=============================================================== == == == ----------- ALS Interest Group ----------- == == ALS Digest (#105, 08 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 == == 260+ 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 .. Editorial Comment 2 .. Re: ALS Digest hardcopy and indexes for #51-75 and #76-100 3 .. SMA Interest Group 4 .. Abstracts of papers from Dan Rosen 5 .. On-line Grief and Loss Network 6 .. recent ALS citations 7 .. HELP!! BW 1003c87 8 .. IGF-1 Myotrophin 9 .. BDNF (1) ===== Editorial Comment ========== Dear Friends, We are seeking help with a few things: Several ALS patients are at a point where they need to consider options available for tube feeding. We already have two very useful comments about tuibe feeding that were published in ALS Digest #77 ... but they would love to hear more about experiences of others (the patients wish to remain anonymous, and do not feel comfortable posting messages to the list, but they are subscribers and will see the responses). In a separate "broadcast" I will re-send the two excellent postings from #77. Please help with this request if you have information about tube feeding options. I am working on a document called "FAQ-ALS Interest Group". It is an attempt to answer frequently asked questions (FAQ) about this group. If any of you have ideas about what should be included in such a document, please let me know about them. Soon I will have completed the first draft, and will include it in a future issue. As, always ... thanks to all of you (now over 260 people) for making this a most useful and worthwhile group. rgds,bro (Bob Broedel) (2) ===== Re: ALS Digest hardcopy and indexes for #51-75 and #76-100 ========== Date : Wed, 08 Jun 94 08:01:06 MST >From : "gnicholas" To : CARROLL@wmich.edu Cc : bro@huey.met.fsu.edu Subject: Re: ALS Digest hardcopy and indexes for #51-75 and #76-100 Dear Hardy, Gee, do I owe you an apology. I am so sorry to have not sent you a copy of Vol 3. and the Index for the first 75 Digests. I do remember you, and your close proximity to my eldest child. She lives in Hartford, just to the west of you. A lot of water has gone under the bridge since I last spoke with you. I about burned out and up compiling the Index for the first 75 Digests. Whoooooweeee, what a task, but I maintained my self-imposed standards for accuracy. I drove myself much too hard, and fell off the horse. I took a long break from the compiling game, and may have let a lot of people down. I have occupied my time attempting to get an 'Advanced Prosthetics Initiative' going here at the Lab. I'm trying to put together a program which will use the problem solving skills of the National Laboratorys to answer the needs of the prosthetic user community, in materials, design, and application. This has occupied the forefront of my imagination exclusively for the last five months. Now the benighted management of my Lab has, thru indecision, just about killed what I feel is one of the major social issue problems of our time. Color me mad. In trying to get it together again, I've purchased an electronic publishing program called 'FOLIO'. This program is one of the few I was able to find that had the promise of serving multiple platforms, including DOS, WINDOWS, and MACINTOSH. I've been having minor successes with getting a DOS viewable version of Digest Volume 4 (76-100), but still am hitting the wall on exporting it for others to be able to read. I haven't had much opportunity to work with the company's tech support. I had a chart listing the 'how to' for delivery to the people who'd subscribed to my efforts, and if I didn't distribute at least Volume 3 then I must have screwed up and not put you on the chart. Please remind me how best to get the info to you, and again accept my apology for dropping the ball. Are you at the 'hold' point of the trials? My Dad has been getting the CNTF since just before Christmas, and as of today he will not receive any shots for a month. This really worries me as he really had a bad reaction to the shots. He had a daily bout with 'flu like' symptoms, and these were really wearing him out. Then he started to cough, and he coughed constantly for 16 weeks. We solved the daily 'flu' by changing the time he got the shot until the evening. He took it about 2-3 hours before his normal bedtime, and he slept thru the 'flu'. We qualified our request with the MD conducting the test prior to doing this, but what a God-send. Probably the worst point of the entire test period was when after we started the evening shots, the MD's nurse gave him a morning shot. The shots were less than twelve hours apart. He really feel apart, he was nauseous, could not sleep, had diarrhea, and generally looked like death warmed over for a week. He may really have had the flu, but we all think that the timing of the shots is what brought the problem on. We too are wondering about other drugs, or combinations of drugs currently being tested. Regards, Grant P.S. I'm send Bob Broedel a copy for his inclusion in an up coming Digest if he chooses. (3) ===== SMA Interest Group ========== Date : Tue, 07 Jun 1994 23:13:19 -0400 (EDT) >From : RICHARD SANDERS Subject: SMA Interest Group My 20 month old grandson has Spinal Muscular Atrophy (SMA). I am searching for an Interest group List similar to the ALS Interest Group where I found your name. I would be grateful for any leads. Many thanks, Richard Sanders rbsanders@delphi.com ==== == Please respond directly, because Mr. Sanders is not on the == distribution list. ==== (4) ===== Abstracts of papers from Dan Rosen ========== Date : Sun, 05 Jun 1994 07:07:34 -0400 (EDT) >From : CARROLL@wmich.edu Subject: Abstracts of papers from Dan Rosen In #100 of the ALS Digest (12 May 1994), Contents section (4), Dan Rosen says: "We have some papers in press. Do you think the netters would be interested in the abstracts of these?" I want to send a resounding "Yes!!" to this question. We are lucky to have a researcher of the reputation of Dr. Rosen participating in our network and willing to give us frontline findings about ALS research. Reading about research advances in the field is one of the best ways that I have of coping with this disease. Progress is being made!!! Thanks to Dr. Rosen and you for bringing this information to us. Keep up the good work, Hardy Carroll 618 Axtell St. Kalamazoo, MI 49008-1304 Telephone: (616) 349-5463 Email: hardy.carroll@wmich.edu (5) ===== On-line Grief and Loss Network ========== Date : Fri, 3 Jun 1994 18:05:45 -0400 (EDT) >From : Cendra Lynn Subject: On-line Grief and Loss Network ------------------------------------------------------------------ There is now an on-line information and communications system that deals with death and dying, bereavement, and major losses: both physical and emotional. In response to overwhelming need, this system was built to give physicians, hospitals, hospices, mental health professionals, funeral homes, churches, educators, and the bereaved access to this critical information. This system is designed to have informational directories and user- driven communications facilities. Rivendell Resources gathers and disseminates information about resources about death, dying, grief, bereavement, and major loss, both emotional and physical. This includes information useful to persons dealing with such loss, and to family, friends, and professionals helping them. Right now our services include: (1) an on-line resource directory of support groups, agencies, organizations, and educational activities in the U.S. and Canada (2) a general interest discussion group (3) information on the Association for Death Education & Counseling Soon to appear are: (4) an annotated bibliography of media materials, (5) special-interest highly-focused mailing lists, (6) a directory of professionals working in these fields. In the future we expect to add professional articles, research findings, and specialized discussion groups. This system is at gopher.msen.com --> Good Causes --> Rivendell Resources. The gopher server contains information on how to sub- scribe to this service. We mail update information about this system regularly as new fea- tures appear. This is a low-volume mailing list--less than once per week, probably once per month. TO SUBSCRIBE, send an email message to majordomo@mail.msen.com with the first line reading: subscribe rivendell your.email.address TO UNSUBSCRIBE, send an email message to majordomo@mail.msen.com with the first line reading: UNSUBSCRIBE rivendell your.email.address =================================================================== Cendra (ken'dra) Lynn, Ph.D. Rivendell Resources cendra@rivendell.org PO Box 3272, Ann Arbor, MI, 48106-3272 313 / 761-1960 Grace happens ==================================================================== (6) ===== recent ALS citations ========== =============================================== Title : Cytotoxicity of immunoglobulins from amyotrophic : lateral sclerosis patients on a hybrid motoneuron : cell line Author : Smith R.G.; Alexianu M.E.; Crawford G.; Nyormoi O.; : Stefani E.; Appel S.H.; Source : 1994 91/8 (3393-3397) PNASA Proceedings of the : National Academy of Sciences of the United States : of America Abstract : Patients with amyotrophic lateral sclerosis possess : antibodies (ALS IgGs) that bind to L-type skeletal : muscle voltage-gated calcium channels (VGCCs) and : inhibit L-type calcium current. To determine whether : interaction of ALS IgGs with neuronal VGCCs might : influence motoneuron survival, we used a motoneuron- : neuroblastoma hybrid (VSC 4.1) cell line expressing : binding sites for inhibitors of L-, N-, and P-type : VGCCs. Using direct viable cell counts, quantitation : of propidium iodide- and fluorescein diacetate-labeled : cells, and lactate dehydrogenase release to assess : cell survival, we document that ALS IgG kills 40-70% : of cAMP-differentiated VSC 4.1 cells within 2 days. : ALS IgG-mediated cytotoxicity is dependent on : extracellular calcium and is prevented by peptide : antagonists of N- or P-type VGCCs but not by : dihydropyridine modulators of L-type VGCCs. : Preincubating IgG with purified intact L-type VGCC or : with isolated VGCC alpha1 subunit also blocks ALS IgG- : mediated cytotoxicity. These results suggest that : ALS IgG may directly lead to motoneuron cell death : by a mechanism requiring extracellular calcium and : mediated by neuronal-type calcium channels. =============================================== Title : Sun exposure and amyotrophic lateral sclerosis Author : Steiner I.; Birmanns B.; Panet A.; Source : 1994 120/10 (893) AIMEA Annals of Internal Medicine (7) ===== HELP!! BW 1003c87 ========== Topic 1357 HELP!! BW 1003c87 bionet.neuroscience 7:57 pm Jun 2, 1994 chingwen@PURCCVM.BITNET) Hi! Dose anyone out there know where or how can I order the BW 1003c87 which is a glutamate release inhibitor and sodium channel blocker? Thanks and appreciate for your information!!!! Amy my e-mail address is chingwen@vm.cc.purdue.edu (8) ===== IGF-1 Myotrophin ========== CEPHALON, INC. (COMPANY REPORT) TS=CEPH KEMPER SECURITIES GROUP, INC.: Pandya, B., et al 03-23-94 8 Pages Includes Abstract (March 23, 1994) Cephalon, Inc. is a biotechnology company whose research and development programs are focused towards development of novel therapeutics for the treatment of neurological diseases. The company is utilizing the technologies of molecular biology as well as medicinal chemistry to develop drags for the treatment of the following clinical indications: Lou Gehrig's disease, or amyotrophic lateral sclerosis (ALS), Alzheimer's disease, stroke, narcolepsy, various kinds of peripheral neuropathies, prostate cancer and head and/or spinal injuries. Myotrophin in pivotal trials for ALS Insulin-like growth factor-1 (IGF-1) or Myotrophin, the product most advanced in Cephalon's product pipeline, is currently in a pivotal Phase II/III trial in both North America and Europe. The company is developing Myotrophin for the treatment of ALS, which involves slowly progressing degeneration of motor neurons that eventually results in the patients' death from the loss of control of respiratory muscle. In preclinical trials, Myotrophin has been shown to promote prolonged survival of neurons and promote sprouting of axons of neurons. If Myotrophin stands up to its promise, we expect Cephalon to market the drug, together with its joint venture partner, Chiton, in early 1996 and achieve profitability in 1997. Status of Pivotal Clinical Trials of Myotrophin in ALS patients ALS is a fatal disorder involving a slowly progressing degeneration and death of motor neurons. In most ALS patients the disease progresses from diagnosis to death in a period of approximately three to five years. The patients die as a result of loss of control of respiratory muscles that results in the inability to breathe. It is estimated that there are approximately 25,000-30,000 ALS patients in the United States and approximately 40,000 patients in Western Europe. Myotrophin, or recombinant human insulin-like growth factor-1 (rhIGF-1), is a neurotrophic factor that has been shown to promote survival of motor neurons and enhance regeneration of damaged motor neurons. Thus, Myotrophin is likely to promote survival of degenerating motor neurons in ALS patients. Cephalon initiated a Phase II/III clinical trial of Myotrophin in approximately 200 ALS patients in the United States in January 1993. As of early March 1994, the enrollment of ALS patients has been completed. Therefore, we expect that the results of the trial will be available by the end of 1994. In October 1993, the company initiated a Phase II/III clinical trial of Myotrophin in patients with ALS in Europe. The European trial is expected to be very similar to the one in the United States in that it will have a three-month base line evaluation of the patients and a subsequent nine-month treatment period. We expect that the patient enrollment will be completed within the next three to six months. The European Phase II/III clinical trial of Myotrophin in ALS patients will support product approval applications in European countries. Additionally, the European trial may be used as a second well-controlled pivotal study to support the new drug application (NDA) in the United States. In other words, Cephalon will be in a position to submit results of two pivotal clinical trials to support its NDA with the FDA. Table 2 - Developmental Milestones 1994-96 Milestones Est. Timing Initiation of phase III clinical trials for Modafinil in the treatment of narcolepsy 2Q 1994 Filing of IND application for Myotrophin in the treatment of post-polio syndrome 2Q 1994 Formation of a corporate partnership for the 2Q 1994 development of receptor tyrosine kinase (RTK) antagonists for the treatment of prostate cancer Initiation of clinical trials of Myotrophin in the 3Q 1994 treatment of chemotherapy-induced peripheral neuropathies Filing of IND application for RTK antagonists for prostate cancer 4Q 1994 Progress Report on ALS clinical trials 4Q 1994/ 1Q 1995 Filing of NDA for Myotrophin use in ALS 1Q 1995/ 2Q 1995 Filing of NDA for Modafinil in the treatment of narcolepsy 4Q 1995 Filing of IND application for CEP-075 for head/spinal injury 1995 Filing of IND application for calpain inhibitors for stroke 1995/1996 Approval for Myotrophin use in ALS 1Q 1996/ 2Q 1996 Filing of IND application for APP inhibitors/NEMS for Alzheimer's Disease 1996 ==== == Cephalon, Inc. == 145 Brandywine Parkway == West Chester, PA 19380 == TEL 215-344-0200 == FAX 215-344-0065/215-344-0649 ==== (9) ===== BDNF ========== SUMITOMO PHARM., U.S. FIRM LINK ON DRUG RESEARCH OSAKA, JUNE 8 (JIJI PRESS)--SUMITOMO PHARMACEUTICALS CORP. SAID WEDNESDAY IT HAS SIGNED A FIVE-YEAR CONTRACT WITH U.S. BIOTECHNOLOGY FIRM REGENERON PHARMACEUTICALS INC. FOR A JOINT RESEARCH AND DEVELOPMENT PROJECT ON BRAIN-DERIVED NEUROTROPHIC FACTOR. UNDER THE CONTRACT, THE DRUG MAKER BASED IN THIS WESTERN JAPAN CITY WILL DISBURSE UP TO 25 MILLION DOLLARS FOR THE PROJECT WITH THE TARRYTOWN, NEW YORK-BASED FIRM. APPLICATION OF BDNF, PROTEIN THAT CAN BE FOUND IN THE BRAIN, HAS BEEN EYED FOR THE TREATMENT OF AMYOTROPHIC LATERAL SCLEROSIS, ALZHEIMER'S DISEASE AND OTHER DISORDERS OF THE PERIPHERAL AND CENTRAL NERVOUS SYSTEMS, SINCE IT PROVIDES LIFE SUPPORT FOR NERVE CELLS IN THE NERVOUS SYSTEMS. REGENERON IS ALREADY IN THE SECOND PHASE OF CLINICAL TESTING OF BDNF FOR AMYOTROPHIC LATERAL SCLEROSIS. SUMITOMO PHARMACEUTICALS HOPES TO START PRECLINICAL STUDIES IN JAPAN SOON AND BEGIN CLINICAL TESTING AS EARLY AS 1995, SAID THE OSAKA COMPANY, 75 PCT OWNED BY SUMITOMO CHEMICAL CO. REGENERON WAS SET UP IN 1988 WITH THE AIM OF DEVELOPING A CURE FOR CRANIAL NERVE DISEASES AND HAS SUCCEEDED IN DEVELOPING TECHNOLOGY FOR MASS PRODUCTION OF BDNF THROUGH GENE RECOMBINATION. .END ==== == Regeneron Pharmaceuticals, Inc. == 777 Old Saw Mill River Road == Tarrytown, NY 10591-6707 == TEL 914-347-7000 == FAX 914-347-2113/914-347-2815 ==== == end of als 105 ==