=============================================================== == == == ----------- ALS Interest Group ----------- == == ALS Digest (#119, 18 August 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. Currently there are == == 300+ 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 .. Mega-Vitamin-Enzyme 2 .. FDA Ethics Questioned 3 .. MDA Research Report #49 (1) ===== Mega-Vitamin-Enzyme ========== Date : Wed, 17 Aug 1994 11:51:00 -0700 (PDT) >From : Mark Chu 360-7388 Subject: Mega-Vitamin-Enzyme I have been receiving your emails on behalf of an ALS patient. He was hoping to post the following note ... Thanks Mark Chu ----------------------------- Notice: Have any ALS patients or caregivers had success with MEGA-VITAMIN-ENZYME treatment. Has anyone had dealings with Frank Ludde of North Vancouver B.C., who claims he can cure ALS with this treatment. Danny Meyer (2) ===== FDA Ethics questioned ========== FDA ethics questioned By LISA M. SEACHRIST UPI Science Writer WASHINGTON, Aug. 10 (UPI) The clinical trials needed for U.S. Food and Drug Administration drug approval are unethical and in direct violation of world-wide standards, the editor of the journal Epidemiology said Wednesday. The FDA's testing requirements unnecessarily and unethically place study participants at risk, said Kenneth Rothman of Boston University School of Public Health. Writing in this week's New England Journal of Medicine, Rothman and coauthor Karin B. Michels assert the FDA's requirements violate the 1964 Declaration of Helsinki that requires every patient in a clinical study be assured of the best diagnostic and therapeutic care. The Helsinki Declaration was based on the Nuremberg Code which was formulated in response to Nazi atrocities during World War II. The code is considered to be the cornerstone of modern human experimentation ethics. FDA requires that a new drug must be proven to be safe and effective in order to get approval. The ``gold standard'' test to determine a drug's effectiveness is the placebo-controlled study where one group of patients receives the drug and the other gets a completely inactive sugar pill known as a placebo. ``Patients receiving a placebo during a clinical trial where there is a treatment known to be effective are not receiving the best therapeutic method available,'' says Rothman. ``The code is very clear that is unethical.'' ``In trials where there is no standard treatment, a placebo-controlled is fine,'' said Rothman. ``But, there are an awful lot of placebo- controlled studies that require explanation for the use of placebo.`` (3) ===== MDA Research Report #49 ========== Date : 17 Aug 94 15:33:55 EDT >From : Barry Goldberg <71154.330@compuserve.com> Subject: MDA Research Report #49 -- Part 1 This message was originally addressed to MD Forum [MD-LIST@DATA.BASIX.COM] and a carbon copy was sent to you. ---------------------------------------- Sorry this is late but I'm trying to catch up on passing along these MDA Research Reports. Here's part one of #49: June 30, 1994 TO: MDA Clinic Directors FROM: Norine Stirpe, Ph.D. Director of Research Development RE: Research Update #49 An animal model of one form of familial amyotrophic lateral sclerosis (ALS) has been developed. Using transgenic technology, MDA-supported researchers introduced defective superoxide dismutase (SOD1) genes into mice that then developed a motor neuron disease. The researchers' results confirm that certain defects in SOD1 are involved in familial ALS. The model will allow testing of potential therapeutics. (Gurney, M.E. et al. Science 1994; 264:1772-1775). During their search to understand the causes of neuromuscular diseases MDA researchers occasionally discover new relationships between cell components. Three research groups independently determined that a component involved in maintaining the integrity of the muscle cell membrane and a component involved in the signaling process between nerve and muscle can actually interact with one another. Alpha-dystroglycan is a member of the complex of proteins that link with dystrophin to provide stability for the muscle cell membrane. Agrin is a protein that is responsible for gathering acetylcholine receptors together at the neuromuscular junction to participate in the passage of signals from nerve to muscle. From these descriptions, it would appear that alpha-dystroglycan and agrin are unrelated, however, the scientists have shown that they can interact with one another. This discovery will lead to a better understanding of how neuromuscular diseases that affect either the dystrophin complex or components at the neuromuscular junction can develop (i.e., Duchenne or Becker muscular dystrophy and myasthenia gravis). (Bowe, M.A., et al., Neuron 1994; 12:1173-1180; Campanelli, J. et al. Cell 1994; 77:663-674; and Gee, S. H. et al. Cell 1994; 77:675-686). Friedreich ataxia (FA) is linked to a region on chromosome 9 and MDA researchers are involved in studies to find the defective gene that results in the disorder. Recently scientists have narrowed the area that they need to analyze in order to find the gene. Their advance is encouraging since they have a much smaller part of the chromosome in which to look for the gene that has defects in individuals affected by FA. (Rodius, F. et al. American Journal of Human Genetics 1994; 54:1050-1059). Myotonic dystrophy (DM) results from an unusual genetic defect called unstable DNA. The defect involves a certain sequence of DNA that is repeated too many times. The more the repeats the more severe is the disease. The congenital form of DM has a high number of repeats and, curiously, appears to be inherited from mothers, not fathers, who are affected by the disease. MDA- supported scientists are beginning to sort out why congenital DM appears to be inherited only from mothers who have DM. From the observations thus far, it is proposed that the offspring of a mother with DM may experience effects from inheriting the disease gene as well as metabolic effects of the mother's disease on the fetus. Further studies are necessary to attain the answer. (Barcelc, J.M. et al. American Journal of Human Genetics 1994; 54:1124-1125). A successful gene therapy for Duchenne muscular dystrophy (DMD) would require the appropriate delivery of the dystrophin gene to where it is needed in the body, and long-term expression of the dystrophin gene. MDA researchers believe that the adenovirus could be used effectively as a carrier of the dystrophin gene since it fulfills many of the criteria necessary for a muscle gene therapy. Different aspects of the functions required of an adenoviral vector are being tested. MDA scientists recently reported that immature muscle cells in mice were able to take up an efficient quantity of the viral vector because these cells have a large number of locations for the virus to enter the cell. This information is useful for the design of a DMD gene therapy. (Acsadi, G. et al. Human Molecular Genetics 1994; 3:579-584). Spinal muscular atrophy (SMA) researchers who are part of the MDA-supported SMA working group are making progress toward identifying the disease gene. Certain markers that allow scientists to examine characteristics of the area of the chromosome that contains the SMA gene have revealed specific features of the chromosomal area that should speed the ability of the researchers to locate the gene affected in SMA. (Melki, J. et al. Science 1994; 264:1474-1477). Date : 17 Aug 94 15:33:37 EDT >From : Barry Goldberg <71154.330@compuserve.com> Subject: MDA Research Report #49 -- Part 2 ---------------------------------------- Here is part two of Research Report #49 -- Certain mice called dy mice are affected by a form of muscular dystrophy that mimics human forms of the disease such as Duchenne muscular dystrophy (DMD), although dystrophin is not defective in the dy mouse. In order to determine the genetic basis of this dystrophy in mice, investigators have examined various muscle cell components such as the dystrophin-associated proteins. Although some of these proteins are deficient in human forms of dystrophy, these proteins were not found to be affected in the dy mouse. Therefore, MDA researchers began examining the muscle cell components that interact with the complex of dystrophin and its associated proteins, and have now established that the merosin gene is affected in the dy mouse. Merosin is a protein located in the external environment of the muscle cell and it is part of the structure to which the muscle cell attaches in order to maintain stability within muscle tissue. (Xu, H. et al. Proceedings of the National Academy of Science USA 1994; 91:5572- 5576 and Sunada, Y. et al., Journal of Biological Chemistry, in press.) Dystrophin is a member of a class of proteins involved in maintaining cell structure. Dystrophin, along with other proteins like beta-spectrin, is found in muscle cells. MDA- supported researchers looked to see whether the deficiency of dystrophin in Duchenne muscular dystrophy (DMD) affected the related structural protein beta-spectrin. The scientists found that beta-spectrin exists in normal amounts in individuals with Becker muscular dystrophy (BMD) whose dystrophin levels are not severely affected; however, the expression of the protein is abnormal in DMD. This is yet another demonstration of the fact that the lack of dystrophin can alter other muscle proteins. (Minetti, C. et al. Neurology 1994; 44:1149-1153). Individuals with phosphofructokinase (PFK) deficiency experience muscle fatigue which after exercise can lead to severe muscle cramps and other problems. These symptoms are usually noticed in the teenage years or early adulthood. The natural history, or characteristics of the progression of PFK, is not well understood. Defects in the PFK gene on chromosome 1 have been described, and such defects found in the Ashkenazi Jewish population appear to be associated with late-onset weakness that can result in a more severe myopathy. Evaluating the expression of the disease while knowing the particular gene defect involved will help researchers predict the course of PFK. (Argov, Z. et al. Neurology 1994; 44:1097-1100). Intravenous immunoglobulin (IVIG) is being used in several disorders including myasthenia gravis and the inflammatory myopathies; however, complications can arise. One case recently reported a young woman with myasthenia gravis who developed blood clots on the brain and other problems following a course of IVIG. The clinicians state that IVIG cannot be established as the cause of the problems, however, they urge physicians to be aware of the complications associated with IVIG that could possibly arise in individuals of any age. (Steg, R.E. and Lefkowitz, D.M. Neurology 1994; 44:1180-1181). Clinical Trials Regeneron Pharmaceuticals, Inc. announced on June 23 that they have halted their Phase III clinical trials of ciliary neurotrophic factor (CNTF). Based on a recent review of the data compiled thus far, the company has determined that "any modification or extension of the study would not be sufficiently productive." Regeneron will be focusing its neurotrophic factor research in other areas that include; brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and Axokine, which is related to CNTF. However, Synergen, Inc. is continuing its CNTF trials which should conclude at the end of 1994. The company expects to have the results of the multi-center study analyzed sometime early next year. There have been no safety concerns due to side effects in the Synergen study. A quantitative natural history study of facioscapulohumeral muscular dystrophy (FSHD) is being conducted by Dr. Robert Griggs' group at the University of Rochester. Sixty families have been screened to date and the group is seeking additional interested participants. An annual three-day visit is required which involves a series of blood tests and muscle testing. The purpose of the study is to obtain information for the future evaluation of potential therapeutics. Interested participants may contact Lynn Cros, RN at (716) 275-2559. cc: Bob Broedel -- ALS Interest Group [bro@huey.met.fsu.edu] --- MDA -- Working to find the cure for neuromuscular disease == end of als 119 ==