Date: Mon, 6 Nov 95 13:59:27 EST From: Bob Broedel To: als@huey.met.fsu.edu Subject: ALSD222 ALS-ON-LINE =============================================================== == == == ----------- ALS Interest Group ----------- == == ALS Digest (#222, 06 November 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 == == 1180+ 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 .. Editorial 2 .. Help Request from China 3 .. ALS Documentary 4 .. 6th International Symposium on ALS/MND in Dublin, and more ... 5 .. Where to begin? 6 .. ALS, cough and saliva production 7 .. Riluzole 8 .. Myotrophin (1) ===== Editorial ========== There is a lot of information, new people signing up, and many messages to post. And help is on the way, in that a new LISTSERV called ALSconnect will be starting soon. The next issue of ALS Digest comes out in a couple of days. Sincerely, Bob Broedel (2) ===== Help Request from China ========== >From : wanglei@csnetlib.pku.edu.cn (Wang Lei) Subject: For HELP Date : Mon, 6 Nov 95 2:22:09 BJT HELP! HELP! If you can give me some advice, please mail to wanglei@csnetlib.pku.edu.cn I am a graduate student in Peking University, China. My uncle had illness for many years. All our families are worried about it, but we have no very efficient way for treatment. Now my university enters the INTERNET. So I mail this letter to you for help. No matter what you think about it, thanks a lot for your concerning. Mr. Zhang, male, 50-year-old, Ht 1.65m, Wt 56 kg, has experienced weakness in his lower extremities for 5 years with known NIDDM for 8 years. In 1987, NIDDM was dignosed, then Clibenclamide,Phenformin Hydrochloride and some Chinese herbs were given, but his conditions fluctuated. In 1990, he began to experience limp in the right leg and rigidity of knee when it was cold or he was excited. Gradually he felt that his two legs were weaker and weaker, accompanied by rigidity of the knees, muscle fasciculation, spasm and slight muscle atrophy of the two legs. Although it is inconvinient for him to move around, he went to many famous hospitals in big cities, such as Beijing and Dalian, with the help of his family. The additional examinations are belows: CT of spine: The edges of the vertebral bodies and articular processes have small spurs. Spinal stenosis of L4 with diameter 1.2 cm. The rest spinal canals are normal. CT of brain: The density of matter is normal. Ventricle, cistern and sulci are normal. Doppler of brain is normal. BAEP is normal. Myogram : Damage is not neuropathic and myopathic in nature. Cervical MRI (coronal and sagittal planes):Posterior intervertebral disc protrusion compresses duramater. Posterior longitudinal ligment is hyper- trophy below C6 level. Cervical vertebral alignment is normal. Signal of spine cord is normal. PE : Muscle strength of the two legs are IV. Tendon reflexes are active in the legs. Sensation is normal. Diagnosis : Primary Lateral Sclerosis. Lateral Sclerosis Syndrome. Neuropathy and Myopathy of DM. He has has neural nurishments (ATP,COA,VitC,VitB,...), some herbs, acupuncture and massage for two years; but his conditions are getting worse and worse. It is very kind of you to give us some advice for diagnosis and treatment. Thanks a lot. My email address: wanglei@csnetlib.pku.edu.cn (3) ===== ALS Documentary ========== Date : Wed, 1 Nov 1995 20:23:06 -0500 >From : Ruvkun@aol.com Subject: ALS Documentary My name is Robert Ruvkun, and I am a Graduate Student in Film at San Diego State University. As my final project, I am producing a documentary about ALS. My interest in the subject stems from a former girlfriend (now in medical school at The University of Washington) who used to be an attendant to two ALS patients. Specifically, I am in search of several families who are willing to participate as the subject of the film, and how you cope with the disease on a daily basis. However, I am looking to communicate with as many families as possible. Anyone interested in the film can contact me at: Robert Ruvkun 302 N.72nd Seattle, WA 98103 (206)706-1098 Home (206)343-4617 Work E-mail: Ruvkun@aol.com The project does not demand that I live in San Diego, so I am currently living in Seattle working for The Seattle Mariners Baseball Club. Thank you for your time. If you have any questions, please e-mail me or call. (4) ===== 6th International Symposium on ALS/MND in Dublin, and more ... ========== Date : Wed, 1 Nov 95 10:57:52 GMT >From : a-furley@nimr.mrc.ac.uk (Andy Furley) Subject: Re: ALSD221 ALS-ON-LINE Dear Bob, First, thanks for carrying on the good work. You may be gratified to know that the ALS Digest was highly commended in a talk by Dr Andrew Feenberg at the recent 6th International Symposium on ALS/MND in Dublin, Ireland from which I have just returned (of which more below). He was particularly impressed that the Digest seemed to regulate itself in terms of the scientific basis of its content, presumably due to the broad background of its subscribers. Since this is my third contribution, I am long overdue for an introduction. I am an academic scientist interested in the embryological development of the nervous system, particularly the way in which nerve cells make their initial connections (so-called axon guidance). With an irony that I don't like to reflect upon, I find that my professional and personal interests have converged; my father, 75, was diagnosed with MND in June of this year. So far he is doing well and suffers only from a general weakness and some loss of manipulative skill. He is currently being treated with riluzole, provided generously by Rhone Poulenc on a compassionate use basis. My purpose here is threefold: 1) I would be happy to write up a summary of the Dublin meeting, which was very exciting and informative, if this is not already being done by other subscribers. I have to say, however, that I am somewhat daunted by the task of trying to summarise the clinical trial data, particularly given how important this is to the ALS Digest community and how sensitive companies and investors are to information presented in this forum. Therefore I would be happy to collaborate to write up the meeting with other subscribers who attended the meeting, particular a professional with experience in judging clinical trial data (which I am certainly not). 2) I have immediate comment on the letter from Dick Price (ALSD221) proposing to set up an Internet home page. This is a great idea and should be encouraged. However, Dick should know that Dr Andrew Feenberg (see above) is also in the process of doing this, so perhaps the two parties should get together and co-ordinate. I don't have an E-mail address for Dr Feenberg, but he is an ALSD subscriber so you (Bob) should have it. Otherwise, he is at the Department of Philosophy (!), San Diego State University, San Diego. Don't forget to include access to the UK-based ALSD archive run by Stuart Neilson (stuart.neilson@brunel.ac.uk) CSHSD, Brunel University (http://http2.brunel.ac.uk:8080/~hssrsdn/). If it could be co-ordinated with the Prodigy-based ALS group (which I have only just heard about through Dr Feenberg), then all the better. 3) Yet again ALSD221 contains references to insult or injury (be it physical, chemical or pathogenic) preceding ALS onset (letter from R. Broden). My father had major surgery in the year or so preceding onset of MND, and in fact may have had some sort of fit while recovering from anaesthetic (something I am investigating in more detail. Hopefully I will have more to say in a future contribution). This prompts me to report one potentially exciting observation that was made at the ALS/MND symposium. Much attention was focused on the role of superoxide dismutase (SOD1) in ALS/MND. In particular, much effort is directed toward making mouse models of FALS using transgenic SOD1 animals. In addition, Cephalon have made a "knockout" SOD1 mouse, which means that the gene has been genetically deleted and so SOD1 enzyme is not made in this mouse strain. Apparently these mice are born normal and mature normally without any evidence of motor neuron disease. However, some of the mice seem to develop the disease "in response to injury". Since this information derives from a comment made at the end of an SOD1 talk, I do not have any further detail of what "injury" means in this case, nor can I comment on the reliability of the comment. However, if true, this would suggest that this mouse may provide a model system to look at the effects of various physical, chemical or pathogenic insults on the onset of motor neuron disease and so help us understand what environmental elements may be involved in the onset of the human disease. A very exciting prospect I think. All the best, andy Andrew J.W. Furley, Ph.D. Developmental Neurobiology National Institute for Medical Research The Ridgeway, Mill Hill LONDON, UK-NW7 1AA Tel. +44 181 959 3666 x2252 Fax. +44 181 913 8536 or 906 4477 ===== = Sorry, but I can not figure out which e-mail address belongs to = Dr. Feenberg. rgds,bro ===== (5) ===== Where to begin? ========== >From : bayeta@iastate.edu Subject: Where to begin? Date : Mon, 30 Oct 1995 22:17:34 CST Five years ago, my mother began to lose the use of her legs. It was getting harder and harder for her to walk, and the doctors couldn't tell her what was wrong with her. After a while, they diagnosed her as having Charcot Marie Tooth, and gave her braces...but her legs kept on degenerating. We all thought it was Carcot Marie Tooth, until she had to be hospitalized last Thanksgiving because she was beginning to not be able to breathe freely. Within the five years, the braces evolved into a walker, a wheelchair, and finally, a motorized wheelchair. At this point, we began to think it was something more than CMT. My mother visited the MDA facility in Houston, Texas, and after several tests, they sent her back home. I spoke with one of the doctors, and they told me her diagnoses was "a motor neuron disease--but not necessarily ALS." The doctor went on to tell me that there is no biological marker for ALS, and it really can't be confirmed until after death. When we heard this, my family was at a loss of what to do. I have several questions: 1.) Is there a way to definitely diagnose ALS? 2.) Are there other disease that mimic ALS, maybe even Motor Neuron Diseases, but are more managable (maybe even curable?) 3.) Is there any medication she can take? She's currently not taking anything at all. 4.) Does anybody know of any good doctors that specialize in this field in the Dallas/Fort Worth area? 4.) Where do we go from here? All of the literature that I've read has been bleak--I'd like to be proactive, but I don't have any idea if this is what she really has-- Her symptoms are progressive wasting of muscle, slight tremors, and she has trouble breathing at night--she has to use a bipap to get decent sleep...but the onset seems really slow and extremely gradual...and if it was ALS all along, why was it so hard to diagnose? She has run the gamut of testing, and there doesn't seem to be anything conclusive. I realize that all these questions may be difficult to answer, but I feel like we have no other place to go to for help. I would appreciate any feed back that other digest readers might have for me. Please email me privately at gbb@iastate.edu, so as to not bombard the digest with extraneous mail. Thank you all in advance for your answers, and for the availability of this wonderful resource. Gail Gbb@iastate.edu (6) ===== ALS, cough and saliva production ========== Date : Mon, 23 Oct 1995 15:20:01 +0100 >From : Marco Montaruli Subject: ALS, cough and saliva production Hello everybody. I hope someone will be able to answer a few questions. My brother in law, 39, was diagnosed ALS in 1993. He reports since a few weeks a new very troublesome symptom: his production of saliva increased consistently, accompanied by frequent cough and catarrh. Saliva itself seems to be denser than normal. All this makes him weary, giving sometimes a sense of panic. He'd like to know if there could be any relations between these simptoms and his bulbar origin of ALS; in other words, is this typical of his type of ALS? Is it a normal consequence? More, can it be related with food (he actually has an almost totally vegetarian diet, as free of pesticides as possible) or with any chemical element (missing or too present)? Could be this a self-defence of the organism against something ingested? Finally, he is treated with acupuncture: any comments on this? Thank you for any help. I'm very proud to be a member of this list, which is itself a major reason for the existence of the Internet. _____________________________________________________________ Marco Montaruli, General Plastics - Rome (7) ===== Riluzole ========== Date : 29 Oct 95 19:53:33 EST >From : KENT LEE WOODMAN <71043.2035@compuserve.com> Subject: Riluzole Don't know if the following information has been presented in quite this direct format. Help yourself if it does not repeat. Called Rhone-Poulenc Rorer and spoke at length with agent there (610-454-3872) last week. Asked what progress was made and where they were and how to get in line for dosages. They reiterated that the final hurdle at FDA has been taken, with the committee voting DO recommend several weeks ago. This is the last step, and they anticipate final approval and the all important labeling content information from FDA and a big press conference within 4 weeks. They are gearing up to make Riluzole internationally, and sensitive to the press of other pharmalogical firms recently on geographical pricing, will make a "world price" for the drug for everyone. You may recall that tests utilized two (2) each 50 mg tablet doses/day. That's about the size of a large aspiring tablet. In the news release will be an 800 number for the firm with which they are contracting for distribution sales. Upon receipt of your doctor's prescription, they will SHIP DIRECT TO THE HOME/OFFICE OF THE PATIENT! Man, it's starting to get interesting. What with another step with in the process with Myotrophin, can simultaneous multiple drug testing be far behind? Cheers from Alaska! -klw- (8) ===== Myotrophin ========== CEPHALON AND CHIRON REPORT SUCCESSFUL SECOND STUDY OF MYOTROPHIN; EUROPEAN DATA CONFIRM BENEFICIAL EFFECTS OF MYOTROPHIN IN ALS WEST CHESTER, Pa., Oct. 31 /PRNewswire/ -- Cephalon, Inc. (Nasdaq: CEPH) and its partner, Chiron Corp. (Nasdaq: CHIR), announced today that findings from the second Phase III clinical study of Myotrophin(R) (rhIGF-1) reached statistical significance on the primary measure and confirmed previous findings that patients with amyotrophic lateral sclerosis (ALS) who received Myotrophin experienced less disease severity and slower progression of disease compared to patients who received placebo. Results of the 183-patient study were presented today at the Sixth International Symposium on ALS/MND in Dublin, Ireland, by Gian Borasio, M.D., a principal investigator for the study and leader of the ALS research group at Ludwig-Maximilians University in Munich, Germany. "We have now confirmed in an international setting with two independent studies of comparable design, that the effects of IGF-1 are clinically important in the treatment of ALS," said Michael Murphy, M.D., Ph.D., Cephalon's senior vice president of worldwide clinical research. "Data from the European study demonstrate statistically significant effects of IGF-1 on disease severity and progression that are consistent with our findings from the North American Phase III study." The European study was conducted at eight medical centers in six countries to evaluate Myotrophin's potential to treat ALS (also known as motor neurone disease (MND), or Lou Gehrig's disease). After an evaluation period of up to three months, eligible patients with ALS were randomized to receive placebo or 0.10 milligrams per kilogram per day of Myotrophin by subcutaneous injection for up to nine months. Patient demographics and disease characteristics were consistent with patients who participated in the North American study. As a group, patients in this study who received Myotrophin showed approximately 22 percent less deterioration than patients receiving placebo, based on their scores on the Appel ALS Rating Scale in analyses of both functional severity of disease and disease progression. Myotrophin also delayed onset of disease-related morbidity as measured by time until a deterioration in respiratory capacity (FVC) or advanced stage of disease (Appel total score greater than or equal to 115). These findings were statistically significant. The Appel ALS Rating Scale is a validated index of disease severity developed in 1982 to provide a quantitative estimate of the clinical condition and disease progression of patients with ALS. It includes assessments of swallowing, speech, respiratory function, muscle strength, and function of upper and lower extremities. Myotrophin was well-tolerated. There were no statistically significant differences between drug and placebo groups for reported adverse events. Earlier this year, Cephalon reported that patients in the North American study who received Myotrophin experienced significantly less disease severity, slower progression of disease, better functional ability and prolonged survival compared to patients who received placebo. These effects were dose-related and statistically significant across all measures. The findings were initially presented on June 10 at a session of the World Federation of Neurology Committee on Motor Neuron Diseases in Talloires, France, and again last week at the 1995 American Neurological Association meeting in Washington, DC. "The successful completion of these two clinical trials is an important milestone towards our goal of delivering innovative therapies to patients suffering from neurodegenerative diseases such as ALS," said Frank Baldino, Jr., Ph.D., Cephalon's President and CEO. "We plan to submit a New Drug Application to the U.S. Food and Drug Administration to market Myotrophin in the United States and are also preparing equivalent regulatory applications in other countries." Cephalon is developing Myotrophin in North America and Europe for use in ALS in collaboration with Chiron and on behalf of Cephalon Clinical Partners, L.P. Cephalon is developing Myotrophin in Japan for use in ALS and other neurological disorders in collaboration with Kyowa Hakko Kogyo Co., Ltd. Cephalon will continue to provide its limited supply of Myotrophin on an open-label basis to all patients who have participated in the North American and European Phase III clinical trials, using drug supplied from its Beltsville, Maryland, manufacturing facility. Cephalon and Chiron are committed to expanding patient access to Myotrophin and are currently awaiting FDA clearance to make Myotrophin available on a limited basis under a treatment investigational new drug program. Chiron Corporation, headquartered in Emeryville, CA, applies biotechnology and other techniques of modern biology and chemistry to develop products intended to improve the quality of life by diagnosing, preventing and treating human disease. Cephalon discovers, develops and markets products to treat neurological disorders. The company's principal focus is on neurological disorders such as ALS, narcolepsy, peripheral neuropathies, Alzheimer's disease, head and spinal injury, and stroke. CONTACT: Jason Rubin or Mary Fisher of Cephalon, 610-344-0200, or Larry Kurtz of Chiron, 510-601-2476/ === end of als 222 ===