Date: Wed, 2 Nov 94 15:28:09 EST From: Bob Broedel To: Stuart.Neilson@brunel.ac.uk Subject: Re: ALS Interest Group List =============================================================== == == == ----------- ALS Interest Group ----------- == == ALS Digest (#132, 07 October 1994) == == == == ------ Amyotrophic Lateral Sclerosis (ALS) == == ------ Motor Neurone Disease (MND) == == ------ Lou Gehrig's disease == == ----- == == 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 == == 360+ subscribers. == == == == To subscribe, to unsubscribe, to contribute notes, == == etc. to ALS Digest, please send e-mail to: == == bro@huey.met.fsu.edu (Bob Broedel) == == Sorry, but this is *not* a LISTSERV setup. == == == == Bob Broedel; P.O. Box 20049; Tallahassee, FL 32316 USA == =============================================================== CONTENTS OF THIS ISSUE: 1 .. methylsulfonylmethane 2 .. Morse Code 3 .. Looking for info. about Brain Stem Evoked Potentials 4 .. MDA Research Report #52 (1) ===== methylsulfonylmethane (MSM) ========== Date : Thu, 6 Oct 1994 22:49:07 -0500 (CDT) >From : Clive David Subject: methylsulfonylmethane (MSM) Does anyone have experience or knowledge concerning the therapeutic (and side) effects of a supplement called methylsulfonylmethane (MSM)? A colleague of mine swears by MSM's effectiveness in improving inflammatory and arthritic conditions. It has also been reported as improving autoimmune disorders. The physiological effect is apparently tied to sulfur nutrition ... Thanks, and best wishes. ============================ |Clive David | |E-mail: cdavid@worf.uwsp.edu| ============================ (2) ===== Morse Code ========== >From : stuart@onyx.bc.ca (Stuart Lory) Subject: contribution Date : Thu, 6 Oct 1994 19:31:33 -0700 (PDT) I wish to add the following contribution to the ALS digest on behalf of the Victoria chapter of the ALS society. It is as follows: Thank you for the ALS digest re summary of voice synthesizers. I would like to advise readers of a procedure we intend to implement this month in our chapter. Since one of the last failures of an ALSer is his eye lids, I propose that soon after onset of the disease the patient and primary care giver (plus any other friends or relatives interested) should learn Morse Code. When digital function is still available, tapping messages is possible. In the last resort the blinking eyes will suffice. I have access to retired Navy "Sparkers" to teach our patients. Semaphore using fingers only is also possible and easier to learn! I will keep you posted on our progress. - .... .- -. -.- ... Phil Bissell President, Victoria Chapter ALS Society of British Columbia -- Stuart Lory slory@access.victoria.bc.ca Victoria, British Columbia, Canada (3) ===== Looking for info. about Brain Stem Evoked Potentials ========== >From : "LARIOS ROSILLO VICTOR MANUEL" Date : Thu, 6 Oct 1994 13:29:25 CST Subject: Looking for info. about Brain Stem Evoked Potentials Hi, we are working in the research of Brain Stem Evoked Potentials (BSEP) and if its possible that you could help us with information about the specifications and electrical characteristics of equipment to generate visual, auditive and somatic sensorial stimulus with BSEP or if you know other person, Institute or any other resource of information about BSEP. If you know something you can answer to the next e-mail adresses listed below. a17013@itesocci.gdl.iteso.mx a17625@itesocci.gdl.iteso.mx a16813@itesocci.gdl.iteso.mx We apreciate in advance your coperation and useful help to us, sincerely yours Victor M. Larios Efrain Sanchez L. Juan Antonio Vargas Instituto de Investigaciones en Neuroplasticidad y Desarrollo Celular (IINEDEC). (4) ===== MDA Research Report #52 ========== Date : 07 Oct 94 00:48:15 EDT >From : Barry Goldberg <71154.330@compuserve.com> Subject: MDA Research Report #52 Now THIS one is on time! For September do you believe! MDA Working Groups MDA has established a Familial Amyotrophic Lateral Sclerosis (FALS) Therapeutics Working Group for the purpose of facilitating research utilizing the FALS transgenic mouse model. MDA- supported researcher Mark Gurney, Ph.D., of Northwestern University Medical School developed the mouse model containing a defective version of the SOD1 gene. The animals have a motor neuron disorder with effects that are similar to the disease seen in humans. Additional mouse models that have different SOD1 gene defects may soon be available. The FALS Therapeutics Working Group will be composed of academia- and industry-based researchers who are working on projects to evaluate possible therapeutic compounds or who are studying the mechanisms behind this particular form of FALS. The mouse model that was developed with MDA support will play a key role in the research and, therefore, it will be made available for use by the scientific community. By establishing an environment to encourage collaboration among FALS/SOD1 researchers, MDA hopes to enhance the progress of work in this area, which should have an impact on our understanding of all forms of ALS. Research Papers Developing motor neurons are stimulated and protected by nerve growth factors such as ciliary neurotrophic factor (CNTF) and brain-derived neurotrophic factor (BDNF). Alone, CNTF and BDNF have been shown to slow the progression of motor neuron disease in wobbler mice -- a model of motor neuron disease that may relate to ALS and SMA in humans. The effects of CNTF and BDNF when given together have been recently studied using the wobbler mouse model, and it appears that the combination of the two factors provides more benefit than either factor alone. The researchers observed that the severe motor dysfunction in the wobbler mouse had been halted. (Mitsumoto, H. et al. Science 1994; 265:1107-1110). Adhalin, the 50kD dystrophin-associated glycoprotein, is reduced in the skeletal muscle of individuals with severe childhood autosomal recessive muscular dystrophy (SCARMD). The disease has been associated with a defective gene located on chromosome 13, however, this did not apply to all affected families. MDA researchers recently showed that the adhalin gene, which is located on chromosome 17, is defective in a family affected by SCARMD and genetic information resulting from their study is now available for the analysis of other families. Many forms of autosomal recessive muscular dystrophy can be quite similar clinically and the diseases will have to be distinguished genetically as they may be caused by defects in different genes. (Roberds, S.L. et al. Cell 1994; 78:625-633). In myasthenia gravis (MG) the autoimmune response to the acetylcholine receptor (AChR) causes difficulties in the transmission of signals between nerve and muscle that result in muscle weakness. The abnormal immune system mechanisms that create these problems have been studied extensively and appear to involve antibodies as well as other factors such as T cells. Recently, researchers blocked the response from the immune system's T cells in an individual severely affected by MG in order to evaluate the contribution of T cells to the autoimmune response. Clinical improvement was seen when the T-cell response against the AChR was blocked using a treatment called anti-CD4 antibody treatment. The scientists concluded that the transmission of signals between nerve and muscle can be disturbed by a T-cell mediated autoimmune reaction. (Ehlberg, R. et al. Neurology 1994; 44:1732-1737. Both skeletal and cardiac muscle are affected in Duchenne and Becker muscular dystrophies (DMD/BMD), and early diagnosis of heart problems associated with the diseases can improve the management of such problems. Researchers have been examining whether specific dystrophin gene defects are associated with more prominent cardiac complications and recent results reported by researchers in Italy indicate that dystrophin gene deletions involving a certain region (exons 48-49) are more frequently associated with severe cardiomyopathies, although cardiomyopathy can also occur when other types of dystrophin gene defects exist. The research group emphasizes that especially in the early stages of DMD and BMD it is important not to underestimate the cardiac problems that may arise. (Nigro, G. et al. Neuromuscular Disorders 1994; 4:371-379). The series of events that results in muscle fiber damage in DMD is initiated by the lack of dystrophin. Understanding how dystrophin deficiency leads to muscle cell death is important to the effort to develop a therapy for DMD. MDA researchers have participated in studies of mdx mice, which are dystrophin- deficient, that demonstrate mast cells can contribute to muscle damage in DMD. Mast cells in the body are useful in times of injury or infection. However, scientists have found that if mast cells are introduced into mdx mice the destruction of muscle fibers increases whereas this effect is not observed when mast cells are introduced into normal mice that have dystrophin. It is proposed that mast cells may be involved in triggering the process of muscle fiber death when dystrophin is missing. (Gorospe, JRM et al. Neuromuscular Disorders 1994; 4:325-333). The use of muscle cells to transfer the correct version of the dystrophin gene into muscle lacking the gene has been evaluated extensively. MDA researchers have examined the possibility that immune rejection may be causing the low effectiveness in the transfer of muscle cells carrying a therapeutic gene from a donor to a host. A recent study used myoblasts from a donor mouse that were "matched" to the host mouse and would not be expected to trigger immune rejection of the donor cells. After myoblasts were injected into mdx mice and normal mice, the researchers found evidence that the muscle cells introduced into normal mice were present around the injection site and the gene they carried was stable up to one month. However, in mdx mice the gene gradually disappeared and was completely absent by 28 days. This result was apparently due to the ongoing muscle fiber death that occurs in mdx muscle since no evidence of immunorejection of the introduced cells was found. The researchers conclude that myoblast transfer into dystrophin-deficient muscle is most likely not effective because of the rapid loss of the injected myoblasts and the lack of spreading of the myoblasts from the site of injection. (Huard, J. et al. Human Gene Therapy 1994; 5:949- 958). Cells isolated from skeletal muscle tissue can often be studied most effectively in culture dishes in the laboratory. Unfortunately, cells removed from tissue and grown in culture do not survive long and in order to become a useful research tool the cells must be adjusted for survival for extended periods of time. MDA researchers have established such a cell population -- a cell line -- which was derived from a human DMD muscle biopsy. The cell line should be a valuable resource in the study of muscle cell mechanisms and in the study of muscle function problems due to dystrophin deficiency. (Caviedes, R. et al. Muscle & Nerve 1994; 17:1021-1028). Clinical Trial A double-blind, placebo-controlled study assessing the efficacy of Neurontin (gabapentin) in individuals affected by amyotrophic lateral sclerosis (ALS) will be conducted by the Forbes Norris MDA/ALS Center at California Pacific Medical Center in San Francisco. It is possible that Neurontin has antiglutamate properties and could be beneficial in ALS. The one-year trial is open to 150 participants and is expected to begin in October. In the first six months participants will receive either placebo or Neurontin and in the second six month period everyone will be given the drug. More participants are needed for the study and the following centers will be involved: California Pacific Medical Center Robert G. Miller, M.D. and Deborah Gelinas, M.D., Department of Neurology, 3698 California Street, #545, San Francisco, CA 94118; 415-750-6040; 415-750-5022 (fx) University of Colorado Health Sciences Hans Neville, M.D., Department of Neurology, University of Colorado Health Sciences, Denver, CO 80262; 303-270-7221; 303-270-6796 (fx) University of Iowa Hospital Mark Ross, M.D., Department of Neurology, University of Iowa Hospital, Iowa City, IA 52242; 319-356-2065; 319-356-4505 (fx) Loma Linda University Medical Center Carmel Armon, M.D., Department of Neurology, Loma Linda University Medical Center, Loma Linda, CA 92354; 909-824- 4907; 909-824-4692 (fx) University of Minnesota Gareth J. Parry, M.D., University of Minnesota, Department of Neurology, Minneapolis, MN 55455; 612-626-4107; 612-625-7950 (fx) University of Texas - S.W. Medical School Wilson W. Bryan, M.D., Department of Neurology, University of Texas-S.W. Medical School, Dallas, TX 75235-8897; 214-648- 6419; 214-648-2265 (fx) University of Utah Jack Petajan, M.D., Ph.D., Department of Neurology, University of Utah, Salt Lake City, UT 84132; 801-581-8916; 801-581-4192 (fx) In its position statement the clinical research group that will manage the study acknowledges that Neurontin is already available in pharmacies. However, there is a need for a trial to fully evaluate whether the drug, in fact, does provide benefit in light of the expense of Neurontin and the side effects that may be significant in individuals who have weakness as well as compromised breathing or swallowing function. cc: MD Forum [MD-LIST@DATA.BASIX.COM] --- MDA -- Working to find the cure for neuromuscular disease === end of als 132 ===