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insecticides, nerve gas and statin drugs and PON

eml256
0 Recommendations

Northwestern University
Variations in detoxifying genes linked to Lou Gehrig's disease
Genetic variations in three enzymes that detoxify insecticides and
nerve gas agents as well as metabolize cholesterol-lowering statin
drugs may be a risk factor for developing sporadic amyotrophic lateral
sclerosis (ALS, or Lou Gehrig's disease), and possibly responsible for
a reported twofold increased risk of ALS in Gulf War veterans.
These findings, from a study led Teepu Siddique, M.D., and colleagues
at Northwestern University, open the door to investigating
gene-environment interactions as a cause of ALS and other illnesses and
to the development of molecular targets for specific treatments. The
study was published in the August 22 online issue (available now) of
the journal Neurology. (http://www.eurekalert.org/pub_releas...-vid070506.php )

Explore topics in this discussion:

High cholesterol Surgery Lipitor Amyotrophic lateral sclerosis (ALS) Riluzole Zocor Parkinson's disease Stress Asthma Heart disease Tricor Hospice care Stroke Viagra Foot drop Hypertension Alzheimer's disease ALS Heart attack

30 replies

KimHymes

The following overview was developed by the Research Department at The ALS Association.

What is the Link Between Statin Drugs and ALS?

A possible link between use of the drugs called statins that help to lower cholesterol, and ALS, is the subject of media attention lately. The link is not a proven cause and effect relationship, merely a possibility raised by an investigator who has published statistics showing more than the expected number of cases of an illness similar to ALS among statin users. He states that this is not a demonstration of whether or why ALS could be produced by statin use but raises caution to monitor for a possible link.

Dr. Ralph Edwards, Director of the World Health Organization drug monitoring center in Sweden, and colleagues, published in the Drug Safety journal that of the 172 people in the database who developed ALS-like disease, 40 could be confirmed as taking statin drugs. These data however do not prove cause. Edwards states himself in his paper "We emphasize the rarity of this possible association, and also the need for further study to establish whether a causal relationship exists".

In fact this is the kind of question that highlights the need for a registry of ALS patients in the United States, an effort gaining success through the advocacy efforts of The ALS Association. Currently, 268 Representatives and 41 Senators are cosponsoring the ALS Registry Act, legislation which promotes a better understanding of the disease, help to determine causes of ALS and significantly enhance the nation’s efforts to find a treatment and cure for ALS.

Click here to urge your Representative and Senators to support the ALS Registry Act!

Statin Use Common; ALS Rare

Statin use is common: these widely prescribed drugs can help people lower the level of cholesterol and therefore the risk of heart and blood vessel disease. Many millions of people worldwide have used statins safely for many years.

ALS is rare. About 30,000 people are living with ALS in the United States. Since so many people take statins, it is not surprising that a few will be taking these drugs at the time that they develop ALS. However, the caution raised the recent published report is that more than the expected number of instances of ALS-like symptoms appeared in an international drug safety monitoring database, which included people using the statin drugs.

Most ALS patients have not used statins and of course the disease existed long before statins were introduced into medical practice in the past two decades. No rise in incidence of ALS has occurred during this time, and no direct cause can yet be attributed to statin use for ALS.

No biological explanation can yet be offered for why statins might produce ALS.
Scientists still do not know the direct cause of ALS. Both genetic characteristics and environmental exposures may interact to contribute to the disease.

Ask Your Doctor

In the past physicians noticed that a very few people using statins developed a type of muscle disorder, not related to ALS. This rare side effect of statin use is well known and a caution is already included in the labeling of the drugs. Physicians monitor patients taking statins to be sure they do not show evidence of this rare effect. ALS-like symptoms are different from this muscle damage.

The use of statins should be discussed with a neurologist. Clinicians are preparing to focus attention on the issue of statin use and ALS at the upcoming 18th ALS-MND Symposium in Toronto in December.

  • More information about ALS Research

    • timecard

    my h usband- ROBERT C. WARREN, was dxX on march 2, 2006 and passed away july 2, 2006. . he served in the navy from 1968-1970.his last duty was on the -dmz-in seoul, korea. his doctors told him to apply for-va-benefits as this disease is service connected. he applied but, -va -said they never received his application. and he got to sick so fast we could not get an appointment with the va doctors. NOW I HAVE BEEN TOLD TO APPLY FOR-BURIAL BENEIFITS AND DIC. I PROBABLY WILL BE DENIED-BECAUSE I CAN'T PROVE THAT HIS DISEASE WAS SERVICE CONNECTED. BUT, VA-CAN'T PROVED THAT IT WAS NOT.
    I NEED HELP-DO YOU KNOW ANYONE IN THIS SITUATION OR WHO I COULD CONTACT. I AM DISABLED MY SELF AND NEED THIS HELP.
    THANK YOU
    mary frances warren
    belzoni, ms.E-MAIL-cam@belzonicable.com

    msgar1ginny

    Cale had been on Zorcor for at least 5 yrs before dx. He also had a knee replacement 2 yrs before dx and back surgery 1 yr before dx. Also he had fought in the Korean War and been exposed to a lot of chemicals. I do not know what if any of these things caused it or triggered onset of ALS but we just have to find a cure. Too many wonderful people are losing their lives to this terrible disease.

    Oldchuck

    JJ,

    Thanks for asking. Actually I am in one drug trial and it is for emotional lability or the tendency that some of us have to laugh and cry excessively when triggered by even slightly funny or sad occasions. The trial drug was to be marketed under the name Nuerodex but I think the company has changed the name and the FDA has held up its release pending additional data. It is a combination of two known drugs, quinidine and a compound found in most cough suppressants, dextramorphan (sp?). It is an open trial, meaning that all participants get the drug. It is administered in my location by the Neurology Department of the Suncoast Medical Clinic in St. Petersburg, FL, and the trial investigator is Dr. Alberto Vasquez. I am not sure if they are still enrolling because the drug is near FDA approval for widespread use. I am on my second year in the trial and have had no adverse side effects, and my wife says she notices some improvement.

    The second is not really a trial but more an experiment. I do not get any medication. I merely provide the investigators at the University of South Florida Medical School with periodic blood samples, about every six months at which time their neurologist does an examination to determine the level of progression of ALS. They are still looking for ALS patients to enroll. The contact for this trial is : Svitlana N Garbuzova-Davis , It is being done under the auspices of a drug company that is investigating the use of umbilical stem cells to determine biomarkers in the blood of ALS patients and with that information, targetting treatments to those biomarkers. At least that is my simple understanding of the trial. I have seen some reports on the project in the open literature that is encouraging.

    Ole Chuckles

    JJ3

    Ole Chuckles,

    IN your comment on PONS, you mentioned that you are participating in 2 trials. Would you elaborate on that. Are you taking 2 drugs in the same trial or is it 2 separate trials? There is currently no trial open within driving distance to me. Actually there is one, but it is too invasive and involves leaving a "port" open in a vein. I'm not ready for that yet. If you are in 2 separate trials, how will you know which drug helps, causes side effects, etc. Your comments have been very helpful on other topics. Thanks for being a positive "force". JJ

    pjf

    Hi,
    I read with interest of the San Diego State questionnaire. The only thing we can think of that could have caused ALS for my husband is cholesterol statin drugs. He was on four in succession and lost 35# in that period of time . Dx with ALS six months later (july 06) at the Mayo Clinic. Will you please publish the address or whatever so that we can participate?
    I registered so that I could communicate with you. The daily hot line is so informative and it's great of all of you to be so open with information.

    Memaw2

    Jimmie,
    I have been told that Hospice will take you if you ALREADY have the wheelchair, vent, BiPap or whatever. You can't get it after you go on Hospice according to Medicare rules. Check it out.

    Memaw2

    I have taken Zocor for about 6 years and was dx. last year. Symptoms began about a year after beginning Zocor but were vague.
    I developed foot drop in March 2005.

    Jimmie_M

    I agree 100% with what Old chuck has to say about this. My wife was diagnosed on 11 Aug 2006 and now resides in a nursing home ? WHY ???? Because I work full time, can not afford to pay 10 to 20 dollars per hour for care. She does not get access computers, speaking devices, power chairs or anything that I read about that people use that have this disease. I think most times that know one cares and I think it will be hard to turn that around.
    I my short walk with this disease I have been mislead, lied to and basically told why fight, there is nothing we can do or that you can do. Well as my wife is vented and trached and wants to live, I can and will fight to change things. I have made well over 500 phone calls and the only thing that offers any hope is full time hospice care, and there again the Medicare rules state no speaking device or power chair, as if they want her to come home and lay in bed and stare at the ceiling.
    Our government and law makers have no care or compaasion, and you can bet when they are flying to the Bahama's or a suuny coast at a drug makers expense Als is not on their radar screen.
    I compare this to Hiv which is casued by sin and lust and is a bilion upon billion dollar drug bonanza and Als is not nor do I wish it to be.
    The point is Hiv was and is fatal, but the average life expentency is now 25 years for an HIV patient. We all remeber the headlines and all the scares and such,. Well folks, big Pharamcia is why. They have no conviction or care in our plight.
    A national rally would help, but we all know that many can not attend, physical or finical or whatver reasons.
    Post like this on the net get us fired up, but we need a 1 month or year long image on 60 minutes, 20/20 or the today show. Showing people Cals and Plas and bringing national attention to this delima.
    I also would like to see "Care" home for Als only patients - vents , trachs, chairs and skilled staff and access to supplements and water therpy access. If we could get something like this launched with 1 per state with a 50 patient or so load, things would be better for many pals and cals.

    Remeber always with God anything is possible.

    eml256

    i posted about PON gene cluster polymorphisms because I think it an important piece of information for individuals who suffer from neurodegenerative diseases--and the follow up media clip about a study looking at a link between parkinon's and statins. i too think most physicians are hard working, caring, dedicated individuals who go to work every day to deliver the best care they can give. reading the statin studies published in peer reviewed, legitimate medical journals, anyone would think they were the best thing discovered since insulin--actually, I have seen that comparison made. and remember that heart disease is still the # 1 killer in the US. However, once a drug gets into the general population--and goodness knows statins are in the general population--the real adverse effects start appearing--and now they can be reported via the internet, which i think is a wonderful thing. until the FDA reports the side effects or until a study on statins uncover the side effects and reports them, scientists and physicians do not believe they exist. pharmaceutical cos do not want to conduct studies that will uncover some dire adverse effect of its drug--esp a powerhouse like statins (lipitor made Pfizer $14 Billion last year alone), so those studies are not conducted and are not mandated by the FDA. physicians DO NOT make any $$ from prescribng a specific drug--physicians believe the drug prescribed is the correct drug for the correct ailment--and yes, we live in such a litigious society that given the press about statins, the responder who commented about treating a patient's high cholesterol according to the Heart Health guidelines or possibly facing litigation, is correct. and I have never seen a physician who is happy to talk with a pharm rep--they frequently have office staff talk to them and obtain free samples which they give to their patients (my neighbor who is 93 yrs old receives her anti hypertension drugs free from her cardiologist because he knows she lives on a fixed income.)
    the products from pharmaceutical cos have multiplied incredibly within the past 10 yrs--it does not hurt to stay abreast of your meds and/or the effect upon whatever disease you suffer....i specifically posted under the "military" topic because of the association btn PON genes and detoxification of organophosphates and sarin gas....never thinking it would be statins that received the most attention--though guess i should have given the #'s of people on statins today.

    TracyBengtson

    My dad started having ALS symptoms also right after taking Zocor. He wasn't on it very long. At first he thought his symptoms were a reaction or side effect, as noted in the fact sheet with the medication. He didn't even really need it because he always had low cholesterol.
    Tracy, daughter of PALS

    teriqueen

    Don't get me wrong, I agree that Doctors are very important to our well being and what would we do without them. I just don't think that all the drugs that are advertised are all that good for you. Just look at all the warning signs they give you. The side effects that make it seem that it's better to deal with the orginal problem. Who wants all those possible side effects? I know that Doctors are just doing their jobs but they need to be sure that the patient understands the possible side effects. Most doctors aren't even aware themselves because what doctor has time to study every drugs side effects. Maybe we as patients need to ask our doctors more questions about the drugs they are giving us? Who's responsibility is it.? How do we know that Statin drugs aren't the cause of some diseases?

    For me, I would just like to know more about these drugs and how many others could be affected by them. I know we can't blame anyone or anything for our loved ones getting ALS but wouldn't it be better to know that if a certain drug could be the cause that we make sure that it doesn't harm anyone else?

    Sorry, I'll get off my soap box now. I just don't think that Statin drugs are the only answer to lower cholesterol.

    Teriqueen

    Bernadette2

    I don't mean to be dismissive regarding the concerns expressed here about statin drugs. Researchers very well may find out that these drugs are a trigger for neurological disease. But I would like to stick up for the traditional medical profession for just a minute here. I honestly believe that most physicians are decent people who want to see their patients get better. It makes sense to me that they prescribe these cholesterol-lowering drugs for their patients. What would anybody do in their shoes? A patient goes to see his doctor, his cholesterol is off the chart, a drug is available that lowers cholesterol. Said patient has heard about the drug from his brother, people at work, and Aunt Mary, all of whom are telling him that he too should be taking this "wonder drug" to lower his cholesterol. What should the physician do--tell the patient he doesn't need the drug, or that maybe the drug will cause him problems in the future, or that maybe he should try garlic instead?

    Also, like anybody else, physicians want to continue working in their jobs of choice.One of the reasons doctors prescribe drugs that lower cholesterol for patients with high cholesterol is because of our litigious society--because of our knee-jerk reaction to take somebody to court, to blame anybody or everybody for the bad things that happen in life. If Harold goes to his doctor with sky-high cholesterol and his physician doesn't prescribe the drug and Harold dies of a heart attack, what's the most likely thing that's going to happen? Harold's family is going to scream bloody murder in court: "Why didn't you prescribe Vitorin for our dear old Harold?"

    Personally, I thank my lucky stars that I went to nursing school instead of medical school 30-odd years ago, since I was able to walk away from the nursing profession after 20 years a lot easier than I could have walked away from being a physician. I know from experience that sometimes working in the medical field can be a thankless job, so therefore I thank God that there are good people who continue, even in these suit-happy times, to work in the medical profession. Are doctors perfect? Of course not. Is the system perfect? Heck no. But consider just for a minute a world without them.

    My rant for the day.

    Bernadette

    Thomas2

    Ann,

    My husband started having symptoms after he started "Lipitor". I still believe this was what triggered ALS, in his case. He only took it for 2-3 months, but everything started happening right after. CALS Janet

    Eddiespaza

    Dear Ann,

    I'm so glad that you brought this up. Now that I have had to go on a disability retirement from my job, I have had a lot of time to review/ponder/wonder what it is that I did in my life that could have possibly triggered my diagnosis of ALS. About two years before my diagnosis by Dr. prescribed a Statin drug called Tricor after getting my DX. I went backwards and reviewed any and all lifestyle changes that preceded my diagnosis. I got on a web site that was called Worst Drugs.com -- and found Tricor amongst the worst. I have always wondered if any of the drugs that I was taking. Previous to my diagnosis were the trigger for my ALS. Two years previous to my ALS diagnosis. I was taking, Tricor and Viagra -- the only other thing that might have affected my health. Is that I was working at very high stress job -- and I have often wondered if the high stress could have been the trigger.

    Eddie spaghetti

    CherylW

    Terrqueen,

    Definitely will check out site. I want to get as much information and give as much information as I can regarding my husband's situation. Never knew of the link with statin drugs until I got involved on this site. It's a great place for informative information.

    Thank you for sending me the info.

    Oldchuck

    Wow, now I think I know what PON is or are or may be. Unless and until there is more comprehensive and detailed histories of working and living environments associated with PALS it seems to me that little in the way of valid epedemiology can be done and I don't see any of the current data bases collecting this type data or information. I have filled out more questionaires than I care to mention as I trundled from neurologist to neurologist seeking a diagnosis and I have been associated with two ALS specialty clinics and am participating in two trials. In no case has this type of information been gathered. I have the feeling that the realities of PALS full history are not being studied and, perhaps this is the reason that we continue to research so many different avenues with little real results that impact on those of us who are dying. Realistically, I want to see the incremental therapies developed to address the HIV/AIDS crisis that led to combined therapies that are allowing AIDS to be treated as a chronic illness rather than a terminal illness. I see none of this in the ALS arena. I see a lot of mention of a cure but darned little about finding a rapid confirmatory diagnostic test or interim life extending therapies. Tell me I am wrong, but in the past two years when I have spent many hours educating myself on this disease I have, I find little to give me hope that these new interim therapies are anywhere close to helping us. I find this disturbing and perhaps symptomatic of a system that has lost what I call patient centricity. Process rather than patient seems to be the focus.

    Sometimes we let research become the end all rather than the means to finding a solution. Raising funds for research and competing for these funds can become the name of the game rather than seeking incremental therapies to add to the meager relief now offered by riluzole.

    Anyway, thanks for telling us what PON is. Now go back and find me something to extend the quality and duration of my life.

    If I sound a little testy, I mean to. I watched a compelling movie on TV yesterday about the struggles of Jennifer Estess. I am struck by the same level of systemic ignorance by the general and specialty medical profession on ALS, its diagnosis and subsequent care. I am similarly struck by the fact that little real progress has reached us since the film was made or Jennifer's life dwindled away. I find that frustrating when viewed against the huge amounts of funds raised and directed to research, and the bureaucracies of the myriad of organizations and foundations and institutions that gave grown up, sucking up a good deal the funds that might be use more fruitfully to address patient and family care. I see major advances in the scope and availability of durable medical equipment to provide improved quality of life, but when I look at the prices that this market has generated and is being sucked from the Medicare, Medicaid and insurance resources it seems that a similar model needs to be developed for identifying and implementing therapeutic advances and solutions.

    Amen.

    Ole Chuckles

    teriqueen

    So it looks to me like more and more of you have had experience with the Statin Drugs.

    Here is the website to go to for the Statin Drug Study:

    statinstudy@ucsd.edu

    Please go there because if we get enough of you to participate we might be able to make a difference.
    I would love to see this poison banned forever. There are natural ways to lower your cholesterol but doctors don't want you to know about it because then they don't get a perk for perscribing it to you.

    Teriqueen

    CherylW

    My husband, Harry, was on several cholesterol drugs. Every time, he tried one after a short time on it, he would complain of what he thought was his tongue swelling and than he would have problems speaking and being understood. He would stop the drug and it would seem to clear up a little and he would try another one. After the last drug, his heart doctor decided no more. However, the last time we saw no improvement in his speech. About 7 months later, he was diagnosed with ALS. I am definitely going to look into this further.

    eml256

    I am so sorry for leaving a partial explanation of what PON is--I had never heard of PON either until I began researching statins and Parkinson's...

    http://www.northwestern.edu/newscenter/stories/2006/07/paraoxanase.htm l
    The genes for human paraoxanases (PON 1, PON 2 and PON 3), which are located on chromosome 7q21.3, code for the production of detoxifying enzymes involved in the metabolism of a variety of drugs, organophosphate insecticides, such as parathion, diazinon and chlorpyrifos, and nerve gas agents such as sarin.

    Previous research described a possible twofold increased risk for developing ALS in veterans of the Gulf War, indicating a war-related environmental exposure to organophosphates and sarin in genetically susceptible individuals as a possible cause.

    PON gene cluster variants have previously been associated with other neurodegenerative and vascular disorders, including Alzheimer's disease, Parkinson's disease, coronary artery disease and stroke.

    Although the Northwestern DNA study samples were not analyzed for inclusion of Gulf War veterans, Siddique and co-researchers found significant evidence that gene variations (polymorphisms) on the chromosome region encompassing PON2-PON3 were strongly associated with sporadic ALS.

    “Thus, single nucleotide polymorphism genotyping in the intergenic regions of the PON gene cluster, and replication, gene expression, gene-gene interaction and PON serum/enzymatic studies may help elucidate the complexity of PON cluster association with ALS,” Siddique said.

    Siddique hopes to study DNA samples from Gulf War veterans with increased incidence of sporadic ALS and has applied for their DNA from the Veterans Administration collection.

    Collaborating with Siddique on this research were Mohammad Saeed, M.D.; Nailah Siddique; Wu-Yen Hung; Elena Usacheva; Erdong Liu, M.D.; Robert L. Sufit, M.D.; Scott L. Heller, M.D., Northwestern University Feinberg School of Medicine; Jonathan L. Haines, Vanderbilt University Medical Center; and Margaret Pericak-Vance, Duke University Medical Center.

    This study was supported by grants from the National Institute of Neurological Disorders and Stroke; Les Turner ALS Foundation; V. E. Schaff ALS Research Trust; Wenske Foundation; Harold Post Professorship; Les Turner ALS Foundation/Herbert C. Wenske Foundation Professorship; Falk Foundation Fund; and The David C. Asselin M.D., Memorial Fund.

    a bit more info on PON gene clusters:
    http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&l ist_uids=16319130&dopt=Abstract

    Polymorphisms in the PON gene cluster are associated with Alzheimer disease.Erlich PM, Lunetta KL, Cupples LA, Huyck M, Green RC, Baldwin CT, Farrer LA; MIRAGE Study Group.
    Department of Medicine (Genetics Program), Boston University School of Medicine, Boston, MA 02118, USA.

    Paraoxonase is an arylesterase enzyme that is expressed in the liver and found in the circulation in association with apoA1 and the high-density lipoprotein, and prevents the accumulation of oxidized lipids in low-density lipoproteins in vitro. Common polymorphisms in genes encoding paraoxonase are established risk factors in a variety of vascular disorders including coronary artery disease and carotid artery stenosis, but their association with Alzheimer disease (AD) is controversial.

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