=============================================================== == == == ----------- ALS Interest Group ----------- == == ALS Digest #841 (20 April 2001) == == == == ------ Amyotrophic Lateral Sclerosis (ALS) == == ------ Motor Neurone Disease (MND) == == ------ Lou Gehrig's disease == == ------ maladie de Charcot == == == == This e-mail list has been set up to serve the world-wide == == ALS community. That is, ALS patients, ALS researchers, == == ALS support/discussion groups, ALS clinics, etc. Others == == are welcome (and invited) to join. The ALS Digest is == == published (approximately) weekly. Currently there are == == 4700+ subscribers in 70+ countries. Please be advised, == == the editor is not a medical doctor and the Digest is == == not peer reviewed. This newsletter is not intended to == == provide medical advice on individual health matters. == == Any such advice should be obtained personally from a == == physician. == == To subscribe, to unsubscribe, to contribute notes, == == etc. to ALS Digest, please send e-mail to: == == bro@met.fsu.edu (Bob Broedel) == == == == Bob Broedel; P.O. Box 20049; Tallahassee, FL 32316 USA == =============================================================== == Back issues of the ALS Digest are available on-line at: == == http://www.glnicholas.com/ == == http://www.alslinks.com == == http://www.alssurvivalguide.com == == http://cc4144-a.ensch1.ov.nl.home.com/~digest == == http://health.oldeman.net == =============================================================== CONTENTS OF THIS ISSUE: 1 .. New Hope for Lou Gehrig's sufferers 2 .. ALS Support Group Meeting in Canton, Ohio 3 .. Cultured glial cells 4 .. IV Gammaglobulin treatment info required 5 .. Use of Celebrex in ALS 6 .. New York "Walks to D'Feet ALS!" 7 .. re: mercury and neurons (ALSD 828) 8 .. re: communications help needed (ALSD832) 9 .. ALS Society Strategic Plan (1) ===== New hope for Lou Gehrig's sufferers ========== Date : Fri, 20 Apr 2001 >From : Will Hubben Subject: ALS Mouse experiment shows enzyme inhibitor protects neurons New hope for Lou Gehrig's sufferers Mouse experiment shows enzyme inhibitor protects neurons ASSOCIATED PRESS April 13 - Scientists have used a chemical to delay the onset of Lou Gehrig's disease in mice and prolong their lives by blocking an enzyme crucial for cell death - a finding that holds promise not just for deadly Lou Gehrig's disease but for other degenerative nerve disorders that afflict millions. THE HARVARD Medical School research may boost efforts already under way by half a dozen drug companies to create so-called "caspase inhibitors" safe enough to test in people suffering a variety of brain diseases. The new findings "provide a compelling argument ... for the value of caspase inhibitors," Mark Gurney of the Pharmacia Corp., one drugmaker pursuing the compounds, wrote in a review accompanying the research in Friday's edition of the journal Science. "The idea is very worthwhile, no question about it," added Cornell University neurologist Dr. Flint Beal, although he cautioned that human testing is not yet planned. Some 30,000 Americans have Lou Gehrig's disease, also known as amyotrophic lateral sclerosis or ALS. No one knows the cause, but it results in a creeping paralysis as neurons, or nerve cells, in the brain and spinal cord that control movement are progressively destroyed. On average, patients die within five years of the first symptoms, as paralysis leaves them unable to eat or breathe. ENZYME TIED TO OTHER BRAIN DISEASES Caspases are enzymes that signal a damaged or worn out cell to commit suicide. Scientists now believe that in a variety of brain diseases - from ALS and Alzheimer's to Parkinson's disease and strokes - caspases that should be lying dormant inside fairly healthy neurons are instead activated to kill them. If doctors could block the caspases' action, they might be able to save important nerve cells. "That's one of the things I find most exciting," said Dr. Robert Friedlander of Harvard and Brigham and Women's Hospital, who conducted the new ALS research. "A drug that's going to work for one of these diseases is likely going to work" for several. Friedlander tested mice that were genetically engineered to get the human version of ALS. He implanted miniature pumps in their brains to bathe neurons with an experimental caspase-inhibiting chemical called zVAD-fmk. The treated mice showed ALS symptoms 20 days later than untreated mice - a long time in a mouse's lifespan - and they lived 22 percent longer, he reports in Science. If humans had a similar result, that would equal another 14 months of life, said Dr. Leon Charash, medical adviser to the Muscular Dystrophy Association, which helped fund Friedlander's work. In contrast, the only ALS drug sold today prolongs survival by about three months. Equally important, Friedlander stressed, was his discovery that caspases don't just abruptly kill off a damaged cell. Instead, their activity in one cell is essentially contagious, affecting the secretion of toxic substances that make neighboring neurons too sick to work properly. PROTECTS NEURONS So while "it's not a cure," he said giving zVAD to mice very early in the disease apparently protected some neurons that caspases had just started sickening. Would it work in people? Nobody knows, but Friedlander did find in the spinal cords of ALS patients some activated caspase identical to that in sick mice, a good sign. But pharmaceutical companies are waiting for a better drug before testing it in people, said Friedlander, who found similar results a year ago when he tested a caspase-inhibiting chemical in mice with Huntington's disease, another incurable killer. He said he does want to test zVAD in people, but its maker fears it could cause serious side effects. The chemical was created solely for laboratory use, not as a potential human drug. The drug also would require direct infusion into the brain or spinal cord, "no trivial matter," Cornell's Beal cautioned. Still, he said, "This is a desperate illness" and he expects high patient demand for any caspase inhibitor that makes it to human testing. Half a dozen companies, including Pharmacia and drug giant Merck & Co., are trying to create caspase inhibitors. When asked if human tests were foreseeable within the year, Pharmacia's Gurney said not with his company's version; Merck officials didn't comment. --------------------------- Will Hubben whubben@earthlink.net (2) ===== ALS Support Group Meeting in Canton, Ohio ========== Date : 20 Apr 2001 >From : pcazzo@cswebmail.com Subject: Anyone is cordially invited to attend the ALS SUPPORT GROUP MEETING IN CANTON, OHIO SUNDAY, APRIL 22, 2001 at 2:00 PM PLACE: MERCY SURGERY CENTER 13th Street at Exit #106 on I-77 in Canton, Ohio (go east on 13th St.; turn left at first driveway entrance on the left, past the Mercy Dr. intersection; accessible parking in front of glass building; large car port, wheelchairs available and volunteers to offer assistance) TOPIC: "LIVING WITH ALS" SPECIAL GUESTS SPEAKERS: DOUG AND IRENE ESHLEMAN ** Come hear Doug Eshleman who has ALS and his wife, Irene, share their story of success and how they have lived with ALS. ** See their fantastic website: www.lougehrigsdisease.net ** Come to the meeting to become encouraged by others and to learn that you are not alone ** Time also to share your experiences ** Refreshments will be served For further information call Pamela Cazzolli RN at 330-497-1792. Program sponsored by the Muscular Dystrophy Association (3) ===== Cultured glial cells ========== Date : Thu, 19 Apr 2001 >From : Will Hubben Subject: Cultured glial cells are resistant to the effects of motor : neurone disease-associated SOD1 mutations. Cultured glial cells are resistant to the effects of motor neurone disease-associated SOD1 mutations. [Record Supplied By Publisher] Neurosci Lett 2001 Apr 20;302(2-3):146-150 (ISSN: 0304-3940) Williams RE.; Cookson MR.; Fray AE.; Manning PM.; Menzies FM.; Figlewicz DA.; Shaw PJ. Department of Neurology, The Medical School, University of Newcastle, Newcastle upon Tyne, UK. Free radical damage has been implicated in the pathophysiology of motor neurone disease (MND); mutations have been identified in the gene encoding Cu/Zn superoxide dismutase (SOD1). There is evidence that glial cell dysfunction may contribute to motor neurone injury, but the exact role of glial cells in MND has yet to be established. The aim of this study was to determine whether expression of mutant SOD1 affects the response of glia to oxidative stress. Stable C6 glioma cells expressing mutant SOD1 and cortical astrocyte cultures from G93A-SOD1 transgenic mice were exposed to: xanthine/xanthine oxidase; hydrogen peroxide; A23187 and 3-morpholinosydonimine. Cell viability was measured using the 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Neither C6 glioma cells nor cortical astrocytes expressing mutant SOD1 were more susceptible to any of the free radical generating systems compared to control cells. These results suggest that astrocytes are resistant to the toxic effects of mutant SOD1 widely reported for neuronal cells. --------------------------- Will Hubben whubben@earthlink.net (4) ===== IV Gammaglobulin treatment info required ========== >From : "narayan J" Subject: IV Gammaglobulin treatment info required Date : Thu, 19 Apr 2001 Some time back in ALS Digest #826 (26 March 2001) there was a mail by Harry Gould talking about IV Gammaglobulin treatment for ALS,GIDP & MNM. After that there hasn't been any more communication on that. A real disappointment. Has anyone been able to get more information on this? I spoke to my nuerologist & she willing to explore this area ..but we definitley need more info .. I was hoping actualy if Harry could provide some email contact of his nuerologist Dr. Moreira....Harry Gould suugests in his mail to travel to San Juan for the treatment...but basically its definitly not possible to travel to San Juan....but my nuerologist is prepared to communicate with Dr Moreira to obtain the details of the treatment...if only someone can give more information... Please do write to me if you've more info ..anyone.. thanks & regds (5) ===== Use of Celebrex in ALS ========== Date : Mon, 16 Apr 2001 >From : Will Hubben Subject: USE OF CELEBREX IN ALS >From Kyle Hahn: USE OF CELEBREX IN ALS Dr. Jeffrey Rothstein is prescribing Celebrex for his ALS patients Cyclooxygenase-2 Inhibitor Protective in ALS Model WESTPORT, CT (Reuters Health) Nov 27 - Selective cyclooxygenase-2 (COX-2) inhibition protects against motor neuron loss in an in vitro model of amyotrophic lateral sclerosis (ALS), according to a report in the November Annals of Neurology. Glutamate accumulation in the synaptic space produces neurotoxic effects, and astrocytes can release glutamate in response to prostaglandins and other triggers, the authors explain. By powerfully inhibiting astrocytic glutamate release, they say, COX-2 inhibitors might play a therapeutic role in ALS. Accordingly, Dr. Daniel B. Drachman and Dr. Jeffrey D. Rothstein from The Johns Hopkins School of Medicine in Baltimore, Maryland, tested the effects of a selective COX-2 inhibitor, SC236, in THA-treated spinal cord cultures. THA inhibits the astroglial transport of glutamate and thereby induces gradual loss of motor neurons as seen in ALS. Highly significant loss of motor neurons in untreated cultures occurred within 3 to 5 weeks after the addition of THA, the report indicates. In contrast, SC236 potently and significantly protected against motor neuron damage at all concentrations tested, the authors report. "Our findings show that COX-2 inhibition had a highly significant protective effect on motor neurons in this model system,"the authors conclude. "COX-2 inhibition could have therapeutic effects in ALS by altering the cascade of pathogenic processes that otherwise cause relentless progression of motor neuron damage," Drs. Drachman and Rothstein add. ************************************************************** 1: Ann Neurol 2000 Nov;48(5):792-5 Inhibition of cyclooxygenase-2 protects motor neurons in an organotypic model of amyotrophic lateral sclerosis. Drachman DB, Rothstein JD Department of Neurology, The Johns Hopkins School of Medicine, Baltimore, MD 21287-7519, USA. [Medline record in process] The pathogenesis of motor neuron loss in amyotrophic lateral sclerosis (ALS) is thought to involve both glutamate-mediated excitotoxicity and oxidative damage due to the accumulation of free radicals and other toxic molecules. Cyclooxygenase-2 (COX-2) may play a key role in these processes by producing prostaglandins, which trigger astrocytic glutamate release, and by inducing free radical formation. We tested the effects of COX-2 inhibition in an organotypic spinal cord culture model of ALS. The COX-2 inhibitor (SC236) provided significant protection against loss of spinal motor neurons in this system, suggesting that it may be useful in the treatment of ALS. PMID: 11079544, UI: 20529928 --------------------------- Will Hubben whubben@earthlink.net (6) ===== New York "Walks to D'Feet ALS!" ========== >From : "Kathie Speer" Subject: New York "Walks to D'Feet ALS!" Date : Tue, 17 Apr 2001 New York "Walks to D'Feet ALS!" Let's get organized NOW for the ALS Association Greater N.Y./Northern N.J. Chapter's "Walks to D'Feet ALS!" We need YOU--volunteers, team leaders (and we'd love sponsors). Take a giant step for ALS research and patient services. Join us for our 3.1 mile walks at Jones Beach State Park, Long Island, Sunday, Sept. 30th and Liberty State Park, Jersey City, NJ, Sunday, Oct. 21st. Call Lisa at 212-619-1400 TODAY for details. It's not too early! (7) ===== re: mercury and neurons (ALSD 828) ========== >From : Bernie Windham Subject: Re: ALS Digest 828 Mercury and Neurons Date : Mon, 2 Apr 2001 >Jim Duke jduke@onlinemac.com wrote: >The post by Mr. Windham is incorrect. At no time is ALS linked with >mercury in this article, in fact, the term ALS is not utilized in the >journal article. The article clearly demonstrated that neural growth >in snails could be inhibited with exposure to mecury but lead and other >metals had no apparent effect. The article in question is only one of about 50 articles that I referenced in my paper that documents that mercury accumulates in the motor neurons and causes the types of damage to neurons found in Alzheimer's and ALS. I and the author and other reviewers think the this paper is obviously relevant to ALS and other degenerative neurological conditions, as well as Alzheimer's neural degeneration. The study showed that mercury at very low levels, levels found in those with amalgam, destroys the growth cones in nerves, resulting in major damage or destruction to large numbers of neurons. I have the entire paper so am aware of what it says. I also think the relevance is pretty clear. So do most researchers I'm aware of who've looked at the studies. But you overgeneralize on the question of the other metals as well as the relevance of this article to ALS imo. The other metals are documented to have major neurological effects in lots of other studies. Just not the specific and catastropic effect that mercury has that was dealt with in this study. People can decide for themselves if the study is relevant to ALS since I gave info on how to access it, and also whether the full documentation of about 50 medical studies that make the case that mercury causes the type of damage seen in ALS makes a strong case. Full papers can be obtained from Medline in most cases(www.nlm.nih.gov). My paper that has been posted before is at www.home.earthlink.net/~berniew1/als.html More supportive research from ALS researchers can be found at the Medical lab sites: www.altcorp.com and www.melisa.org (who also think this study is relevant) B. Windham (8) ===== re: communications help needed (ALSD832) ========== >From : TWERDEL@aol.com Date : Fri, 6 Apr 2001 Subject: Re: Betsy, L.C. Technologies, Inc. has an excellent "Eyegaze" system which my wife has been using for about one year. Contact: Nancy Cleveland at 703-385-7133. Tom Werdel (9) ===== ALS Society Strategic Plan ========== >From : "Susan" Subject: ALS Society Strategic Plan Date : Wed, 11 Apr 2001 Colleagues, Our attempt to use an e-group source to invite contributions to the ALS Society of Canada strategic planning process has proved complex and frustrating. (If you have forwarded a response to me directly, please disregard this message.) Nevertheless, we are VERY interested in receiving your comments on three questions. We have returned to a simpler method! Please take 20 minutes to think about and respond to the following address - jh@als.ca A prompt reply would be appreciated. Your contributions will help our organization develop further. If you know of others who might want to make a contribution to this process please don't hesitate to forward this message. All those responding will receive updates on the process, including a compilation of responses to these questions. I look forward to hearing from you! Jonathan Current Mission of ALS Canada: To Provide Care and Find a Cure for ALS 1. What are your aspirations and hopes for the ALS Society of Canada over the next 2-3 years? Where do we want ALS Canada to be in three years? 2. What are 2-3 measurable goals against which the achievement of these aspirations and hopes could be judged? 3. What are the 3-5 most important things that have to occur so that these measurable goals can be met and the aspirations achieved? Jonathan Harris Past-President ALS Society of Canada jh@als.ca 800-267-4257 416-497-1256 fax 416-497-2267 alscanada@als.ca www.als.ca 265 Yorkland Blvd., Suite 300, Toronto, Ontario M2J 1S5 === end of alsd 841 ===