (cranial, cardiac, renal, intestinal, and skeletal) (Goldstein et al., 2005), the underlying defect could be a reduction in RA signaling, which is known to be required for development of all these tissues (Lohnes et al., 1994; Mendelsohn et al., 1994). Thus, either maternal vitamin A deficiency during pregnancy or an embryonic defect in metabolism of vitamin A to RA might be associated with increased risk of human vertebral defects.

  14. #29
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    Quote Originally Posted by Dingo View Post
    When Dr. Moreau mentioned that harmful bacteria might be connected to Scoliosis it probably shocked a lot of mothers who thought their kids had a genetic disease. Believe me, in the scientific community it was no surprise at all. That's where a lot of things are headed.
    Dingo, very interesting links, especially the autism one.

    Do you know if Dr. Moreau is doing research on specific drugs that might help scoliosis since he seems to view scoliosis as not just a genetic disease? Would he be interested in the possible retinoid aspect at all? Or maybe he already is researching it?
    Last edited by Ballet Mom; 08-16-2010 at 04:03 PM.

  15. #30
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    Quote Originally Posted by skevimc View Post
    The MMP-3 thing is kind of neat. I'd like to track that down a bit more.

    I want to issue a small word of caution about inflammation and what role it might play in scoliosis. I know you all are just chatting about links that you're finding but an increased amount of inflammatory cytokines in a patient population doesn't necessarily imply causation. Inflammation is also responsible for triggering good things in our body as well. In fact, an increase in IL-6 has also been shown after exercise. It's thought that the rise in IL-6 levels trigger the response of several anti-inflammatory cytokines as well as various growth factors. So as you read through things, just remember that something that initially sounds bad, like inflammation, might not be as bad as it sounds.

    Just my words of caution from the research side of things.
    Thanks for the words of caution, skevimc. We have actually discussed in the past that the inflammatory response is good, until it goes out of control. I think it was when we were talking about osteopontin as part of the inflammatory response in humans. i.e. Osteopontin is a good thing until it goes out of control? Anyhow, it's all just an absolutely fascinating field. I really wish I had majored in something different at this point in my life. I wish I could research this!

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