Date: Mon, 31 Oct 94 23:03:46 -0500 From: Bob Broedel To: als@huey.met.fsu.edu Subject: ALSD#140 ALS-ON-LINE =============================================================== == == == ----------- ALS Interest Group ----------- == == ALS Digest (#140, 31 October 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. The ALS Digest is == == published (approximately) weekly. Currently there are == == 380+ 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 .. HELP! 2 .. ALS & immunology 3 .. ALS/riluzole interim results 4 .. longevity 5 .. Death 6 .. references 7 .. American Neurological Association Meetings - Industry Report (1) ===== HELP! ========== >From : grassc@ohsu.edu (Carol Grass,PC,SoN-Student) Date : Mon Oct 31 12:36:18 PST 1994 Subject: HELP! I am an RN working with ALS patients in a clinical setting. I have a client who has copious thick saliva and is unable to use his arms or hands. He is set up at work to use his computor to work and communicate, but the saliva is becoming an overwhelming problem. We have tried Transderm, Amitryptiline in various doses and times as well as papyra for thick tenacious "stuff". Any ideas? This may be the problem that forces him to be home with a caregiver in his early fifties after so valiantly fighting the obstacles that ALS has brought. Any ideas short of a caregiver at work to wipe his chin and suction? I do not have access to prodigy so, any input from there would be welcome. Thanks (2) ===== ALS & immunology ========== Date : Thu, 27 Oct 1994 03:27:03 -0400 >From : Millec@aol.com Subject: ALS Digest I am writing on behalf of Robert who is a man in his ealy fourties who has ALS, is on a vent and right now lives in a nursing home. He still has speech and movement of his head and neck but he cannot use his computer so I am writing for him. He wants to know any available information on immunology as relates to the study of ALS. He would like to know who is doing such studies and what their direction is. If there are any replies to these questions, I will print them and take them to him. Thanks, Annie (3) ===== ALS/riluzole interim results ========== Date : Wed, 26 Oct 94 12:34:44 EST >From : "Mike Doliton" Subject: ALS/riluzole interim results To All: I received a communications from Rhone-Poulenc Rorer the people who make Riluzole. I was expecting some interim results. A synopsis follows: "The Steering Committee said a) it is not possible to determine efficacy at this time b) the study should continue. RPR plans to conduct a final analysis utilizing data with a cut-off date of December 31, 1994". Regards, Michael Doliton, Sony Medical Systems (4) ===== longevity ========== Date : Tue, 25 Oct 1994 22:22:32 -0400 >From : LIPIDS@aol.com Subject: longevity THE MDA IN ROANOKE,VA TOLD ME OF A GENTLEMAN THAT LIVED 45 YEARS WITH ALS. THE MAJORITY OF THE TIME THE GRIP IN HIS ONE HAND WAS THE ONLY SYMPTOM. (5) ===== Death ========== >From : Tom Havey Subject: Death Date : Mon, 31 Oct 94 9:24:34 MST My grandmother, 88 yrs.old, diagnosed with ALS 3 months ago, died this past weekend. Her muscles had pretty much quit working by Friday, she couldn't talk, eat; she just lay there waiting... this seems to be a pretty quick duration of ALS. She took no medication, no oxygen. She was ready to go. She wanted to go. All is well...now. Any and all comments are greatly welcome. Tom Havey (6) ===== references ========== =============================================== Title : Reversible cognitive decline during high-dose alpha- : interferon treatment. Author : Poutiainen E; Hokkanen L; Niemi ML; Farkkila M Source : Pharmacology, Biochemistry and Behavior : 1994 Apr;47(4):901-5 Abstract : The cognitive effects of high-dose human leukocyte alpha-interferon (IFN- alpha) treatment were evaluated among 15 patients with the newly diagnosed spinal form of amyotrophic lateral sclerosis (ALS). To confirm the earlier findings showing reversible effects on cognitive performance and to exclude confounding effects, a randomized blinded placebo controlled study was conducted. Twelve patients with continuous intravenous IFN-alpha-infusion treatment over five days and 3 placebo control patients were neuropsycho- logically evaluated. The neuropsychological examination included tests of intelligence, memory, complex mental processing, visuoconstructional skills, writing, and calculation. A clear difference in the performance profiles of the placebo and the IFN-alpha-treated patient groups was detected: The IFN-alpha group showed significant deterioration during treatment in the digit span backwards task, logical verbal memory task, calculation ability, and writing time, while improvement was seen after treatment. Concomitant fever did not explain the findings. In the placebo group an improvement indicating a learning effect in the three consecutive measurements was found. The reversible cognitive deterioration indicates a clear CNS effect during the IFN-alpha treatment. =============================================== Title : Genetic linkage analysis of familial amyotrophic lateral : sclerosis using human chromosome 21 microsatellite DNA : markers. Author : Rosen DR; Sapp P; O'Regan J; McKenna-Yasek D; Schlumpf KS; : Haines JL; Gusella JF; Horvitz HR; Brown RH Jr Source : American Journal of Medical Genetics : 1994 May 15;51(1):61-9 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 microsatellite 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.(ABSTRACT TRUNCATED AT 250 WORDS) =============================================== Title : Dental management of long-term amyotrophic lateral : sclerosis: case report. Author : Asher RS; Alfred T Source : Special Care in Dentistry 1993 Nov;13(6):241-4 Abstract : Amyotrophic lateral sclerosis (ALS) is a progressive motor neuron disease. Methods of dental treatment of a young male patient with ALS are presented. This case is unusual in several respects: the early age of onset, the long survival time, and the period of time in which the case was followed in our dental clinic. Aspects of ALS which are of concern to dentistry, as related to clinical care and strategies for effective oral health delivery, are presented. =============================================== Title : Sympathetic skin response abnormalities in amyotrophic : lateral sclerosis [letter] Author : Masur H; Schulte-Oversohl U; Oberwittler C Source : Muscle and Nerve 1994 Aug;17(8):957-8 =============================================== Title : A mathematical model of pathogenesis in idiopathic : parkinsonism. Author : Schulzer M; Lee CS; Mak EK; Vingerhoets FJ; Calne DB Source : Brain 1994 Jun;117 ( Pt 3)( ):509-16 Abstract : We used our observations relating clinical deficits in idiopathic parkinsonism (IP) to age and to disease duration (Lee et al, Brain 1994; 117: 501-7), to develop a mathematical model of the temporal profile of neurodegeneration in IP. We also examined other sets of relevant published observations and applied three additional assumptions which permitted the formulation of this model. Our model indicates that accelerating or decelerating processes should be excluded as the driving forces behind neuronal death in IP. Mechanisms in accord with the model include: (i) an event that kills some neurons and damages others in such a way that their life expectation is reduced; or (ii) an event that starts a process which is continuously killing healthy neurons at a constant rate. The model enables us to extrapolate back to estimate when the causal event occurred. It also explains why IP proceeds more rapidly in older patients. The model has potential relevance to other neurodegenerative disorders, such as Alzheimer's disease and amyotrophic lateral sclerosis. =============================================== Title : Expression of chromogranin A in lesions in the central : nervous system from patients with neurological diseases. Author : Yasuhara O; Kawamata T; Aimi Y; McGeer EG; McGeer PL Source : Neuroscience Letters 1994 Mar 28;170(1):13-6 Abstract : Expression of chromogranin A in various neurological diseases was examined immunohistochemically using purified anti-human chromogranin A antiserum. The antibody stained dystrophic neurites in senile plaques in Alzheimer disease brain, Pick bodies and ballooned neurons in Pick's disease brain, some Lewy bodies in the substantia nigra of Parkinson's disease, and axonal swellings in various neurological conditions including Parkinson's disease, striatonigral degeneration, Shy-Drager syndrome, amyotrophic lateral sclerosis and cerebral infarction. The present study shows that expression of chromogranin A is not an exclusive feature of Alzheimer disease or Pick's disease, and indicates that it could be a useful marker for various neurological diseases. =============================================== Title : Transport of cycasin by the intestinal Na+/glucose : cotransporter. Author : Hirayama B; Hazama A; Loo DF; Wright EM; Kisby GE Source : Biochimica et Biophysica Acta 1994 Jul 13;1193(1):151-4 Abstract : The medicinal and food use of seed from the cycad plant (Cycas spp.), which contains the neurotoxin cycasin, is a proposed etiological factor for amyotrophic lateral sclerosis/Parkinsonism dementia complex (ALS/PDC), a prototypical neurodegenerative disease found in the western Pacific. Cycasin, the beta-D-glucoside of methylazoxymethanol might enter neurons and other cells via a glucose transporter. Since the intestinal brush- border Na+/glucose cotransporter plays a major role in the absorption of monosaccharides, the following studies were conducted to determine if cycasin, the beta-D-glucoside of methylazoxymethanol, is a substrate for the transporter. We measured the ability of cycasin to (i) inhibit Na+/ glucose uptake into rabbit intestinal brush-border membrane vesicles, and (ii) to generate current by the cloned Na+/glucose cotransporter (SGLT1) expressed in Xenopus laevis oocytes. The results show that cycasin inhibits Na(+)-dependent sugar transport in the vesicles, and cycasin generates phlorizin-sensitive currents in oocytes. We conclude that cycasin is a substrate for the intestinal brush-border Na+/glucose cotransporter, albeit with a lower affinity than D-glucose. This suggests that cycasin may be absorbed from the gut lumen by the cotransporter, and as a result either cycasin or the aglycone is presented to the blood- brain barrier for uptake into the brain. =============================================== (7) ===== American Neurological Association Meetings - Industry Report ========== American Neurological Association Meetings - Industry Report PAINWEBBER INC.: Miller, L.I. 09-15-94 Health Care Group American Neurological Association Annual Meetings Any brainy ideas? Highlights < most of this 6 page document has been deleted > * Research reports and preclinical studies will likely illustrate the potential for SOD as a treatment for ALS as well as a rationale for use of CNTF to treat the same condition; opportunities for NGF as a medicine to treat drug-induced neurotoxicity and leprosy; and, gene therapy approaches for central nervous system disorders. < parts deleted > Other research presentations of interest will highlight: * The potential of SOD (superoxide dismutase) for therapy of ALS (Amyotrophic Lateral Sclerosis), < parts deleted > * A rationale for treatment of ALS with CNTF (ciliary neurotrophic factor), * Gene therapy approaches for central nervous system diseases, * Opportunities for nerve growth factor as a treatment for drug-induced neurotoxicity and leprosy. Less promising laboratory results have been seen for other neurotrophic factors as treatments for drug-induced neurotoxicity, including BDNF, CNTF and NT-3. As well, short-term clinical studies in the Parkinson's field indicate that the value D(1) agonists may not be as clear as originally thought. Amyotrophic Lateral Sclerosis (ALS) (Lou Gehrig's Disease): Superoxide dismutase (SOD) SOD ameliorates motor neuron disease in a preclinical model of ALS and could be a candidate for therapy. Administration of superoxide dismutase relative to control pairs of wobbler mice showed positive results in several respects: * improved grip strength up to three-fold (p<0.001) * improved muscle contracture in the forelimbs (p<0.001) * biceps muscle weight increased approximately 20% (p0.003), and * the degree of denervation atrophy in the biceps was inhibited. * Ciliary neurotrophic factor was shown to be reduced in patients with ALS compared to matched controls, depending upon location in the brain. Ciliary neurotrophic factor (CNTF) has been tested in clinical trials as a treatment for amyotrophic lateral sclerosis. Clinical trials sponsored by Regeneron have been halted because of untoward toxicity of the medicine administered at high dose levels. Clinical trials continue for a similar product sponsored by Synergen. A report at the 1994 meetings of the American Neurological Association will discuss the tissue levels of CNTF found in ALS patients compared to matched controls. Researchers report the first evidence of a change in CNTF levels in ALS patients providing some rationale for continuation of trials (see Table 1). Table 1 - CNTF Levels In ALS Patients Vs. Matched Controls 1994 Table 1 Ciliary Neurotrophic Factor (CNTF) in ALS patients versus matched controls Tissue CNTF concentration Ventral horn of spinal cord -75% p=0.001 Dorsal column small but significant change Dorsal horn small but significant change Lateral column no significant change Cerebral motor and occipital cortex no significant change Source: Annuals of Neurology, August 1994 Drug induced neurotoxicity * Neurotrophic growth factors do not have a general protective effect against neurotoxins like chemotherapeutic drugs, including brain-derived neurotrophic factor (BDNF), ciliary neurotrophic factor (CNTF) and neurotrophin-3. Nerve growth factor may have limited applicability. In a laboratory model (dorsal root ganglia exposure) several neurotrophic growth factors, including brain-derived neurotrophic factor (BDNF), ciliary neurotrophic factor (CNTF) and neurotrophin-3 (NT-3) were shown ineffective at preventing chemotherapy-associated toxicity with drugs such as cisplatin, suramin and vincristine. However, nerve growth factor (NGF) did ameliorate toxicity induced by suramin. Gene therapy * Adenovirus vectors may provide opportunities for gene therapy to treat central nervous system disorders. Gene therapy may be applicable for a number of inherited central nervous system diseases. However, technical issues with regard to gene therapy for CNS disease are significant. Limiting issues include: the blood-brain barrier which allows limited transport of blood-borne molecules, compartmentalization of the CNS into distinct cellular groups, and vulnerability of CNS tissue to direct injection. Researchers at the American Neurological Association meetings will review success with a replication-deficient recombinant adenovirus in expressing genes in motor and sensory neurons. < parts deleted > === end of als 140 ===