Date: Sun, 18 Jun 95 21:13:39 -0400 From: Bob Broedel To: als@huey.met.fsu.edu Subject: ALSD199 ALS-ON-LINE =============================================================== == == == ----------- ALS Interest Group ----------- == == ALS Digest (#199, 18 June 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 == == 750+ 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 .. OHSU e-mail list request 2 .. 5th Annual Lou Gehrig's Day 3 .. IGF-1 alternative treatment? 4 .. NIH budget cuts, "living wills" & other matters 5 .. Myotrophin enquiry (from Australia) 6 .. Myotrophin 7 .. Motor Neurone Drug Success 8 .. MDA Research Report #57 (1) ===== OHSU e-mail list request ========== Date : Tue, 13 Jun 1995 17:52:23 -0700 (PDT) >From : Leigh Redding Subject: OHSU e-mail list request Our local Neurological Clinic has asked if we had the e-mail addresses of those online that use their clinic at OHSU. I do not. I was wondering if you would be so kind as to broadcast a request for those that are online so that they would e-mail us and we would compile the list for the clinic. I'm not being presumptuous but something like the following should catch their eye, whatever works. Thanks, Leigh W H O ALS patients on-line ALS Caregivers on-line W H E R E OHSU - Oregon Health Sciences University - Serving Oregon, Southern Washington and Southwestern Idaho W H A T Dr. Johnston of OHSU's ALS Clinic has asked if we can compile a list of their Patients and Caregivers that are on-line. Send e-mail To: Leigh Redding Subject: OHSU ALS on-line In the give your name and say if you are you a Patient like me or a Caregiver, OK? Thanks, and I will get this stuff to Dr. Johnston. Leigh (2) ===== 5th Annual Lou Gehrig's Day ========== >From : vitale@dectlk.enet.dec.com Date : Wed, 14 Jun 95 20:18:14 EDT Subject: pls publish this in the next ALS on-line. Tx.\tony The Massachusetts Chapter of the ALS Association is sponsoring its 5th Annual Lou Gehrig's Day at Fenway Park on Sunday, July 23, 1995. A $40 donation includes a ticket to the game (the Red Sox vs. the Minnesota Twins) as well as a special catered ballpark lunch at Fenway Park's Diamond Room beginning at 11:30 a.m. until gametime at p.m. Highlights during lunch include appearances by Red Sox players who will be on hand to sign autographs. A raffle of exciting prizes will also be held, including a baseball autographed by the entire Red Sox team. Handicap accessibility and seating are available. To reserve your tickets, you can either call the Massachusetts Chapter office at (617) 245-2133 or send your check directly to 7 Lincoln Street, Wakefield, Mass. 01880. Checks should be made payable to the ALS Association, Mass. Chapter. Tickets are $40 each. Please support this important fundraiser, which is a great way to spend a summer afternoon. All proceeds will be used for patient support and services and public education. Please help us help those who are living with Lou Gehrig's Disease. (3) ===== IGF-1 alternative treatment? ========== Date : Fri, 16 Jun 1995 18:06:46 EDT >From : SYKB36A@prodigy.com (MR GERARD LAURENZANO) Subject: IGF-1 alternative treatment? As we wait for IGF-1 approval the following might be worth pursuing. This statement (by Sandy Shaw and Doug Pearson) is excerpted from "AGE News" p.5, April 1995. " ...We know two physicians who have done studies in small groups of patients with arginine-choline-B-5 supplements. In these studies (one was open, the other was double-blind, placebo controlled), women were given a dose of 12 grams of arginine, while men received 18 grams of arginine, in combination with choline (1 g per each 6 g of arginine) and vitamin B-5 (2/3 g of B-5 per each 6 g of arginine). Most subjects had at least DOUBLED IGF-1 levels." Paragraph omitted. "We would like to add arginine stimulates pituitary release of growth hormone via a cholinergic mechanism..." Gerry from NJ (4) ===== NIH budget cuts, "living wills" & other matters ========== Date : Sat, 10 Jun 1995 09:58:52 -0700 >From : jh@islandnet.com (John Hofsess) Subject: NIH budget cuts, "living wills" & other matters ITEM ONE: Concerning the forwarded article about threatened cuts in the National Institute of Health budget, your readers may appreciate knowing that in addition to the telephone and fax lines listed in that article for various Senators and Representatives, they can obtain email addresses for many U.S. government officials and departments through DeathNET (http://www.islandnet.com/~deathnet) under the category of ERGO! Online Library. The files may be downloaded for future reference - although one should be aware that we update them regularly. Many readers of "ALS Digest" may find it easier to compose and send email than to send faxes. ITEM TWO: A couple of readers of "ALS Digest" sent email messages to me asking if we have articles on hand that we could post to the digest, particularly articles on "living wills." At present, do we do not...but we are working on establishing a Living Will Center on DeathNET (possibly operational in about one month's time) which will provide specifics, state by state (and province by province in Canada) on "living will" legislation in each jurisdiction, and also provide valid documents for each area. In the meantime however anyone who sends us email (rights@islandnet.com) asking for "living will" information and including a *postal* address, will be sent an InfoPAK with such information as we have available in printed form - free of charge anywhere in the world. ITEM THREE: We have two members of the Right to Die Society of Canada who have asked us to help find out if voice-activated computer equipment is available for those who still can speak but have little or no mobility in arms and hands. We are aware that voice-activated computers do exist but the real issue is cost and availability. In particular, these individuals are asking us if there are any organizations (ALS Societies, or other) who help to provide this equipment to those for whom communication is of vital importance. We would welcome hearing of the use of such equipment from any quarter... but most particlarly about the availability of such equipment in Ontario and British Columbia. John Hofsess executive director the right to die society of canada (5) ===== Myotrophin enquiry (from Australia) ========== >From : "paulf" Date : Fri, 16 Jun 1995 10:39:49 -0500 Subject: Myotrophin enquiry (from Australia) I have just read the news on myotrophin stage III trials and am interested in contacting Cephalon Inc., so I would appreciate it if anyone could pass on to me their e-mail address or FAX number. Thanks in advance, Paul Failla. (6) ===== Myotrophin ========== HEALTH NEWS DAILY Tuesday June 13, 1995 Cephalon/Chiron's Myotrophin (IGF-1) effective in Lou Gehrig's disease, company reports at neurology meeting in France. CEPHALON/CHIRON's MYOTROPHIN SHOWS 25% REDUCTION IN DISEASE PROGRESSION in patients with amytrophic lateral sclerosis compared to those receiving placebo, according to results of a Phase III study presented June 10 by Cephalon Senior-VP Michael Murphy, MD/PhD, at the World Federation of Neurology Committee on Motor Neuron Diseases in Talloires, France. Patients receiving the recombinant insulin-like growth factor showed significantly less deterioration than placebo on the Appel ALS Rating Scale in the areas of rate of change and functional severity of disease. < many parts deleted > While the nine-month study did not have enough deaths to allow assessment of survival, the company estimates from data out to 14 months that there is a four-month difference in survival between Myotrophin-treated and placebo- treated patients. Data from a 959-patient study of Rhone-Poulenc Rorer's Rilutek (riluzole) in ALS presented recently at the American Academy of Neurology annual meeting showed a survival advantage for riluzole over placebo at 12 months, but the difference began to lose statistical significance at 18 months. RPR filed for a Treatment IND for Rilutek on May 22. < parts deleted > Cephalon is continuing to provide Myotrophin to over 300 patients who participated in the clinical trials. The company is producing limited quantities of Myotrophin at its Beltsville, Maryland facility until Chiron completes a larger plant at its Vacaville, California site. (7) ===== Motor Neurone Drug Success ========== FINANCIAL TIMES Tuesday June 13, 1995 MOTOR NEURONE DRUG SUCCESS By CLIVE COOKSON, Science Editor The most encouraging results obtained so far for any treatment of a degenerative nerve disease were announced yesterday by Cephalon, a US biotechnology company. < parts deleted > 'The results of this study are dramatic and clearly herald a change in the way we treat this devastating disease,' said Dr Dale Lange, co-director of ALS treatment at New York's Columbia-Presbyterian Medical Centre. 'For the first time, we have an agent with a strong basic science rationale verified by a clinical trial.' In the nine-month study, undertaken at eight hospitals in the US and Canada, patients who received Myotrophin injections showed 25 per cent less deterioration than those who received placebo (dummy) injections. They were therefore able to maintain an independent lifestyle for several months longer. < parts deleted > Famous sufferers include Lou Gehrig (baseball star), David Niven (actor) and Don Revie (football manager). Patients typically die within two to five years. Prof Stephen Hawking, the Cambridge University cosmologist, has an exceptionally stable form of ALS. < parts deleted > IGF-1 cannot stop the underlying disease process or cure ALS (whose ultimate cause is unknown). But the Cephalon results suggest it may enable the motor neurones to keep functioning for a few extra months or even years. (8) ===== MDA Research Report #57 ========== Date : 12 Jun 95 23:01:24 EDT >From : Barry Goldberg <71154.330@compuserve.com> Subject: MDA Research Report #57 Here's the latest research report from MDA which was distributed to all field offices and clinic directors. I hope you find some of the information useful. Research Update from the Muscular Dystrophy Association (MDA) MDA STAFF RESEARCH UPDATE -- SRU #57 -- 06/07/95 ************************************************ The accumulation of neurofilaments within a certain part of a neuron called the AXON has been suggested as a possible cause of some forms of AMYOTROPHIC LATERAL SCLEROSIS (ALS). Two findings that led to this theory include the observation that mice overexpressing neurofilaments experience motor neuron destruction and that one of the neurofilament genes, NF-H, in some people affected by ALS may contain a defect. Researchers recently studied what the actual effects might be of having too many neurofilaments in axons of neurons. They concluded that the transport of components necessary for the maintenance of the axon is disrupted when neurofilaments accumulate. This leads to the degeneration of the axon and may cause motor-neuron death but further research is necessary in order to fully understand how excessive quantities of neurofilaments may be involved in ALS. (Collard, J-F. et al. Nature 375:61-64, 1995). Scientists have proposed that defects on chromosome 22 may affect not only the NF-H gene but other genes in the area as well, and these defects may be associated with some forms of ALS. There is some circumstantial evidence to support this theory, however, additional genetic data is required to reach conclusions regarding what genes may be defective and how the altered gene products might cause the disease. Researchers are optimistic about understanding in the not-too-distant future how ALS may develop from altered neurofilament functions, altered free-radical activity, altered excitotoxin activity and autoimmune problems, as well as how nerve growth factors may be involved. (Meyer, M.A. and Potter, N.T. Muscle and Nerve 1995; 18:536-539 and Al-Chalabi, A. et al. Muscle and Nerve 1995; 18:540-545). A form of SPINAL MUSCULAR ATROPHY (SMA) called DISTAL SMA can clinically resemble type II Charcot-Marie-Tooth disease. Weakness in distal SMA is primarily seen in the leg and foot muscles and later may appear in the hands and arms. Dominant and recessive types of inheritance have been found as well as sporadic cases. Researchers describe a family affected by autosomal dominant distal SMA in which genetic analysis shows that the disorder is not associated with defects on chromosome 5 as is the case with SMA types I, II and III. (Boylan, K.B. et al. Neurology 1995; 45:699-704). Genetic researchers are refining the location on chromosome 8q of the gene defect for ATAXIA with vitamin E deficiency (AVED). A number of families affected by AVED have been identified, and indications are that the Friedreich's ataxia-like disorder is associated with populations of Northern African descent. A strong candidate for involvement in AVED is the vitamin E transfer protein in liver since biochemical studies showed abnormal processing of the vitamin in that organ. Clinical researchers suggest that early detection of the disorder, before onset of progressive neurodegeneration, can allow for treatment to stabilize the condition or prevent loss of neurological function. (Doerflinger, N. et al. American Journal of Human Genetics 1995; 56:1116-1124). MYOTUBULAR MYOPATHY (MTM1) is generally considered more severe than other types of congenital myopathies and is known to be associated with a defect on the X chromosome. A study of an individual affected by an unrelated disorder, who has an unusually large deletion in the area of the MTM1 gene on the X chromosome, has enabled researchers to substantially reduce the size of the region in which they expect to find the defective gene for MTM1. A similar gene mapping discovery in the past -- involving a defect in the dystrophin gene associated with Duchenne muscular dystrophy -- enhanced tremendously progress in disease gene identification. (Dahl, N. et al. American Journal of Human Genetics 1995; 56:1108-1115). MYOTONIC MUSCULAR DYSTROPHY (DM) is associated with a defect located within a gene for a protein called myotonic dystrophy protein kinase (DMPK), also called human myotonin protein KINASE (HMPK). HMPK was previously unknown, however, scientists already have found that the protein is present throughout the body and they are now working to define its functions. Altered sodium channel activity may be involved with one abnormality in DM -- myotonia. Therefore, researchers looked to see if HMPK interacts with the sodium channel. The results demonstrated that HMPK can modify the sodium channel to affect the channel's function and that this is most likely an aspect of HMPK's role. Interestingly, HMPK from individuals affected by DM and HMPK from those unaffected by the disease were found to behave similarly in their effects on the sodium channel. This result was not unexpected as the defect in the HMPK gene is located in an area that would more likely affect the amount of protein produced not the quality of the protein produced. (Mounsey, J.P. et al. Journal of Clinical Investigation 1995; 95:2379-2384). The MYOTONIC DYSTROPHY (DM) gene defect is an expanded, unstable region in the myotonic dystrophy protein kinase gene. The larger the expanded area is the more severe the disorder. How this expanded gene area affects the protein kinase gene or other nearby genes is not fully understood. Researchers have been working to determine if the defect causes some type of alteration in the function of the protein kinase or whether the defect might be altering the gene's coded message that is used to produce the protein. Recent evidence has shown that in individuals with myotonic dystrophy there may be a problem in the processing of the message from the protein kinase gene. The result is a dramatically reduced amount of the protein kinase message that would be available for the production of the protein. Additional experiments need to be performed to verify these findings; however, if they prove to be correct, myotonic dystrophy would be the first known human disease to arise by such a mechanism. (Wang, J. et al. Human Molecular Genetics 1995; 4:599-606). In general, the unstable repeat defect in the MYOTONIC DYSTROPHY GENE (DMPK) varies in size and the severity of the disorder increases accordingly. Smaller repeats are associated with mild symptoms such as cataracts while moderately sized repeats also involve signs of dystrophy, myotonia and effects in a number of different organs. The largest repeats can result in more serious effects such as mental impairment, endocrine defects and sterility. Right next to the DMPK gene is a gene called DMR-N9 (or in humans the 59 gene), and researchers have suspected that the unstable repeat defect in DMPK could affect the neighboring gene. By studying the DMR-N9 protein, scientists have determined that the protein is expressed at a low level throughout the body and at a higher level in brain and testis. These results led the researchers to conclude that DMR-N9 is a candidate gene for also being involved in DM. (Jansen, G. et al. Human Molecular Genetics 1995; 4:843-852). PROXIMAL MYOTONIC MYOPATHY (PROMM) is a newly described disorder with similarities to myotonic dystrophy (DM). Clinical features of PROMM that are also features of DM include myotonia, cataracts, muscle weakness and cardiac abnormalities. Other characteristics of DM such as facial weakness, mental disturbances and significant muscular atrophy are not experienced by individuals with PROMM. Genetic studies demonstrate that the DM gene defect is not present in PROMM families. More work is necessary in order to define the genetic defect associated with PROMM, however, it is important to distinguish between the two disorders since individuals with PROMM have a more favorable disease course. (Letter to the Editor Moxley, R.T. and Ricker, K. Muscle and Nerve 1995; 18:557). LAMBERT-EATON SYNDROME (LES) is a disorder involving an autoimmune response that impairs the transmission of signals at the junction between nerve and muscle. A certain type of calcium channel assists in the process of signal transmission from the nerve ending, however, these calcium channels are attacked by autoantibodies that are mistakenly produced in individuals with LES resulting in impaired signaling at the neuromuscular junction. LES is often associated with the presence of small-cell lung carcinoma and it appears that the autoimmune response creates autoantibodies to calcium channels in the tumor. One particular type of calcium channel autoantibody (anti-P/Q) was found in small-cell lung carcinomas and tests demonstrated that 95% of the LES individuals, with or without tumors, were positive for anti-P/Q as well. (Lennon, V.A. et al. New England Journal of Medicine 1995; 332:1467-1474). If an inherited disorder in animals resembles a human genetic disease, the animal can serve as a model of the human disorder helping to identify the defective gene involved, and the model may eventually be useful in the design of a treatment. The myd mouse has features similar to FACIOSCAPULOHUMERAL MUSCULAR DYSTROPHY (FSH) and researchers are working to locate and identify the defective gene associated with the disease in mice. The myd gene was found to be on mouse chromosome 8 in an area that appears to be comparable to human chromosome 4 in the region of the FSH gene. The work can enhance the progress toward identifying the FSH gene in people. (Mathews, K.D. et al. Muscle and Nerve 1995; Suppl 2:S98-S102). There is a wide range in the age of onset for FACIOSCAPULOHUMERAL MUSCULAR DYSTROPHY (FSH), and scientists have been looking for a connection between the molecular genetic features of the FSH gene area and the age of onset. Generally a young age of onset is associated with the more severe cases of FSH, and even though the gene defect has not been identified as yet, geneticists would like to be able to find an association between the severity of the disorder and the features of the FSH gene region. Researchers found that the size of a deletion in a portion of the FSH gene area correlated with the severity of FSH observed. This finding along with the fact that variability of FSH can be seen in successive generations within a family could explain the variation in the expression of the disorder. (Lunt, P. et al. Human Molecular Genetics 1995; 4:951-958 and Muscle and Nerve 1995; Suppl 2:S103-S109). --- MDA -- Working to find the cure for neuromuscular disease --- === end of als 199 ===