Rich--new study out linking SOD1 with ALS

Discussion in 'Fibromyalgia Main Forum' started by tooks, Jun 5, 2008.

  1. tooks

    tooks Member

    Hi Rich,

    I saw this abstract on the lastest CDC genetic study posting:

    "An upcoming paper from Drs. Hidenori Ichijo and Hideki Nishitoh (The University of Tokyo) and colleagues lends new and valuable insight into the genetics of ALS.
    Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease, is a rapidly progressive, fatal neurological disease involving the degeneration and death of motor neuron cells.
    ALS is one of the most common neuromuscular diseases worldwide, affecting as roughly 25,000 Americans, with an estimated 5,000 new diagnoses each year. The life expectancy of ALS patients is usually 3 to 5 years after diagnosis.
    5-10 percent of all ALS cases are inherited. About 20% of these familial ALS cases are the result of an inherited genetic mutation on chromosome 21, in the gene encoding for the superoxide dismutase 1 (SOD1) enzyme. SOD1 is an antioxidant that protects the body from DNA damage caused by the accumulation of free radicals within cells. However, several reports have demonstrated that mutated SOD1 toxicity is not due to decreased antioxidant activity, but rather to a 'gain of unknown toxic function'.
    In their upcoming paper, Dr. Ichijo and colleagues delineate how mutations in SOD1 lead to motor neuron cell death and the progression of ALS. The researchers characterized a molecular pathway by which mutated SOD1 contributes to the accumulation of malformed proteins inside the endoplasmic reticulum (ER) compartment of motor neuron cells. Beyond a certain threshold, this ER stress induces cell death.
    Interestingly, Dr. Ichijo's team found that the inactivation of certain key factors in this pathway could mitigate neurodegeneration and prolong survival in a mouse model of inherited ALS.
    Although not all familial ALS cases are due to the SOD1 mutation (and not all persons with a mutated form of SOD1 develop ALS), further insight into mechanism of the disease will undoubtedly aid in the development of an effective treatment for ALS."

    I've read that there are 3 types of SOD--1,2,& 3 and that it seems Pall is saying that it is the one in the mitochonria that is so important to us, which seems to be SOD2. I started taking Biotec Foods "Extra Energy Enzyme" which says it is a precursor to Superoxide Dismutase. It does give a boost, but is it boosting 1, 2, or 3?

    This is especially interesting to me because not only would I like to regenerate the mitochondria, but my uncle has recently been diagnosed with ALS. It looks like, by implication, compromised mitochondria are not directly related to ALS. Any thoughts!

    Thanks, Susan

    [This Message was Edited on 06/06/2008]
  2. richvank

    richvank New Member

    Hi, Susan.

    Thanks for posting this interesting abstract. It has been known for quite a while that there was an issue with SOD1 in ALS, but that it did not involve its antioxidant function. Now, according to this abstract, these researchers have discovered how the problem with SOD1 leads to death of the motor neurons. I'll have to get the full paper to see exactly what they did, but it sounds like an important development in understanding the pathogenesis of ALS.

    Yes, there are three type of SOD, and yes, SOD2 is the manganese-containing one that is present in the mitochondria. SOD1 contains copper and zinc.

    I don't know what the Extra Energy Enzyme product actually does. In the past, the recommendations for helping the SODs were to supplement the minerals they contain. I know that the Life Extension Foundation has a product that they claim helps SOD, also. I've always been puzzled by claims that an enzyme can be taken orally and will somehow get into the cells intact, because enzymes are proteins, and for the most part they are digested in the gut and enter the portal blood to the liver as di- or tri-peptides. I realize that some enzymes are absorbed intact, though, and that's the basis for use of digestive enzymes to treat inflammation, as with Wobenzym or bromelain or papain or other proteolytic enzymes. But in those cases, I think they only enter the blood, not the cells. So I still don't understand these claims. Maybe they enter cells by endocytosis. I would like to know more about this.

  3. tooks

    tooks Member

    Hi Rich,

    Thanks for the response re the product called Extra Energy Enzymes by Biotec Foods. (Some of us are taking it in hopes of improving mitochondrial function--it is said to be a precursor to Superoxide Dismutase.)

    To try to answer your question about how it gets through the digestive system, I copied sections from their patent proposal which go into it. Maybe you could comment cause if it sounds like the real thing, it could be a boon--If not, we are wasting our money.

    I have the whole document which I can send if this doesn't have the relevant info, but here is what I abstracted:

    1. A prebiotic mix containing dehydrated sprout powders from glycine max, zea mays,
    and triticum.turgidum, cyanocobalamin, dalpha tocopherol, and a probiotic mix described in claim 2, and prepared as described in claim 4 for delivery through the acids of the stomach and into the small intestines causing endogenous reaction of isoflavones consisting of genistein, daidzein, biochanin A, formononetin, Odesmethylangolensin, glycitin, and equol, in an amount sufficient to produce an upregulation of mammalian superoxide dismutase and catalase gene expression endogenously. Specifically, copper zinc SOD known as cellular SOD or SOD1, and manganese superoxide dismutase or SOD2, and extracellular SOD or SOD3.

    4. The administration of a therapeutically effective concentration of the prebiotic mix described in 1 and strains of lactic acid producing bacteria described in 2 within a pharmaceutically acceptable
    carrier suitable for administration to the gastrointestinal tract of a mammal, wherein said lactic acid producing bacteria is reacted with said prebiotic mix, resulting in increased promotion and growth of the equol and ODMA producing intestinal bacteria, in order to maximize endogenous production and absorption of selective estrogen receptor site modulators (SERM) that bind to estrogen receptor site
    beta (ER beta), with a higher affinity than to estrogen receptor site alpha.
    5. The composition according to claim 4 of the SERM consist of the isoflavones: genistein, daidzein, biochanin A, formononetin, Odesmethylangolensin, glycitin, and the endogenously produced isoflavone metabolites equol and ODMA.

    6. The composition of the pharmaceutically acceptable carrier in claim 4 is a cellulose coating selected from the group consisting of carboxymethylcellulose sodium methylcellulose, ethylcellulose, ethylmethylcellulose, hydroxyethylcellulose, or microcrystalline cellulose; and a pharmaceutical lubricant from the group consisting of stearic acid, magnesium stearate, aluminum magnesium silicate, sodium silicate, silicon dioxide and colloidal silicon dioxide.

    9. A method according to claim 4, wherein the SERM absorption results in upregulation of superoxide dismutase gene expression.

    10. The composition of the superoxide dismutase in claim 9 is the manganese superoxide dismutase (Mitochondrial SOD or SOD2) and ExtraCellular superoxide dismutase (EC SOD or SOD3).

    11. A method according to claim 1, wherein the premix in claim 8 blocks the absorption of iron (Fe) resulting increased cellular superoxide dismutase (cu/zn SOD or SOD1).

  4. richvank

    richvank New Member

    Hi, Susan.

    O.K., I see that they are not claiming that SOD is given in their supplement and is absorbed without being broken down. What they are claiming is that using a combination of prebiotic and probiotic, they can increase the gene expression of SOD. This is a new one on me. Maybe it works. I can't say I understand how it does that, though. But then, there are a lot of things I don't understand!:)-)

    Thanks for posting this.

  5. Forebearance

    Forebearance Member

    Yes, Thanks Susan. That was interesting.

    And thank you for your thoughts, Rich.

    [This Message was Edited on 06/19/2008]