=============================================================== == == == ----------- ALS Interest Group ----------- == == ALS Digest (#108, 24 June 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 == == 270+ 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 .. ALS clusters 2 .. neurotrophins 3 .. CNTF 4 .. CNTF/BDNF/AXOKINE 5 .. SOD-1 6 .. Neurotrophic Factors? 7 .. amia internet working group (1) ===== ALS clusters ========== Date : Fri, 24 Jun 1994 09:23:31 +0700 >From: bworth@aostra.cuug.ab.ca (Eyon Butterworth) In the ALS Digest the second article concerns ALS clusters (specifically two cases in Des Moines within the same company) I'm looking for information concerning the cluster that involved players from an American Pro football team in the 50 or 60's. I think it was San Fransisco? If you could put me on the right path as to what team it was, the year and the players involved it would be a great help. Thank you. Sincerly, Eyon Butterworth bworth@aostra.cuug.ab.ca (Alberta Department of Energy, Oil Sands and Reseach Division) eyon@cns.ucalgary.ca (University of Calgary, Department of Clinical Sciences) (2) ===== neurotrophins ========== SAN FRANCISCO (JUNE 22) BUSINESS WIRE - June 22, 1994--UC San Francisco researchers have announced findings furthering scientific understanding of how the nervous system develops in response to proteins called neurotrophins, a discovery of potential importance in the treatment of disease. The UCSF scientists suggest that two of these neurotrophin proteins should be investigated for their potential to prevent the death of nerve cells from degenerative diseases or toxic substances. Their conclusion is based on studies of knockout mice, so-named because they are engineered to have a specific gene of interest knocked out so that researchers can look at what happens to mice lacking the protein encoded by the absent gene. The most recent UCSF findings are published in the current issue of Nature (June 23). Isabel Farinas, PhD, a visiting scientist and Fulbright scholar from Spain, and Kevin R. Jones, PhD, a research associate with the Howard Hughes Medical Institute at UCSF, worked with Louis Reichardt, PhD, professor of physiology and biochemistry and biophysics, to perform the studies. There is clinical interest in neurotrophins based on the knowledge that they help nerve cells survive, according to Reichardt, a Howard Hughes Medical Institute investigator at UCSF. If they are provided with the same neurotrophin later in adulthood, many types of nerve cells that require a particular neurotrophin during development are better able to survive exposure to chemicals that normally would kill them, Reichardt said. Biotechnology companies are investing in neurotrophins in the hopes of finding effective treatments for Alzheimer's disease, amyotrophic lateral sclerosis (ALS), and other degenerative disorders. One neurotrophin, brain-derived neurotrophic factor (BDNF) is undergoing trials to investigate its usefulness as a treatment for ALS, a fatal degenerative disease attacking spinal cord nerves that connect to muscles. Another neurotrophin, nerve growth factor (NGF), is being studied for its potential to halt the death of certain forebrain cells in Alzheimer's disease. The UCSF team earlier reported in the March 25 issue of the journal Cell that knockout mice missing BDNF developed abnormally few sensory nerve cells. In addition, nerve cells in certain regions of the central nervous system, such as the hippocampus, a brain region important for learning and memory, developed abnormally in the mice. But the BDNF study refuted earlier work which had suggested that BDNF was required for normal development of motor nerve cells controlling muscle movement, for growth of nerve cells that degenerate during Parkinson's disease, and for development of nerve cells that degenerate during Alzheimer's disease in the basal forebrain. These brain regions appeared to be normal in BDNF knockout mice. Both the NT-3 and the BDNF knockout mice develop many fewer of the sensory nerve cells that relay information used in the regulation of heart rate, blood pressure, respiratory rate, lung airways, gut contractions and functions of other organs. The absence of NT-3 resulted in a reduced number of nerve cells that depend on NGF or BDNF later in development, suggesting that many nerve cells are transiently dependent on NT-3, but later need other neurotrophins. The researchers are interested in studying the consequences of the absence of NT-3 or BDNF on brain function in adult mice. However, the knockout mouse strains developed so far die within days of birth. The team is trying to develop mice that make neurotrophins in some cells but not others, in the hopes that the mice will survive to adulthood, so that physiological and behavioral impacts can be analyzed. CONTACT: University of California, San Francisco Jeffrey Norris, 415/476-2557 (3) ===== CNTF ========== Synergen using lower doses in CNTF trials MINNEAPOLIS, June 23 (Reuter) - Synergen Inc said it is using lower doses of a drug to treat Lou Gehrig's disease than Regeneron Pharmaceuticals Inc used in its trials. Earlier, Regeneron said it would discontinue its late stage trials of the drug, CNTF, due to various adverse side effects. Synergen is also in later trials of the drug. In Synergen's earlier studies of CNTF, Synergen said it did see some adverse side effects that it thought were related the dosage of the drug. However, Ken Collins, Synergen's executive vice president, finance and administration, said the company has been avoiding adverse side affects in subsequent studies by lowering doses of the drug. "We are using lower doses than their (Regeneron's) trial. We haven't announced our doses and they have. Our highest dose is lower than their lowest dose," Collins said. REUTER ==== == Synergen, Inc. == 1885 33rd Street == Boulder, CO 80301-2546 == TEL 303-928-6200 == FAX 303-441-5535 ==== (4) ===== CNTF/BDNF/AXOKINE ========== HEALTH NEWS DAILY (Friday June 24, 1994) Regeneron shifts strategic focus to Axokine second-generation CNTF & BDNF therapies, will incur $450,000 charge in second quarter for strategic refocusing. REGENERON AXOKINE AND BDNF THERAPY ARE FOCUS OF NEW R&D STRATEGY in the wake of the company's June 23 decision to discontinue Phase III clinical trials of ciliary neurotrophic factor for the treatment of amyotrophic lateral sclerosis (ALS, or Lou Gehrig's disease). Regeneron is testing Axokine (second-generation chimeric neurotrophic factor) individually and in combination with brain-derived neurotrophic factor for the treatment of ALS. The compound demonstrated increased potency and greater solubility and stability as compared to CNTF in preclinical studies, and Regeneron expects to file an IND by the end of 1995, the company said. The BDNF molecule is currently in an Amgen-Regeneron Partners clinical trial in the U.S. for the treatment of Lou Gehrig's. ==== == Regeneron Pharmaceuticals, Inc. == 777 Old Saw Mill River Road == Tarrytown, NY 10591-6707 == TEL 914-347-7000 == FAX 914-347-2113/914-347-2815 ==== (5) ===== SOD-1 ========== =============================================== Title : A novel mutation in Cu/Zn superoxide dismutase gene : in Japanese familial amyotrophic lateral sclerosis Author : Nakano R.; Sato S.; Inuzuka T.; Sakimura K.; Mishina M.; : Takahashi H.; Ikuta F.; Honma Y.; Fujii J.; Taniguchi N.; : Tsuji S.; Source : 1994 200/2 (695-703) Biochemical and Biophysical Research : Communications Abstract : Recently, several missense mutations in the Cu/Zn : superoxide dismutase gene (SOD1) have been reported as : a putative cause of chromosome-21q-linked familial : amyotrophic lateral sclerosis (FALS). We have discovered : a novel missense mutation (substitution of Thr for Ala4) : in exon 1 (GCC to ACC) in two FALS patients from one : Japanese FALS family. No mutations were found in 17 : cases of sporadic ALS. The enzyme activity of recombinant : fusion protein containing the Cu/Zn superoxide dismutase : (SOD) with the Ala4-to-Thr mutation was significantly : reduced in E. coli. On the other hand, in the expression : system in insect cells using Baculovirus, the mutant SOD : expressed an enzyme activity as high as wild-type SOD. : These results suggest that the stability of SOD with : the Ala4-to-Thr mutation is disrupted especially in : the fusion protein. Autopsy was carried out on one of : the two patients, and the pathological findings were : typical of FALS with posterior column involvement. : These results raise the possibility that mutation of : the SOD1 is responsible for FALS with broader : pathological involvement. (6) ===== Neurotrophic Factors? ========== Topic 1416 Re: Neurotrophic Factors? bionet.neuroscience 6:59 pm Jun 14, 1994 In article <2nnikt$t1i@news.delphi.com>, rstetta@news.delphi.com (RSTETTA@DELPHI.COM) writes: An additional factor that may play a role is CNTF (ciliary neurotrophic factor). Regeneron has been testing CNTF is ALS patients following some promising results in animals. However, there have been a number of problems concerning sideaffects. See New and Comments in Science a couple or three weeks ago. Motoneurons have been shown contain various species of neurotrophic receptors of the proto-oncogene family trk. For example, TrkB is the high-affinity receptor for BDNF and trkC is the high-affinity receptor for NT-3. p75 the low-affinity neurotrophin receptor, capable of binding all of the known neurotrophins. Its function is not clear and a number of models have been suggested. p75 is expressed in developing motoneurons and motoneurons that have been axomotomized. We are presenting data at next year's Soc. Neurosci. meeting showing a disruption of sensory input also leads to an up-regulation of p75 in motoneurons. David P. Crockett crockett@UMDNJ.EDU (7) ===== amia internet working group ========== Date : Tue, 7 Jun 1994 06:01:02 LCL Sender : Medical Libraries Discussion List : >From : Gary Malet Subject: ANNOUNCE:AMIA INTERNET WORKING GROUP ********************************************************************* CALL FOR PARTICIPATION _____________ "INTERNET WORKING GROUP" _______________ AMERICAN MEDICAL INFOMATICS ASSOCIATION ******************************************************************** Medical professionals, information specialists, and interested individuals are invited to participate in the development of Internet medicine resources. Academic sessions will be held in conjunction with the biannual meetings of the AMIA on the following dates: AMIA-SCAMC Washington, D.C. November 5-9, 1994 AMIA Spring Congress New Orleans, L.A. June 24-28, 1995 Scholarly sessions will focus on Internet search tools, interfaces, data archives, networks, and hardware. Demonstrations by universities, medical schools, and private enterprise will be offerred. The sessions will feature software exchanges and connectivity and installation issues. Awards for innovative Internet programs, products, and databases will be given. The Internet Working Group will provide numerous opportunities to share ideas and expertise about the use of Internet in healthcare. The program will include a wide range of interesting activities including keynote speakers, paper presentations, panel sessions, demonstrations, and hands-on workshops. A preliminary series of talks and panel discussions has been considered: 1. How to connect physicians and hospitals to Internet 2. Mounting text, hypertext, graphics, and multimedia on Internet 3. Demonstration projects by University teams: The Virtual Hospital, NLM's HyperDoc 4. Demonstration by commercial on line vendors: Physician's On Line, etc. 5. Exploring the World Wide Web and Other Internet Tools Mosaic, Cello, WAIS, Lynx, Gopher, etc. 6. Security, standardization, and commercialization of networked medical resources __________________________________________________________________ Please forward the following information to me. Your information will be forwarded to the AMIA membersip committee at amia@camis.stanford.edu to record the interest in these projects. You will also be placed on a mailing list regarding the Internet working group : ------------------------------------------------------------------ Name: Institution: Address: Phone number: Fax number: E-mail address: Computer/Network environment: Current AMIA member? [ ] Yes [ ] No Internet Skill Level: [ ] Beginning [ ] Intermediate []Advanced [ ] Internet Resource Provider Description of your interest and comments: -------------------------------------------------------------------- ***************************************************************************** Dr. Gary Malet |7 W 5th Street | "communication, Family Physician |Stockton, Ca. 95206 | search, Healthtel, Inc.-windows based |VOICE 209-466-6878 | delivery, medical telecommunications |FAX 209-466-0502 | networking" gmalet@surfer.win.net |Compuserve 72630.1535| ***************************************************************************** == end of als 108 ==