=============================================================== == == == ----------- ALS Interest Group ----------- == == ALS Digest (#100, 12 May 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 == == 240+ 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 .. back issues of ALS Digest 2 .. ALS Discussion Group 3 .. Gene finding 4 .. ALS and SOD1 5 .. new periodical, CNS DRUG 6 .. ALS organizations in Canada 7 .. ALS - recent articles (1) ===== back issues of ALS Digest ========== > >From : ianp@carina.unm.edu (ian FRI NDS.IN.TIME phillips) >Subject: Re: ALSD#87 ALS-ON-LINE >Date : Mon, 9 May 1994 18:47:10 -0600 (MDT) > >Hi, >I am trying to get ALS #82 & #83. >I have sent this message: INDEX ALS > GET ALS ALSD82 > GET ALS ALSD83 >to LISTSERV@mailer.fsu.edu >and get "sorry no files...." > >Can you send me the issues or tell me what I am doing wrong? > >Thank you >Ian > Ian ... You did everything correctly. But some weeks ago there was a change in management at "mailer.fsu.edu". By mistake, the entire directory was destroyed, hence back issues of the ALS Digest are no longer there. When I get a few extra minutes I will restore those files and will announce this to readers of ALS Digest. I think it would be a good idea to store those back issues in a few other places that can be accessed via FTP, Veronica, Gopher, Mosaic, etc ... and especially via e-mail (for those not connected directly to the Internet). Any volunteers? If so, please get in touch with me. Bob Broedel ... bro@huey.met.fsu.edu (2) ===== ALS Discussion Group ========== > >Date: Tue, 10 May 1994 08:07:54 -0600 (MDT) >From: Diane Barbour WSC Denver >Subject: ALS Discussion Group > >Bob - > >I heard through CompuServe that you offer an ALS discussion group. >My mother was diagnosed with ALS last June. Last week my father >and I attended a support group sponsored by MDA, which is the only >group available in Denver that deals with ALS. It really didn't >answer our questions; this group was dedicated more toward the MD >patients. I am interested in trying to get something started that >deals solely with ALS. Can I do that myself, or are there certain >channels that I need to go through? Should I be able to ask the >MDA for a facilitator, or speaker? I think an ALS support group >is necessary in Denver; I've already met several people who would >be interested in attending. Thanks in advance for your help!! > >Diane > Diane, I suggest that you contact the following: The ALS Association Denver Colorado Support Group Kelly Charles 7743 S. Steele Street Littleton CO 80122 TEL 303-843-0770 (home) If that doesn't work please call Ms. Doby Hall at the ALS Association TEL 818-340-7500, FAX 818-340-2060 to find out who the contact person is for Denver. rgds,bro (Bob Broedel) (3) ===== Gene finding ========== >From : Tony McDonough Date : Tue, 3 May 94 13:00:58 BST Subject: Gene finding I saw a mail with regard to the conference some of the group attended.. This mentioned the finding of a neurofilament gene in the sporadic case of ALS. Does anyone have any more info on this? Do they know the exact mutation? Also if so is gene therapy an option? Regards Tony (4) ===== ALS and SOD1 ========== == PART 1 == Date : 10 May 1994 10:59:13 -0500 (EST) >From : ROSEN@HELIX.MGH.HARVARD.EDU Subject: Re: // Dan Rosen // request re ALS list // Bob, I have no objections to you including my notes to Tony in the ALS Digest. However, please include 1 correction. The number of SOD1 mutations is actually about 25, not 35 (this was a typo). We have some papers in press. Do you think the netters would be interested in the abstracts of these? Thanks for all, Dan Rosen == PART 2 == >From : Tony McDonough Date : Tue, 3 May 94 13:00:58 BST I have attached some exchanges of mail I have had with Dan Rosen. He was kind enough to respond to my questions. Date : 20 Feb 1994 14:51:34 -0500 (EST) >From : ROSEN@HELIX.MGH.HARVARD.EDU Subject: ALS and SOD1 Tony, Saw your message in the ALS Newsletter and thought I'd respond to a couple of your questions. With regard to SOD1 mutations and familial ALS, only about a quarter of familial ALS cases have SOD mutations. We have identified about 35 different single DNA base pair substitutions in the SOD1 gene, all in ALS patients with familial ALS. No SOD1 mutations have been found in sporadic ALS patients. We and others have found that these mutations reduce the enzymatic activity of the Cu, Zn superoxide dismutase (the product of the SOD1 gene) to about 50% of normal levels. We have observed these reductions in individuals in the ALS families we have collected who appear to be in good health. Given the number of diferent mutations, all associated with ALS, and none ever found in normal individuals, I think it is very safe to say these mutations cause ALS. Whether it is by a direct or indirect route we cannot currently say. As you speculate, there may in fact be some environmental trigger that precipitates onset of the disease. We (at least I) believe it is the presence of the bad copy of the SOD1 gene (more likely its protein product) that is causing ALS. In other words, I don't think that a simple reduction in SOD activity is the cause of the disease. We are trying to demonstrate this now with animal models. With regard to neurotrophic factors: they are being offered as a panacea for a variety of neurological diseases, including ALS. I think that it is probably wise to maintain a sceptical attitude towards them, at least until it is demonstrated that they have more than marginal effects in slowing or stopping any disease. But, at least for now, they offer some hope, and like chicken soup, they (probably) couldn't hurt. Dan Rosen == PART 3 == Date : 21 Feb 1994 11:38:53 -0500 (EST) >From : ROSEN@HELIX.MGH.HARVARD.EDU Subject: Re: Thanks (some more) Tony, >From my experience with ALS, a positive attitude is a powerful weapon. I think it's really good that you are keeping your spirits up. The decrease in SOD activity probably contributes somewhat to the disease state, since it places a burden on the cell. But it probably is not the primary cause, since the good copy of the gene should be able to compensate somewhat for the loss of activity (SOD has the highest catalytic rate of all known enzymes). Also, in genetic systems in general, loss of function from one copy of a gene rarely causes bad effects (that's probably why we have two copies of most genes). The evidence that it is the presence of the bad copy that is causing the disease stems from the observation that all known mutations of SOD do not interfere with expression of the bad gene. That is, no mutations have been found where the ALS-SOD gene is so badly damaged that its product cannot be made, either entirely or in part. Currently, this is a hypothesis, but a good one, and ultimately, I believe it will be shown to be true. To prove this theory, we and others are trying to put a bad copy of the SOD gene into mice and see if they get ALS. If they do, I think that will be enough to prove a) the mutations in SOD cause ALS and b) the presence of the bad SOD is required to cause the disease. Currently, we do not know how the SOD mutations eventually kill motor neurons (Or why, for that matter, they seem to kill ONLY motor neurons). There are other diseases where similar things are happening (eg, retinitis pigmentosa) and we are trying to figure this out. Some really good ideas have been proposed and we are trying to look at all of them, but it's really hard because we are unsure of what we are looking for. I think eventually (2-3 years max) someone will figure this out. One possibility for gene therapy (possibly the current best option) would be to put in extra doses of the SOD gene to try to "swamp out" the bad effects of the mutant SOD gene. This might work, and the technology is available. But we do not know if extra doses of the SOD gene can cause harm -- the cure might be as bad as the disease. There are currently trials for combination antioxidants and for SOD infusion into the spinal fluid. I'm not sure if either of these will work, but they are not likely to do any harm either. (Since this discovery, I have begun taking vitamins C and E). I forgot to mention in my initial response that because we still have familial ALS cases without SOD mutations, that there are probably other genes out there that cause ALS, and we are looking for them. So, yes, ALS is in fact a collection of very similar disesaes with apparently different causes. I find your questions to be quite penetrating and perceptive -- not "dumb" at all. In fact, I would like to thank you for helping me to clarify my thoughts on what's going on with SOD in ALS. Wishing you good health, Dan Rosen (5) ===== new periodical, CNS DRUG ========== Date : Thu, 12 May 1994 10:23:25 -0700 Sender : Medical Libraries Discussion List >From : Dennis Ritchey Subject: Re: ? Pharmastat I am the librarian for the Drug Information Service of Kaiser Permanente in Southern California. While the name Pharmastat rings some kind of bell, I can't tell you why. I have checked all my sources and find nothing. I am wondering if perhaps your pharmacist was thinking of file 128 on DIALOG, Pharmaprojects. This database reports on the progress of new pharmaceutical products, from early studies to launch. I'll warn you however, unless you subscribe to the print version of the same name, this is a very expensive database. Each record printed is $75.00, and there is not free format for browsing. (if you subscribe to the printed version, the price drops to $3.30 per record...quite a difference.) Your patron might also be interested in a new journal from adis international called CNS DRUG : The clinical review journal of drugs and therapeutics in psychiatry and neurology. It began publication in Januray. One of the tag lines on the flyer is "fully reviews and evaluates all aspects of new and emerging psychiatric and neurological drugs..." It runs about $540.00 per year, but publications from this publisher are excellent, we subscribe to several of their titles. They will send you a sample copy by calling (215) 741-5200. Well, I hope this is of some help. As I said, Pharmastat rings a bell, but I sure can't find anything on it. Good Luck, and if you find out anything about Pharmastat and exactly what it is, please let me know. Dennis Ritchey Medical Librarian Kaiser Permamente Drug Information Service Downey, CA V - (310) 803-2938 F - (310) 803-2550 kpscdrug@cerf.net On Wed, 11 May 1994, Margaret Vugrin wrote: > I hope someone out there can help. > > I've got a new Pharmacologist on faculty who asked me to do a > search on Pharmastat - she explained that it was on DIALOG. > I said sure however, it's not listed in the blue pages so I'm > wondering if this is something else, not a database on DIALOG> > > It has information on drugs on trial, phases, company etc. She > is particulary interested in drugs and CNS. > > Thanks for your help. > > Margaret Vugrin > Information Services Librarian > TTUHSC Library > hlrmv@ttacs.ttu.edu > (6) ===== ALS organizations in Canada ========== Sharon Weir ALS Society of Alberta Rm. 108, 5920 - 1A St. S.W. Calgary, Alberta T2H OG3 CANADA TEL 403-255-1020 FAX 403-255-1036 Allan Graham ALS Society of British Columbia 411 Dunsmuir St. 2/F Vancouver, B.C. V6B 1X4 CANADA TEL 604-685-0737 FAX 604-685-0725 Murray Jordan ALS Society of Manitoba 86 Dickens Drive Winnipeg, MB R3K OM2 CANADA TEL 204-949-0387 FAX 204-694-6204 Darrel McLean ALS Society of New Brunswick 204 Willow Avenue Fredericton, New Brunswick E3A 2E4 CANADA TEL 506-472-7741 FAX ?? Cheryl Power ALS Society of Newfoundland P.O. Box 844 Cornerbrook, Newfoundland A2H 6H6 CANADA TEL 709-634-2435 FAX ?? Brian Smith ALS Society of Nova Scotia P.O. Box 852 Dartmouth, Nova Scotia B2Y 3Z5 CANADA TEL 902-646-1027 FAX 902-465-2581 Ray Lapointe ALS Society of Ontario 2025 Sheppard Ave. E., Suite 4415 Willowdale, Ontario M2J 1V7 CANADA TEL 416-497-2267 FAX 416-497-1256 Marie Salamoun-Dunne ALS Society of P.E.I. 202 Cousins Court Summerside, P.E.I. C1N 5S7 CANADA TEL 902-436-0094 FAX ?? Louise Gagne ALS Society of Quebec 3958 Dandurand St Montreal, Quebec H1X 1P7 CANADA TEL 514-276-7722 FAX ?? Eileen Walkeden ALS Society of Saskatchewan P.O. Box 123 Tribune, Saskatchewan S0C 2M0 CANADA TEL 306-456-2221 FAX ?? This information provided by: Amyotrophic Lateral Sclerosis Society of Canada 90 Adelaide Street, East, Suite B101 Toronto, Ontario M5C 2R4 CANADA TEL 416-362-0269 FAX 416-362-0414 date of list: February 11, 1994 (7) ===== ALS - recent articles ========== ================================================ Title : Pathogenic mechanisms in sporadic amyotrophic lateral : sclerosis. Author : Eisen A; Krieger C Source : Canadian Journal of Neurological Sciences : 1993 Nov;20(4):286-96 Abstract : In recognition of the 100th anniversary of Charcot's death we have reviewed possible pathogenic mechanisms in amyotrophic lateral sclerosis (ALS). Advances in the last 5 years in molecular biology and genetics have identified mutations in the cytosolic dismutase (SOD1) gene in some patients with familial ALS raising the possibility that oxidative stress may be involved in the pathogenesis. An excitotoxic pathogenesis has been implicated based on elevated plasma and CSF levels of amino acids and altered contents of amino acids in the nervous system of ALS patients and changes in the number of excitatory amino acid receptors. ALS sera containing antibodies to L-type calcium channels and the development of immune mediated lower and upper and lower motor neuron models have revitalized research efforts focusing on an immune basis for ALS. Other pathogenic mechanisms which have been the subject of recent research include elemental toxicity, apoptosis and programmed cell death and possibly a deficiency or abnormality in growth factors. Pathogenic processes for ALS must account for an increasing incidence of ALS, male preponderance, and the selective vulnerability of the cortico-motoneuronal system. ================================================ Title : The cortical silent period and amyotrophic lateral : sclerosis. Author : Prout AJ; Eisen AA Source : Muscle and Nerve 1994 Feb;17(2):217-23 Abstract : The cortical silent period (C-SP) was elicited by transcranial magnetic stimulation in 25 normal subjects and 19 patients with amyotrophic lateral sclerosis (ALS). The inhibitory (S-X) period was highly stimulus intensity (SI)-dependent (mean r2 = 0.89 for both normals and patients with ALS). The range of the C-SP (difference between maximum and minimum S-X intervals) was age-dependent for normals (r2 = 0.701, P < 0.001) but not patients with ALS. Means, maximums and ranges for the C-SP were not significantly different between normal and ALS groups and thresholds to cortical stimulation were also comparable. There was a significant, linear, relation between the maximum C-SP and disease duration of ALS (P = 0.002). The maximum C-SP was shorter early in the disease. It is hypothesized that the reduced inhibition early in the course of ALS might reflect glutamate-induced corticomotoneuronal excitotoxicity. ================================================= Title : Abnormal acidic amino acids and N-acetylaspartyl- : glutamate in hereditary canine motoneuron disease. Author : Tsai G; Cork LC; Slusher BS; Price D; Coyle JT Source : Brain Research 1993 Dec 3;629(2):305-9 Abstract : Hereditary canine spinal muscular atrophy (HCSMA) is a lower motor neuron disease found in Brittany Spaniels that shares clinical and pathological features with human amyotrophic lateral sclerosis (ALS). Since acidic excitatory amino acids and the neuropeptide N-acetyl- aspartyl-glutamate (NAAG) are reduced in spinal cord and cerebral cortex in ALS, the levels of these substances were measured in nervous tissue in Brittany Spaniels heterozygous and homozygous for HCSMA. Significant reductions in the levels of endogenous aspartate, glutamate, N-acetylaspartate (NAA), and NAAG were found in the spinal cord in homozygous but not heterozygous HCSMA. In contrast, the activity of N-acetylated-alpha-linked-amino dipeptidase (NAALADase), an enzyme that cleaves NAAG into NAA and Glu, was significantly increased. None of these parameters was affected in the motor cortex or occipital cortex. Since NAA and NAAG are highly concentrated in motoneurons, they may play a role in the pathogenesis of motor neuron disease. == end of als 100 ==