Date: Sat, 16 Dec 95 03:05:57 EST From: Bob Broedel To: als@huey.met.fsu.edu Subject: ALSD230 ALS-ON-LINE =============================================================== == == == ----------- ALS Interest Group ----------- == == ALS Digest (#230, 16 December 1995) == == == == ------ Amyotrophic Lateral Sclerosis (ALS) == == ------ Motor Neurone Disease (MND) == == ------ Lou Gehrig's disease == == ------ maladie de Charcot == == == == 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 == == 1320+ 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 == =============================================================== == Back issues of the ALS Digest are available on-line at: == == http://http1.brunel.ac.uk:8080/~hssrsdn/alsig/alsig.htm == =============================================================== == A full set of back issues (on MSDOS 3.5 INCH HD diskette) == == are available by sending me your full mailing address. == == They are free-of-charge. International requests welcome. == =============================================================== CONTENTS OF THIS ISSUE: 1 .. a "treatment" inquiry 2 .. lumps and swelling 3 .. etiology ALS 4 .. Going fishing 5 .. research news 6 .. BDNF 7 .. A Patient's Guide to ALS 8 .. ALS Guide Part 1 - What is ALS? (1) ===== a "treatment" inquiry ========== Date : Tue, 5 Dec 1995 06:35:07 -0800 >From : gimleu@ix.netcom.com (Michael Mazquiaran) Subject: Re: ALSD228 ALS-ON-LINE This is an inquiry about a certain treatment that is being offered to my daughter, an ALS patient. The treatment consists in removing all of her teeth fillings on the premise that those fillings supposedly contain mercury. I want to know if anyone has submitted to that treatment and if there is any merit to the claims made by the people that are selling that "treatment" This "treatment" does not come cheap. They charge $1,000 per each filling plus many other charges. To me it smells like a scam, but it is too difficult to say so to my daughter, and specially when I have no other basis for saying so that my own feelings about the matter. I'll appreciate any help anyone can give me. Sincerely, Michael Mazquiaran 3620 SW 108 Ave Miami, Fl 33135 Tel: 305-227-8410 305-448-6495 (day time) gimleu@ix.netcom.com (2) ===== lumps and swelling ========== Date : Wed, 13 Dec 1995 08:41:01 -0600 >From : frankfather@cs.bgsu.edu (Cathy Frankfather) Subject: Re: ALERT-ALS-RILUTEK I have greatly appreciated this newsletter. My Mom has progressive bulbar palsy and the info here helps a great deal. I was wondering though if anyone else is getting theses lumps and swellings around the neck-shoulder area, also the back of the neck, and face. I don't understand what these are, if anyone could help with this I would be most grateful. Thank You Cathy Frankfather (3) ===== etiology ALS ========== Date : Wed, 13 Dec 1995 10:41:55 EST >From : pbutterworth@topcat.bridgew.edu Subject: etiology als I am looking for any help that can be provided. I am currently working on a research paper that is focused on three different neurological problems. One of which is ALS. Any information that could be sent regarding etiology, and/or any significant correlations that you may have encountered with ALS would be greatly appreciated. pbutterworth@bridgew.edu (4) ===== Going fishing ========== Date : Tue, 12 Dec 95 09:50 PST >From : Brent Peters Subject: Going fishing I've had ALS for couple years and want to head for the bush again. Down on the B.C. coastal waters probably. Somewhere fairly remote, lots of wildlife. What I had in mind was to set up a camp, float camp, whatever. Someplace to hide out that's easy on the head. There are probably others thinking the same thing. I think this ALS may be partly some kind of a mental and enviromental problem. Anyhow I want to get out of town and want others, that like the outdoors, to come along. I've a few resources ( 32' boat that was still floating last time I saw it, truck, some camp gear ) but will need afair bit of help setting up, running supplies,fire wood cutting, some kind of lease from the B.C. gov., and someone able bodied to stick around. So anyone interested drop a line. (5) ===== research news ========== TITLE : Unscrambling Lou Gehrig's Disease Gene; Research: The latest : finding shows it causes the illness. Now, scientists are seeking : to figure out how it acts to learn about what causes the non- : inherited version of the crippling disease. BYLINE : MALCOLM RITTER CREDIT : ASSOCIATED PRESS DATE : 11/12/95 SOURCE : Los Angeles Times When scientists announced in 1993 that they had identified a flawed gene that causes Lou Gehrig's disease, they faced a critical question: Is it a saboteur or a loafer? More precisely, does the gene cause the disease by actively making trouble or by simply failing to do its normal job? It wasn't just an academic issue. If the gene was failing to provide the body with a crucial protein, maybe a medicine could supply the protein instead. In fact, since the gene normally produces a substance that detoxifies harmful oxygen-free radicals, the finding suggested that taking other "antioxidants" might help treat the disease. But now the scientific verdict is in: The gene is a saboteur. So the notion of simply replacing a missing antioxidant is out the window. And scientists are scrambling to figure out just how the flawed gene causes trouble. The gene itself actually accounts for only about 2% of the nation's 5,000 new cases per year of the disease, often called Lou Gehrig's disease for the New York Yankee who died of it in 1941. In fact, only 10% of cases appear to come from inheriting any single flawed gene. But scientists hope that learning how the recently discovered gene causes trouble will help reveal what causes the far more common non-inherited version. < parts deleted > In 1993, researchers announced that some inherited cases were caused by flaws in the gene that tells the body how to make a protein called copper- zinc superoxide dismutase, or SOD1. More than 35 disease-causing flaws are now known in this gene. But how do they cause ALS? It's a mystery, but scientists have taken some first steps toward finding out, says Dr. Robert Brown of Massachusetts General Hospital, one of the scientists who made the 1993 announcement. A key finding is that the problem is not a lack of normal SOD1 protein, he said. So the question is what the mutant protein is actively doing to cause disease. One possibility is that it is unusually susceptible to a particular mis- behavior, putting chemical tags on other proteins that should not have them, said Joe Beckman, a professor of anesthesiology at the University of Alabama at Birmingham. Those tags might keep those proteins from doing their jobs, crippling the nerve cells and causing ALS, he said. Even normal SOD1 occasionally tags other proteins if it is exposed to unusually high levels of a substance called nitric oxide, he said. In fact, Beckman suspects ALS in general may be caused by overproduction of nitric oxide. The mutant SOD1 protein may just start misbehaving in response to a lower level of nitric oxide than regular SOD1 does, he said. Beckman said he has evidence that mutant SOD1 protein puts tags on a protein that normally doesn't have them, and which appears to play a key role in nerves that control muscle. He declined to discuss details of the work, saying it had not yet been accepted for publication in a scientific journal. There are other proposals for how the flawed protein misbehaves. Brown said he is interested in the possibility that the mutant protein clumps together abnormally, somehow poisoning nerve cells. Or maybe the mutant protein lets its copper and zinc atoms escape, and it's the metals that are toxic. So what does all this mean for finding a new treatment? Brown is optimistic, saying each new hypothesis raises its own new ideas for therapy. Scientists have created mice that show an ALS-like disease, which should allow for rapid testing of possible treatments, he said. But until researchers find out how the flawed gene causes ALS, he admits, "we probably are not going to be too far ahead in treating the illness." (6) ===== BDNF ========== CANCER BIOTECHNOLOGY WEEKLY Monday December 11, 1995 Dr. Leonard S. Schleifer, president and CEO of Regeneron Pharmaceuticals, Inc., Tarrytown, New York, spoke at the Robertson Stephens & Company 1995 Medical Conference held in New York City. He announced several new scientific developments, including: The Phase III clinical trial of brain-derived neurotrophic factor (BDNF) for amyotrophic lateral sclerosis (ALS, commonly known as Lou Gehrig's disease) being conducted by Amgen Inc. on behalf of Amgen-Regeneron Partners is now over 90 percent enrolled. < parts deleted > Schleifer stated that patient enrollment in the BDNF Phase III clinical trial began in July 1995. The Phase III trial is a double-bind, placebo-controlled, 38-center study in over 1,000 patients, who will be treated for nine months. < parts deleted > "We are working with Amgen to move the development of BDNF forward aggressively," said Schleifer. "BDNF appears to be safe and well tolerated, and it may have unique therapeutic benefits for ALS patients." < parts deleted > Further BDNF and NT-3 Development Amgen-Regeneron Partners, a general partnership equally owned by Amgen and Regeneron, is developing BDNF and NT-3 in the United States. Outside the United States and Japan and certain other Pacific Rim countries, Regeneron has granted Amgen a license to BDNF and NT-3. < parts deleted > Regeneron is also collaborating with Sumitomo Pharmaceuticals Company, Ltd. to develop BDNF in Japan. < parts deleted > The company's technological expertise in protein growth factors, their receptors, and their mechanisms of action has been and continues to be utilized in the discovery and development of neurotrophic factors for the potential treatment of neurodegenerative diseases, peripheral neuropathies, and nerve injury. More recently, Regeneron has used these technologies to attempt to identify treatments for diseases and conditions outside of the nervous system, such as cancer, muscle disease, and angiogenesis (blood vessel growth). (7) ===== A Patient's Guide to ALS ========== Date : Sat, 9 Dec 1995 16:46:03 -0600 >From : jacobson@phoenix.net (Doug Jacobson) Subject: A Patient's Guide to ALS on the Web I wanted to inform the group that I have put a document on the Web entitled "A Patient's Guide to ALS". It was written by Dr. D. Eric Livingston, a 38 year old physician who was himself recently diagnosed as having ALS. I would like this to be a living document, and if anyone can offer additions or corrections, I will incorporate them gladly. The page is at: http://www.phoenix.net/~jacobson/als1.html Dr. Livingston can be reached at PALSMD@aol.com. As we continue to look with hope toward tomorrow, I would like to wish everyone who reads this a joyous Holiday Season! God bless you all! Doug Jacobson jacobson@phoenix.net Kicking ALS butt one day at a time... **************************************************************** * Doug Jacobson Proud to be a Parrothead! Follow the * * E-mail: jacobson@phoenix.net dancing life... * * Web: http://www.phoenix.net/~jacobson * **************************************************************** ==== = Thanks Doug. For the benefit of subscribers who do not have WWW = access, Dr. Livingston's document will be also published here in the = ALS Digest. The first part follows this note. The second part will = make up ALS Digest 231. The remaining parts will be in 232. rgds,bro ==== (8) ===== ALS Guide Part 1 - What is ALS? ========== Date : Thu, 7 Dec 1995 15:55:55 -0500 >From : PALSMD@aol.com Subject: ALS Guide Pt1 - What is ALS? ALS A Guide for Patients by D. Eric Livingston, M.D. Internet: PALSMD@aol.com I am a 38 yr old Physician. During a ski trip to Colorado in February '95, I noticed some mild weakness. In March I was diagnosed with ALS. I had been practicing medicine for about 7 years. My understanding of ALS was limited because it's fairly uncommon and I'd never encountered a patient with the disease. I have since read and learned more about it. Unfortunately, I found that helpful information wasn't always easy to find. As a result I put together a single source of information and resources on ALS, primarily written for newly diagnosed patients and their families. Through sharing information we can make living with ALS as comfortable as possible. I've tried to create a practical source of information under the following five topics: "What is ALS?," "Practical Tips," "Organizations & Resources," "Drugs" & "Treatment Centers." It is important that you realize I am not an expert on ALS. I am a patient with a medical background which offers some advantages to interpreting available information. I wish to avoid giving an specific medical advice. That is something best left between you and your doctor. I do hope to pass along some information that will help you get the most out of all the medical resources available. Please first discuss any changes that you may wish to make as a result of reading this with your doctor. I'm sure many PALS (Person(s) with ALS) and their families have a tremendous body of knowledge and experience to share. I encourage you to look into the online ALS Bulletin Boards and services, as an excellent format to share and exchange information. WHAT IS ALS? Amyotrophic Lateral Sclerosis, (aka ALS, Lou Gehrig's Disease, Motor Neuron Disease, Charcot's Disease), is a neurological disease affecting the nerves that supply all voluntary muscles. ALS was first identified in 1874 by a french doctor named Charcot. It is one of the most devastating diagnoses to receive. There is no known cure and, until recently, no medical treatment that could alter the course of this disease. Fortunately, we now have one drug shown to extend the survival of some ALS patients, Riluzole (Rilutek), as well as several other drugs being investigated. ALS is a very uncommon disease, affecting about 1 per 100,000 each year. It more often affects people over age 40, men slightly more than women. The usual cause of death is through respiratory complications. Survival time, as well as the course of the disease (the order in which symptoms develop) varies widely. Historically, from textbooks, ALS has an average survival time of 3 to 5 years, with about 20% of those affected living past 5 years. The classic "Progressive Bulbar Palsy" variant has a survival time of 1 to 3 years. Let me state clearly that there are a lot of reasons not to get caught up with numbers on survival time. First, those numbers are averages based on thousands of people and that doesn't tell us, as individuals, how we'll do. Every individual's course is different. Second, there are documented cases of spontaneous remission and long term ALS survivors. Third, with the availability of gastrostomy feeding tubes, home ventilators, etc, not only length of survival, but quality of life can be extended. Finally, it's far too early to tell what impact these new research drugs, (and others to follow), will have with early and long term treatment. Also, I firmly believe that state of mind influences survival time. I'll comment more on that under "My Personal Philosophy" at the end of "Practical Tips." ALS affects the muscles of arms, legs, posture, face, tongue, speech, swallowing, and eventually, breathing. It may also affect emotion, resulting in periods of inappropriate or exaggerated emotional responses. What it does not affect is thinking or intelligence, sensation/sense of touch, taste, smell, hearing, sight, eye movement, involuntary muscles of the heart, bowel, bladder, or sexual function. Regarding the disease process, there are 2 types of motor nerves that supply voluntary muscles; both are affected in ALS. One type are called Upper Motor Neurons (UMN's). These begin in the brain and extend into the spinal cord. When these nerves are affected, the result is spasticity, weakness and over- reactive reflexes. The second type are called Lower Motor Neurons (LMN's). These begin where UMN's end (in the Anterior Horn Cell region of the spinal cord), and each travels to a specific muscle. When these are affected, the result is marked weakness leading to paralysis, muscle wasting and diminished to lost reflexes. As these nerves become dysfunctional you may see muscle fasciculations. When symptoms begin in the arms or legs it may be referred to as "Limb Onset ALS." To make matters a little more complicated, there is a special subset of nerves that come directly from the brainstem and control specialized functions like speech and swallowing. When symptoms arise from these nerves they may be referred to as "Bulbar" symptoms. Bulbar is a traditional term for brainstem. A diagnosis of ALS is made by "Clinical Diagnosis." This means that no single test can prove the diagnosis. Instead, it requires a thorough exam and many tests, sometimes over a period of weeks, all of which need to be interpreted by an experienced neurologist in order to confirm or reject a diagnosis. The two currently identified forms of ALS are "Sporadic" and "Familial." The most common type is "Sporadic ALS," accounting for over 90% of the cases of ALS. Here the cause is unknown and may affect anyone at random. "Familial ALS" accounts for the remaining cases (<10%) and is caused by inheriting a dominant gene from one parent. In this case, there would be a family history of ALS among blood relatives and also a 50/50 chance of the affected person passing it onto their children. If neither parent or other blood relatives have ALS, you'd expect to have the Sporadic form and, therefore, not expect to pass it onto your children. Presently there is no blood or genetic screening test to detect "the ALS gene" for all familial forms of ALS, but, there is a test for the chromosome 21 defect. However, only approximately 20% of the people who have familial ALS have this defect. These studies are designed for research, & aren't yet available for general testing. It takes months to get results & there can be problems with the tests, (ie. unreadable.) For information call ALSA at (800)-782-4747 or the Les Turner Center (708)-679-3311. Definitions Amyotrophic - 'A' means "Without," 'Myo' means "Muscle," 'Trophic' means "Nourishment" Lateral (or Lateralizing) - Refers to uneven development of symptoms between right & left sides Sclerosis - Refers to "destruction" or "disease" of tissue Fasciculations - Small, involuntary, visible contractions of individual muscle fibers PALS - Person with ALS Neuron - Nerve cell FDA Drug approval process Years 1-2 Preclinical testing in lab & on animals Years 3-5 Human Clinical testing to determine safety & dose (Phase I) Years 6-7 Controlled testing to determine efficacy, 1-300 (Phase II) Years 8-9 Extensive testing to confirm results, 1-3,000 (Phase III) Years 10-11 New drug application Year 12 FDA Final Approval, available for prescription === end of als 230 === ALS Association (National Office) 21021 Ventura Boulevard, Suite 321 Woodland Hills, CA 91364 USA TEL 818-340-7500 FAX 818-340-2060 TEL 800-782-4747 (Patient Hot Line) E-M eajc27b@prodigy.com ALS Society of Canada 220 - 6 Adelaide Street East Toronto, Ontario, M5C 1H6 CANADA TEL 416-362-0269 TEL 800-267-4ALS (toll-free in Canada) FAX 416-362-0414 E-M alssoc@inforamp.net