Date: Wed, 16 Nov 94 02:26:48 -0500 From: Bob Broedel To: als@huey.met.fsu.edu Subject: ALSD#147 ALS-ON-LINE =============================================================== == == == ----------- ALS Interest Group ----------- == == ALS Digest (#147, 15 November 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 == == 390+ 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 .. Enterovirus and ALS 2 .. Re: Enterovirus and ALS 3 .. Viruses and motor neuron disease: the viral hypothesis lives 4 .. GABA & ALS 5 .. ALS Advocacy Committee Meeting 6 .. biotech report 7 .. Amyotrophic Lateral Sclerosis, info wanted 8 .. amyotrophic lateral sclerosis 9 .. mice, SOD & stroke (1) ===== Enterovirus and ALS ========== Date : Tue, 15 Nov 94 14:19:39 PST >From : scottb@CERF.NET Subject: Enterovirus and ALS In June of 1994, Woodall, Riding, Graham and Clements published an article "Sequences specific for enterovirus detected in spinal cord from patients with motor neurone disease." This study found nucleic acid sequences specific for enterovirus in the spinal cords of 8 of their 11 subjects with motor neuron disease, and in none of the control subjects. Question: Has any further research or theories on this topic been published or discussed since June? Any other strong evidence after June of 1994 (or before!) to support this etiology as one of the causes of MND or sporadic ALS? A related question: Any evidence, research, discussion regarding the possibility that early adult viruses (e.g., epidemic pleuradinia, "Devils Grip", etc.) may in later adulthood cause ALS or MND in the same or mutated form? After much reading during the past two years, I have come to believe that one or more viruses may be responsible for at least many of the MND or ALS cases out there. I would be very grateful for any and all responses, research, documents, discussion, theories, etc. with regard to this matter from the world-wide community that Bob Broedel has assembled on this BB. Respectfully, Scott Internet Address: scottb@cerfnet.com (2) ===== Re: Enterovirus and ALS ========== Date : Tue, 15 Nov 94 16:10:24 EST >From : Mike Doliton" To : scottb@CERF.NET, bro@huey.met.fsu.edu Subject: Re: Enterovirus and ALS Scott: I read that discussion about the 8 out of 11 autopsies leading to some belief that a virus could cause MND. I can attest that after having a bad cold that I started to get a slurring in my voice. I always felt that a virus or bacteria could live in a person's body after the cold was gone and surface in one of the organs and cause great damage. Of course I have no proof that in my case the MND could be just coincidental to the cold. I called a research doctor down in Texas at Baylor and his nurse said that they believed that MND or ALS could be caused by a virus. I haven't read anything on Bob's bb or on Prodigy about this virus theory lately. It needs looking into. I don't know how to get things going in this area of research. Maybe other people here do know how to get research going. Regards, Michael Doliton, Sony Medical Systems (3) ===== Viruses and motor neuron disease: the viral hypothesis lives ========== Michael, I don't know how to get research going, but we will do our best to locate people who are already doing it. There is a book entitled, MOTOR NEURON DISEASE. It is edited by A.C. Williams (Chapman & Hall Medical; 1994; 755 pages, hard cover). Chapter 27 of this book is VIRUSES AND MOTOR NEURON DISEASE: THE VIRAL HYPOTHESIS LIVES. The chapter is written by Dorothy C. Kelley- Geraghty and Burk Jubelt (both are at: Department of Neurology; College of Medicine; State University of New York; 750 East Adams Street; Stracuse NY 13210 USA). Here is a quote from their chapter. "We will try to show how the epidemiological evidence, virus infections in MND, latent virus infection in other diseases and finally the immunological findings all support a viral hypothesis." At the end of the chapter is a listing of over 100 references to the topic. I suggest that all interested folk go to the library and try to locate this important book. Also, I will do a quick MEDLINE search using the keywords AMYOTROPHIC and (VIRUS or VIRAL). Will clean up the results and will post the results of that search (a dozen or so references) in ALS Digest 148. rgds,bro (4) ===== GABA & ALS ========== PART (1) ========== Date : Mon, 14 Nov 1994 20:36:25 -0500 >From : Victor Blok Subject: GABA, possible protective effect I wonder whether anybody ever considered trying GABA agonist drugs in ALS. Has anyone heard of any controlled human studies or mice experiments in this regard? I believe these drugs should be effective in protecting nervous cells - although this is rather intuitive statement. Also, motor neurons may be somewhat different in their properties. GABA agonists are widely used in medicine and have minimal side effects. However, my attempts to find anything relevant through MedLine database (Johns Hopkins University's Welch Medical Library) failed. Sincerely, Victor Blok PART (2) ========== Date : Tue, 15 Nov 1994 17:44:32 -0500 >From : Victor Blok Subject: Re: GABA & ALS Dear Mr. Broedel, It is OK to put my question in ALS digest, what I try to say is that though GABA metabolism seems to be normal in ALS patients, very well may be that increased production may somewhat compensate abnormal methabolism of glutamate and somewhat protect motor neurons. And yes I am Russian, though I am US citizen and I am 7 years in the US. Sincerely, Victor Blok PART (3) ========== MEDLINE - SET SEARCH TERMS GABA and AMYOTROPHIC =================================================== 1. Muscle cramp as the result of impaired GABA function--an electrophysiological and pharmacological observation. 2. Decreased glutamate transport by the brain and spinal cord in amyotrophic lateral sclerosis [see comments] 3. Brain amino acid contents are dissimilar in sporadic and Guamanian amyotrophic lateral sclerosis. 4. Amyotrophic lateral sclerosis: glutamate dehydrogenase and transmitter amino acids in the spinal cord. 5. Characterization of dissociated monolayer cultures of human spinal cord. 6. Synaptosomal glutamate uptake declines progressively in the spinal cord of a mutant mouse with motor neuron disease. =================================================== Document No : 94019522 Title : Muscle cramp as the result of impaired GABA function--an : electrophysiological and pharmacological observation. Author : Obi T; Mizoguchi K; Matsuoka H; Takatsu M; Nishimura Y Source : Muscle and Nerve 1993 Nov;16(11):1228-31 =================================================== Document No : 92244308 Title : Decreased glutamate transport by the brain and spinal : cord in amyotrophic lateral sclerosis [see comments] Author : Rothstein JD;Martin LJ;Kuncl RW Source : New England Journal of Medicine : 1992 May 28;326(22):1464-8 =================================================== Document No : 91066184 Title : Brain amino acid contents are dissimilar in sporadic and : Guamanian amyotrophic lateral sclerosis. Author : Perry TL; Bergeron C; Steele JC; McLachlan DR; Hansen S Source : Journal of the Neurological Sciences : 1990 Oct;99(1):3-8 =================================================== Document No : 92193920 Title : Amyotrophic lateral sclerosis: glutamate dehydrogenase : and transmitter amino acids in the spinal cord. Author : Malessa S; Leigh PN; Bertel O; Sluga E; Hornykiewicz O Source : Journal of Neurology, Neurosurgery and Psychiatry : 1991 Nov;54(11):984-8 =================================================== Document No : 89229982 Title : Characterization of dissociated monolayer cultures of : human spinal cord. Author : Erkman L; Touzeau G; Bertrand D; Bader CR; Kato AC Source : Brain Research Bulletin 1989 Jan;22(1):57-65 =================================================== Document No : 93203895 Title : Synaptosomal glutamate uptake declines progressively in : the spinal cord of a mutant mouse with motor neuron disease. Author : Battaglioli G; Martin DL; Plummer J; Messer A Source : Journal of Neurochemistry 1993 Apr;60(4):1567-9 ==================================================== (5) ===== ALS Advocacy Committee Meeting ========== Date : Tue, 15 Nov 1994 15:26:47 -0600 (CST) >From : HEINET@wartburg.edu Subject: ALS Advocacy Committee Meeting The ALS Association's Advocacy Committee met in Philadelphia on November 5, prepatory to an ALS Association Board meeting the following week. Purpose of the Advocacy Committee's meeting was for the committee to seek patient input that could be forwarded to the national assciation's board. Genesis of the meeting was a feeling that activist patients on the Prodigy ALS bulletin board had been overly critical of the Advocacy Committee and its work and that a get-together would help clear the air and focus clearly on short and long-term goals. Chair of the Advocacy Committee is Ellyn Phillips who is also president of the Philadelphia chapter of ALSA. Other committee members in attendance were Dara Alexander of Ohio and Florida, Joshua Javits of Wasahington DC, Ben Ohrenstein of Philadelphia. Technical consultants were Dr. Hiroshi Mitsumoto of Cleveland and Lynn Klein, VP of Patient Services of ALSA. Patients participating were Jack Norton of Minnesota, James Rather of New York, Stephen Pie' of Delaware, Ted Heine of Iowa, and caregiver Linda McKnight of Seattle. Details of the meeting have been posted on the Prodigy ALS bulletin board. Hosever, highlights were a presentation by Jack Norton outlining patient goals: 1. Human combination trials of CNTF and BDNF as soon as possaible. 2. Compassionate (extended) access by patients to promising drugs as soon as Phase III of clinical trials assures safety and some promise of efficacy. 3. Ending use of placebo controls in ALS clinical trials. Discussion highlighted following: 1. Combination trials of CNTF and BDNF must await animal safety trials of the combined drugs. Timeline for completion of such should be late winter of 1995; following which a small human trial could be proposed to the FDA. 2. Compassionate (extended) access is authorized by FDA regulations in Phase III of clinical trials. but it is up to the drug companies to propose such. Companies may charge enough for the drug to recover costs but not make a profit. Drug companies need to be encouraged to do this. 3. Recent and ongoing clinical trials of ALS drugs have created a population of approximately 1,000 patients who have received placebo but have been followed on a monthly basis to determine progression. These could serve as historical placebo controls for future clinical trials using similar patient evaluation protocols, provided: 1. placebo patient data is available in a convenient repository, and 2. one more clinical trial with placebo controls is then undertaken and its results compared to the historical data bank. However, if one (or more) the the drugs presently in clinical trials demonstrates efficacy, that care would become the standard of care for ALS and other drugs would be compared to it, obviating the need for placebo controls. Meeting was very helpful in assuring patients that ALSA is committed to all possible speed in seeking drug treatments for ALS, and that the Advocacy Committee will communicate developments to the ALS patient community as rapidly as feasible. Ted Heine, Waverly, Iowa (6) ===== biotech report ========== BIOTECHNOLOGY (INDUSTRY REPORT) PAINEWEBBER INC.: Miller, L.I. 28 Pages September 26, 1994 < most of this 28 page copyrighted document has been deleted > Key events for the quarter: Cephalon's Myotrophin Synergen's CNTF Upcoming meetings and events: information overload * Completion of Phase III clinical trials for Amgen's Infergen and Neupogen (community acquired pneumonia); Cephalon's Modafinil and Myotrophin; Cor's Integrelin; and, Synergen's CNTF. Medical and Scientific Meetings Society for Neuroscience 11/13-17 Miami Cephalon Near-Term Milestones By Company 1994-95 Amgen BDNF ALS Completion of Phase I/II dose escalation study 1994-Q1 1995 Cephalon Myotrophin ALS Completion of North American Phase II/III clinical trial Q4 1994; preliminary analysis Q1 1995; Completion of European Phase II/III clinical trial mid-1995, data analysis 2H 1995 Synergen CNTF ALS Completion of Phase II/III clinical trial Q4 1994, presentation of data H1 1995 (7) ===== Amyotrophic Lateral Sclerosis, info wanted ========== PART (1) ========== Newsgroup: de.sci.medizin >From : rikard@dc.luth.se (Rikard Stenberg) Subject : Amyotrophic Lateral Sclerosis, info wanted Dear Sir/Madam! I am looking for information regarding "Amyotrophic Lateral Sclerosis". Please reply to this BY E-MAIL if you have recent publications or information about ALS. THANKS for your friendly cooperation. Tuula Bergqvist, Sweden (tuula@centek.se) PART (2) ========== Newsgroup: sci.med.50931 >From : norbert@gia.rwth-aachen.de (Norbert Berzen) Subject : Re: Amyotrophic Lateral Sclerosis, info wanted rikard@dc.luth.se (Rikard Stenberg) writes: > >Dear Sir/Madam! >I am looking for information regarding "Amyotrophic Lateral >Sclerosis". Please reply to this BY E-MAIL if you have recent >publications or information about ALS. >THANKS for your friendly cooperation. >Tuula Bergqvist, Sweden (tuula@centek.se) > There's a newsletter of the ALS Interest group. To subscribe it you must send E-Mail to bro@huey.met.fsu.edu with the following body subscribe ALS DIGEST The actual issue #146. Best regards Norbert [norbert@dune.gia.rwth-aachen.de] (8) ===== amyotrophic lateral sclerosis ========== Newsgroup: sci.med.telemedicine >From : Bob Broedel Subject : amyotrophic lateral sclerosis As always, we of the ALS Interest Group are seeking information about motor neuron experts who are on-line. We now have 390+ subscribers but we are always looking for more interested folk. If your specialty is ALS, please send me a message. Thanks! ======================= ========================== Bob Broedel, Engineer = Strike Out ALS ! = Meteorology Department = (Lou Gehrig's Disease) = FLORIDA STATE UNIVERSITY = List Owner: = Tallahassee, Florida 32306-3034 USA = ALS INTEREST GROUP = ================================================================ TEL: 904-644-6840 (work, answering machine), 904-576-4906 (home) FAX: 904-644-9642 ATTN:BROEDEL E-mail: bro@huey.met.fsu.edu TELEX (AT&T EasyLink): 5106014520 (TALLY-KRAS FL) ================================================================ 24 hour active radio-telephone (hand-held cellular) 904-556-4286 ================================================================ (9) ===== mice, SOD & stroke ========== By LIDIA WASOWICZ UPI Science Writer SAN FRANCISCO, Nov. 14 (UPI) -- An enzyme shown in animals to deactivate destructive molecules that otherwise would wreak havoc in nerve cells after brain injury coutment for trauma or stroke patients, researchers said Monday. < parts deleted because of copyright > While no treatments are available to limit the extent of brain-cell death in the hours following such injury, a number of possible therapies are undergoing animal and human tests. One promising candidate is an enzyme called copper-zinc superoxide dismutase, SOD, which converts destructive "free radicals" into harmless molecules, said Pak Chan, head of the Central Nervous System Injury and Edema Research Center at the University of California, San Francisco, who presented the findings at the annual meeting of the Society for Neuroscience in Miami. He and his team inserted extra copies of the SOD gene into mice and studied their offsprings, some of which inherited the extra copies and some of which did not. "Our most recent studies show mice which inherited the ability to make higher than normal amounts of the protective enzyme in their brains recover from brain trauma to a significantly greater degree than their genetically normal litter-mates," Chan said. The mice that made more enzyme regained weight more rapidly following brain injury and retained more control over their movements, said co- researcher Dr. Charles Epstein, professor of pediatrics at UCSF. "Mice that overproduced superoxide dismutase were better able to balance themselves and walk on a beam following brain trauma, in comparison to their normal litter-mates who made only normal amounts of superoxie dismutase," he said. < parts deleted > Injured cells are more prone to undergo oxidation, chain reactions with oxygen that lead to the production of free radicals, which can kill cells by attacking the fatty lipids in their membranes, DNA and protein. SOD inactivates superoxide -- the first molecule produced in this errant process -- before it sets off free-radical damage. Chan and his team are working on developing microscopic fat sacs, called liposomes, that might provide a suitable vehicle for delivering SOD to the brain to prevent death of cells that survive the cut-off of blood supply during stroke. "The reduction in free radicals brought about by SOD also seems to improve the brain cells' ability to respond to stroke and trauma by making 'heat-shock' proteins that, like SOD, seem to help prevent injured brain cells from dying," said Dr. Shigeki Mokawa of Chan's lab. === end of als 147 ===