=============================================================== == == == ----------- ALS Interest Group ----------- == == ALS Digest (#107, 20 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 .. Mice with human gene to speed ALS research 2 .. ALS in Des Moines 3 .. Communication device for ALS Patients 4 .. Thoughts on swallowing difficulties 5 .. recent ALS citations -- SOD-1 6 .. BIOTEC 94 (1) ===== Mice with human gene to speed ALS research ========== 16-JUN-1994 09:04 MICE WITH HUMAN GENE TO SPEED ALS RESEARCH /ADVANCE/TUCSON, Ariz., June 16 /PRNewswire/ -- The development of mice carrying copies of a human gene will speed the search for treatments of amyotrophic lateral sclerosis (ALS, or Lou Gehrig's disease), the Muscular Dystrophy Association announced today. This is the first time scientists have created an animal version of a human neurodegenerative disease. The advance could lead to more rapid development of potential treatments for some of the 20,000 Americans affected by the fatal neuromuscular disease. Mark Gurney, associate professor of biology at Northwestern University in Chicago, who led the MDA-supported research team, said the use of animal models will allow scientists to test potential ALS treatments for their effectiveness, placing human patients in the most promising clinical trials more quickly. The team published its results in today's issue of Science. Dr. Arnold Gale, a neurologist and MDA's medical information officer, said, Getting an animal model of a disease is a key step in research. A model enables scientists to rapidly test therapies. In this case, it means that those affected by ALS will get therapies sooner that may prolong their lives. The mice were given copies of the human gene carrying a defect known to be a cause of ALS, a disease that paralyzes voluntary muscles and usually results in death within five years. The disorder killed New York Yankees first baseman Lou Gehrig in 1941. The genes were inserted when the mice were at the fertilized egg stage of development. Some mice that took up the defective human genes at this early stage developed ALS after about four months and died after five or six months. (Normal mice of the same type live more than two years.) Those able to breed passed the genetic defect and the disease to their young. A number of biotechnology companies have organized clinical trials in ALS, Gurney said. But it takes time to recruit sufficient numbers of patients into such trials, and the trials last two to three years. If we need 300 mice to test a potential therapy, we can easily breed that many, and since the disease course runs about two months in the mice, we can dramatically accelerate the search for a therapy. Last year, MDA-funded researchers led by Teepu Siddique at Northwestern, also on today's study, and Robert Brown at Boston's Massachusetts General Hospital identified defects in the gene for the enzyme superoxide dismutase 1 (SOD1) as the cause of a small percentage of ALS cases. (While most cases of ALS aren't genetic, the SOD1 finding may be important to all forms of ALS because there's no discernible clinical difference between genetic and non-genetic cases of the disease.) The SOD1 enzyme is thought to detoxify free radicals in the body's cells. Defects in SOD1 seem to cripple its detoxifying capacity, leaving cells, especially nerve cells, vulnerable to damage from free radicals. The defect tested by the Northwestern team caused the SOD1 enzyme to both lose its protective effect and become poisonous to nerve cells. Since 1993, MDA-funded researchers have worked to discover exactly how SOD1 defects cause the death of nerve cells in ALS and devise treatments to halt the process. MDA is a voluntary health agency working to defeat 40 neuromuscular diseases through programs of worldwide research, comprehensive patient and community services and far-reaching professional and public health education. Since the 1950s, the association has spent more than $23 million on ALS research and about $75 million on services to people with the disease. MDA, the world's largest non-governmental sponsor of ALS research and services, supports 240 clinics nationwide, including five centers dedicated to ALS. CONTACT: Jim Brown of MDA public affairs, 602-529-5317 (2) ===== ALS in Des Moines ========== Date : Wed, 15 Jun 94 17:39:09 EDT >From : dlmc@med.unc.edu (David McIlwain) Subject: ALS in Des Moines Mrs. Christine L. Rothlauf wishes to notify anyone interested in ALS clusters that her husband and a co-worker in a company selling janitorial/cleaning supplies have been diagnosed with ALS within 6 months of each other. Anyone interested in this unusual occurence of ALS in 2 employees in a company of 35 total employees should contact Mrs. Christine L. Rotlauf at 4146 11th St., Des Moines, IA 50313, Tel. (515) 282-7731. Lee McIlwain Univ. N. Carolina at Chapel Hill (3) ===== Communication Device for ALS Patients ========== >From : rakesh@cc.gatech.edu (Rakesh Mullick) Subject: Communication Device for ALS Patients Date : Wed, 15 Jun 1994 10:03:52 -0400 (EDT) Here is an article I received from my father who has been involved in a project to develop an inexpensive communication device for ALS patients. Please distribute this ASCII file amongst your group. For additional information please contact: Dr. Satish K. Mullick, Professor, Dept. of Elect. Engg., I. I. T. Kanpur, INDIA - 208016, Email: skm@iitk.ernet.in Phone: 011-91-512-257768 Thanks, Rakesh Mullick A Communication Aid for ALS Handicapped Commonly known as Lou Gehrig's or motor neuron disease, amytrophic lateral sclerosis (ALS) is at present an incurable rare disease in which the nerves that control motor muscular activity degenerate. As a result, the patient gradually loses control over all voluntary muscle movements including speech. Ultimately the breathing and swallowing muscles are also affected leading to death. Stephen Hawking, one of the greatest theoretical physicists of our time and author of the bestseller ``A Brief History of Time'' is a rare survivor of ALS for 20 years. Most sufferers are not so lucky and succumb to disease's onslaught in two to four years. Since their sensory inputs and brain are not affected, these patients have intense desire to communicate, not merely for the purpose of getting attended to their physical needs, but also to convey their feelings and emotions. It has been observed that these patients retain the ability to move their eyeballs and to blink. The Eyegazer System developed by IC Technologies in U.S.A. enables the patient to stare at control keys displayed on a computer screen to perform functions including speech synthesis, typing, using a telephone and controlling environmental surroundings. However it is quite expensive with a price-tag of 25,000. An inexpensive system, utilizing the voluntary eye blinking ability, has been developed at I.I.T. Kanpur by two undergraduate students Navin Khaneja and Ashish Mathur as their final year project under the guidance of Prof. S.K. Mullick of the Dept. of Electrical Engineering. The motivation for the work came from a personal tragedy whereby Prof. Mullick lost his sister last year of this disease. She left behind a very poignant and touching four page letter, painstakingly compiled by her daughter letter-by-letter, with the help of an alphabet chart, over a period of many days. The system detects the voluntary eye blink signal using a low power LED and a pair of phototransistors mounted on the spectacles that the patient is made to wear. The detected signal interfaced to a PC is made to stop for a short duration, a moving cursor on the chosen alphabet or other communication symbols displayed on a computer monitor. The chosen symbol is immediately displayed in a window on the screen and text can thus be composed letter by letter. Besides, there is a menu having `Display', `Print', `Edit' and `Exit' options. The inputted text may be converted to speech using the inbuilt facility of some PC's, or using a commercially available text to speech card. Admittedly, for this application, the system is slow taking about 2 -- 3 hours to compose a page of text, but very inexpensive compared to the Eyegazer System, the cost being essentially of the PC used in the system. For drawing attention of an attendant at home or the paramedical staff in a hospital, to attend to the personal physical needs, the patient can move the cursor to the displayed icons symbolizing these needs and at the same time vocalizing with the help of prerecorded messages associated with these icons. ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ |RAKESH MULLICK, (PhD Student,EE Dept) |Email: rakesh@cc.gatech.edu | |Medical Informatics Lab., GVU Center, CoC,| gt3172a@acme.gatech.edu | |Georgia Institute of Technology, |UUCP: ...!gatech!cc!rakesh | |Atlanta, GA, 30332-0280 |Fax: (404)-853-0673 | | |Phone: 894-9761(Off),9635(Lab) | |Res: 5664 Seville Ln., Stone Mtn, GA 30087| (404)-564-0296 (Res.) | ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ (4) ===== Thoughts on swallowing difficulties ========== Date : Wed, 08 Jun 94 11:30:49 EST >From : "Mike Doliton" Subject: Thoughts on swallowing difficulties Thoughts on swallowing difficulties: As the ALS progresses speech declines and swallowing starts to become a problem. The reason why swallowing becomes difficult is that the swallowing muscles get weak and the swallow doesn't complete. To swallow properly always have a glass of water handy to wash down food that gets stuck. A pocket forms at the epiglottis. Usually the epiglottis backs all the way against to throat wall. But when it gets weak it forms a pocket between itself and the throat wall. Whey you swallow sometimes food gets caught in this pocket and causes a choking sensation because it pushes the epiglottis over the windpipe. Coughing doesn't clear this condition because the food isn't going down the windpipe. This causes a very strange reaction. Mucous starts forming and further complicates things by covering the epiglottis and causing air to be blocked from the windpipe. The thing to do is to swallow water to clear the pocket of the food. But be very careful not to get the water down the windpipe. Swallow very deliberately and concentrate on what you are doing. Sometimes when we are breathing and swallowing saliva the saliva gets into this packet. This causes an irritating burning sensation in the throat. Again drink some water to clear the pocket out. Sometimes when drinking water or other thin liquids some of the liquid goes down the windpipe. This is where the coughing helps. With the vocal cords relaxed they are almost shut so when you try to cough you can't without making a loud choking sound. I have found that at the end of the exhale the cords separate enough to get some air out and clear the windpipe of the liquid. If you can sneeze the vocal cords are forced to open by the action of the sneeze. I think the muscles supporting the cords actually cause the cords to open up during a sneeze. It may help to have some pepper around for this. Of course as the muscles get weaker and weaker as the ALS progresses it may not be possible to do the thinks I mentioned above. Then a suction machine becomes necessary to clear the throat. By that time the ALS person should also have a feeding tube in place to prevent food and liquids from getting into the windpipe. As the speech starts getting difficult it helps to open the mouth wide and exaggerate the sounds. Talk very deliberately and slowly to attack each syllable. If a thought is impossible to say, try saying it a different way with mono syllabic words. Make you lip movements pronounced so that people that can read lips can read your lips. Also speaking in a lower volume where its quiet helps because the throat muscles can form the sounds when the air flowing through your mouth is moving with less force. It also helps to have people around know the Heimlick Menuver in case things get out of control. But make these people aware that you usually can clear your throat yourself. I have a 100% record of clearing my throat myself. Use hand signals. For example a thumb up means your handling it yourself. A thumb down means you need the Heimlick. It also helps to have a bottle of water at your side constantly even when you sleep. And have a suction pump available too. (5) ===== recent ALS citations -- SOD-1 ========== =============================================== Title : Genetic linkage analysis of familial amyotrophic : lateral sclerosis using human chromosome 21 micro- : satellite DNA markers Author : Rosen D.R.; Sapp P.; O'Regan J.; McKenna-Yasek D.; : Schlumpf K.S.; Haines J.L.; Gusella J.F.; Horvitz H.R.; : Brown R.H. Jr.; Source : 1994 51/1 (61-69) American Journal of Medical Genetics Abstract : Amyotrophic lateral sclerosis (ALS; Lou Gehrig's Disease) is a lethal neurodegenerative disease of upper and lower motorneurons in the brain and spinal cord. We previously reported linkage of a gene for familial ALS (FALS) to human chromosome 21 using 4 restriction fragment length polymorphism DNA markers [Siddique et al.: N Engl J Med 324:1381-1384, 1991] and identified disease-associated mutations in the superoxide dismutase (SOD)-1 gene in some ALS families [Rosen et al.: Nature 362:59-62, 1993]. We report here the genetic linkage data that led us to examine the SOD-1 gene for mutations. We also report a new micro- satellite DNA marker for D21S63, derived from the cosmid PW517 [VanKeuren et al.: Am J Hum Genet 38:793-804, 1986]. Ten microsatellite DNA markers, including the new marker D21S63, were used to reinvestigate linkage of FALS to chromosome 21. Genetic linkage analysis performed with 13 ALS families for these 10 DNA markers confirmed the presence of a FALS gene on chromosome 21. The highest total 2-point LOD score for all families was 4.33, obtained at a distance of 10 cM from the marker D21S223. For 5 ALS families linked to chromosome 21, a peak 2-point LOD score of 5.94 was obtained at the DNA marker D21S223. A multipoint score of 6.50 was obtained with the markers D21S213, D21S223, D21S167, and FALS for 5 chromosome 21-linked ALS families. The haplotypes of these families for the 10 DNA markers revealed recombination events that further refined the location of the FALS gene to a segment of approximately 5 megabases (Mb) between D21S213 and D21S219. The only characterized gene within this segment was SOD-1, the structural gene for Cu, Zn SOD. =============================================== Title : Chronic inhibition of superoxide dismutase produces : apoptotic death of spinal neurons Author : Rothstein J.D.; Bristol L.A.; Hosler B.; Brown R.H. Jr.; : Kuncl R.W.; Source : 1994 91/10 (4155-4159) Proceedings of the National : Academy of Sciences of the United States of America Abstract : Mutations in the gene for Cu/Zn superoxide dismutase (SOD1) have been detected in some families with an autosomal dominant form of amyotrophic lateral sclerosis; these mutations appear to reduce the activity of this enzyme. To determine whether decreased SOD activity could contribute to motor neuron loss, SOD1 was inhibited chronically with either antisense oligodeoxynucleotides or diethyldithiocarbamate in spinal cord organotypic cultures. Chronic inhibition of SOD resulted in the apoptotic degeneration of spinal neurons, including motor neurons, over several weeks. Motor neuron loss was markedly potentiated by the inhibition of glutamate transport. In this paradigm, motor neuron toxicity could be entirely prevented by the antioxidant N-acetylcysteine and, to a lesser extent, by the non-N-methyl-D- aspartate glutamate receptor antagonist 1-(4-aminophenyl)-4-methyl-7,8- methylenedioxy-5H-2,3-benzodiazepine hydrochloride. These data support the hypothesis that the loss of motor neurons in familial amyotrophic lateral sclerosis could be due to a reduction in SOD1 activity, possibly potentiated by inefficient glutamate transport. (6) ===== BIOTEC 94 ========== BIOTEC 94 Forum of Biotechnology/Biomedicine for Science, Technology and Medicine Duesseldorf, Germany - November 16-19, 1994 **************************************************************** In co-operation with the Institute of Microbiology of the Heinrich- Heine-Universitaet Duesseldorf (Germany) and the Messe Duesseldorf we organize the BIOTEC 94 Forum of Biotechnology, which takes place parallel with the MEDICA Fair, one of the world's largest fairs in the field of medicine. The International Forum of Biotechnology BIOTEC 94 offers you an ideal platform for presenting your state-of-the-art innovations in the field of research and development in industry and higher education. In addition to the scientific BIOTEC Congress we give you the opportunity to present your products, services and developments within the framework of the BIOTEC Special Exhibition. Thanks to its links with the MEDICA and an expected number of about 100,000 visitors, the BIOTEC Special Exhibition promises to generate widespread interest. Additionally you can take part in the Technology Forum, which opens the way to communication with scientists, practitioners, politicians and the industry. Andreas Bohlen Department of Research and Technology Transfer University of Duesseldorf ************************************************************** * Heinrich-Heine-Universitaet Duesseldorf * * Forschungs- und Technologie-Transfer * * Dr. Andreas Bohlen * * Universitaetsstr. 1 * * Gebaeude 16.11 * * D-40225 Duesseldorf * * * * Tel. (0211) 3 11-23 09 * * Fax (0211) 34 22 29 * * E-Mail hempel@uni-duesseldorf.de * ************************************************************** * * * Universitaet Potsdam * * Potsdamer Informations- und Technologie-Transfer (PITT) * * Dr. Andreas Bohlen * * Am Neuen Palais 10 * * D-14469 Potsdam * * * * Tel./Fax (0331) 9 77-11 19 * * E-Mail bohlen@hp.rz.uni-potsdam.de * ************************************************************** == end of als 107 ==