Date: Wed, 2 Nov 94 15:12:25 EST From: Bob Broedel To: Stuart.Neilson@brunel.ac.uk Subject: Re: ALS Interest Group List =============================================================== == == == ----------- ALS Interest Group ----------- == == ALS Digest (#133, 07 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 == == 360+ 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 .. The Jackson Lab & ALS 2 .. CHANGE: HMATRIX-L 3 .. MDA Research Report #51 (1) ===== The Jackson Lab & ALS ========= GENETIC RESEARCH NEWS TIPS FROM THE JACKSON LABORATORY, BAR HARBOR, MAINE BAR HARBOR, Maine, Sept. 28 /PRNewswire/ -- The AIDS Vaccine: TJL Mice Likely To Pioneer The Way When better and safer AIDS vaccines are made for humans it is likely that testing with research mice from The Jackson Laboratory will provide the breakthroughs. New TJL mouse models that accept human cells and develop a complete human immune system are now beginning to enable researchers to study HIV infections in mice that closely resemble the progress of the disease in humans. Historically, having an animal model for a disease has meant a speeding up of the research process as much as ten-fold. Suspended Animation: 1,000,000th Mouse Embryo Frozen Most people think of it as a science fiction theory that is played out only in movies and novels: What if we could freeze life in its steps only to resume it again at a later time? Cryopreservation of life is a daily reality at The Jackson Laboratory as mouse embyros are frozen and stored at -196 degrees Celsius and later brought back as live mice. Some have been frozen for nearly 15 years. The Laboratory recently cryopreserved its one-millionth living mouse embryo. Since 1978, the Lab has pioneered this type of cryopreservation of mice. Today, there are many types of research mice that exist nowhere else on Earth except in TJL freezers. If Mice Get Osteoporosis Osteoporosis researchers at The Jackson Laboratory are seeking to identify genes in humans that regulate bone density by first finding the genes in mice with osteoporosis. This research represents a significant step to development of effective diagnostic, predictive and therapeutic approaches to bone density loss. Osteoporosis affects approximately 14 million Americans. Studies are looking at whether age-related bone loss is genetically regulated through comparisons of the rates of bone loss among inbred strains of mice. Mice are remarkably close to humans genetically with some reports noting an 85 percent or better relationship between the mouse and human genes. CONTACT: Jeff Witherly, or Grady Holloway, or Galen Perry of Jackson Laboratory, 207-288-3371 Internet e-mail: jlw@jax.org, ghh@jax.org, gpp@jax.org ===== = The following is reprinted from LINK (Fall 1994, Vol. 8, No. 2). = = ALSA funding mouse model development. = = Through the support of the ALS Association's Greater Philadelphia = Chapter, ALS researchers will be assured of a supply of the new = transgenic mice expressing a mutant form of CuZn SOD. The ALS Association's = grant to The Jackson Laboratory, world renowned genetics facility in = Bar Harbor, Maine, will help to secure, colonize and distribute the new = mice models to ALS researchers. The genetically engineered mice models = will be a key tool in studying ALS and will offer opportunities to test = therapies. ===== (2) ===== CHANGE: HMATRIX-L ========== Date : Thu, 6 Oct 1994 13:27:29 CDT Sender : NEW-LIST - New List Announcements >From : Lee Hancock Subject: CHANGE: HMATRIX-L HMATRIX-L, a discussion group concerning online health resources, has moved to Listserv@kumchttp.mc.ukans.edu. To subscribe send an email message to Listserv@KUMCHTTP.MC.UKANS.EDU with the following in the BODY: SUBSCRIBE HMATRIX-L YOUR_NAME ======================================================================== Lee Hancock || Archie R. Dykes Library Educational Technologist || 3901 Rainbow Blvd. University of Kansas Medical Center || Kansas City, KS 66160-7181 || (913) 588-7144 Bitnet - LE07144@UKANVM || Internet - LE07144@UKANVM.CC.UKANS.EDU || "Knowledge is nothing if not || shared"... Me Owner & Editor: Internet/BitNet Health Science Resources List Owner CPRI-L (Listserv@kumchttp.mc.ukans.edu) Computerized Pt. records HMATRIX-L (Listserv@kumchttp.mc.ukans.edu) Online Health Resources ========================================================================= (3) ===== MDA Research Report #51 ========== Date : 07 Oct 94 00:47:50 EDT >From : Barry Goldberg <71154.330@compuserve.com> Subject: MDA Research Report #51 Once again I apologize for being so late in distributing this information to you. But here is Report #51 from August -- MDA-supported researchers, studying the cause of familial amyotrophic lateral sclerosis (FALS), have been evaluating the effects of defective SOD1 in laboratory experiments. SOD1 functions as a manager of potentially toxic free radical by- products of some chemical reactions that occur in the body. Analysis of SOD1 gene defects associated with FALS shows that the resultant defective SOD1 protein enzyme has a reduced ability to function properly. In fact, a certain type of defect appears to result in the most clinically severe cases. The activity of the SOD1 in these individuals was reduced by 50% compared to persons with sporadic or nonfamilial ALS who have a normal level of SOD1 activity. Why the SOD1 defect causes motor neuron death is still unexplained, and the researchers suggest that the reduced activity of SOD1 or a possible acquired toxic function of the defective SOD1 may be involved. (Rosen, D.R. et al., Human Molecular Genetics 1994; 3:981-987). In experiments performed by another research group the activity of SOD1 was reduced from 20-50% depending on the particular defect in the SOD1 enzyme. The scientists propose that even slight losses in SOD1 function may result in motor neuron death, or defective SOD1 may possibly gain an ability to damage motor neurons in a manner having little to do with its role in the management of free radicals. (Borchelt, D.R. et al., Proceedings of the National Academy of Sciences, USA 1994; 91:8292-8296). That neurodegeneration may result from free radical damage is suggested by the data concerning association of familial amyotrophic lateral sclerosis (FALS) with defective SOD1. The mechanism of cell death that results from reduced activity of SOD1 is being studied in cells grown in a culture dish. When researchers inhibited SOD1 production the cells began to die and the dying cells were rescued with vitamin E which would indicate that a free-radical-based mechanism of cell death is involved. The combination of vitamin E and a nerve growth factor (NGF) was found to be protective for cells with inhibited SOD1, whereas NGF alone was not protective. Whether or not the cell culture model studied can be related to FALS is unknown. Cells in culture are generally much more responsive to factors in their surroundings than cells that are within tissues in the body. (Troy, C.M. and Shelanski, M.L., Proceedings of the National Academy of Sciences, USA 1994; 91:6384-6387). Evidence that the enterovirus is present in the spinal cords of individuals with motor neuron disease was recently presented by researchers located in Scotland. Over a ten-year period spinal cord tissue samples were obtained from individuals with sporadic or familial motor neuron disease and these were compared to samples from persons who were not affected by a neurodegenerative disorder. Only the enterovirus genetic material--not intact enterovirus--was detected. The analyzed genetic material is apparently closely related to cocksackie type B virus but not to poliovirus. The fact that no infectious virus was found could indicate that a persistent, low level infection is responsible. Further study of the viral genetic material and of the mechanisms by which such a virus may cause motor neuron disease is being conducted by the research group in order to determine the possible causative role of viruses in amyotrophic lateral sclerosis (ALS). (Woodall, C.J. et al. BMJ 1994; 308:1541-1543). The potential benefit of ciliary neurotrophic factor (CNTF) therapy in motor neuron disease was evaluated in a mouse model called the wobbler mouse, which is not considered to be a specific model of amyotrophic lateral sclerosis (ALS). In the wobbler mouse CNTF was found to slow the disease progression and improve muscle strength. The researchers conclude that the benefits observed may be a result of CNTF acting on muscle as well as nerves. There are three different mouse models of motor neuron disease -- wobbler, MND and PMN -- that each benefit from the administration of CNTF. (Mitsumoto, H. et al., Annals of Neurology 1994; 36:142-148). Some CNTF studies to date have indicated that CNTF may be effective as a therapy for motor neuron disease while other experiments indicate that it may not be clinically useful. Researchers believe that the evaluation of the ability of CNTF to slow progression of ALS in humans will be complex. (Longo, F.M., Annals of Neurology 1994; 36:125-127). The gene defect associated with facioscapulohumeral muscular dystrophy (FSHD) is known to be located in a specific region on chromosome 4. A certain rearrangement of a section of DNA from this chromosomal area was detected in some cases of FSHD. A probe called p13E-11 is used to look for the rearrangement, however, further research is demonstrating that caution must be used. Molecular geneticists are suggesting that the probe cannot be utilized for diagnosis without additional genetic linkage information. (Deidda, G.C. et al. Annals of Neurology 1994; 36:117-118). A recent case report describing an individual with a mitochondrial myopathy demonstrates the high degree of variability clinically observed with this class of disorders. Various types of genetic defects associated with the class can result in a number of different clinical features. Physicians describe a woman whom they suspected, due to the presence of lipomas and deafness, had a type of mitochondrial disorder called MERRF. The emphasis of the report is on the importance of lipomas in diagnosis of mitochondrial myopathies. (Calabresi, P.A. et al. Muscle & Nerve 1994;17:943- 945). A small percentage of individuals affected by myasthenia gravis (MG) have thymomas. The autoimmune response in these people is generally due to an abnormal immune reaction to one of several skeletal muscle proteins. The ryanodine receptor (RyR), a type of calcium channel that controls the flow of calcium in skeletal muscle cells, is the target for the autoimmune response seen in about half of the individuals with MG who have thymomas. The researchers conclude from their observations that MG with thymoma poses a high risk for the development of severe, fatal MG. The physicians suggest close management and vigorous treatment for these individuals. (Mygland, A. et al. Journal of Neurology, Neurosurgery, and Psychiatry 1994; 57:843-846). Virtually each case of congenital myotonic dystrophy (DM) has been reported to be inherited from an affected mother. However, MDA- supported researchers recently described the appearance of congenital DM when the disease had been inherited from a mildly- affected father. Congenital DM is the most severe form of the disorder and is generally associated with a large, expanded repeat segment of DNA in the DM gene. The observation provides evidence that exposure to maternal factors during development in the womb is not necessarily associated with congenital DM. For genetic counseling it should be kept in mind that it is possible for large repeats of unstable DNA to be passed on from the father. (Bergoffen, J. et al. Journal of Medical Genetics 1994; 31:518- 520). Limb-girdle muscular dystrophy (LGMD) researchers have isolated a fragment of chromosome 15 in which they expect to find the disease gene for one form of autosomal recessive LGMD (LGMD2). The scientists will be working to narrow the region where the gene appears to lie and this work will lead them to isolating the gene that is defective in individuals with LGMD2. (Fougerousse, F. et al. Human Molecular Genetics 1994; 3:285-293). Other researchers have studied two large families affected by an autosomal recessive form of LGMD that does not appear to result from defects in a gene located on chromosome 15. These individuals have LGMD due to a defective gene on chromosome 2. By identifying the genes involved in the various forms of LGMD the disease mechanism can be understood. (Bashir, R. et al. Human Molecular Genetics 1994; 3:455-457). Late onset Friedreich's ataxia generally occurs from between 21 to 36 years of age; typical onset is before age 20. Molecular geneticists expect to find the Friedreich's ataxia gene for both the typical and late onset forms on chromosome 9. Clinically, the different types of the disease are similar except that the late onset form has a slower progression and is considered to have a milder course. Researchers are still not certain if different defects in the same gene are responsible for the two forms of Friedreich's ataxia or whether different combinations of effects may be involved. (De Michele, G. et al. Journal of Neurology, Neurosurgery, and Psychiatry 1994; 57:977-979). Researchers are closing in on the identification of the defective gene that causes Friedreich's ataxia (FA). The area on chromosome 9 that is expected to contain the gene has been narrowed such that geneticists are now analyzing specific genes in the region. Three genes in this area were recently determined not to be involved with FA, and the work has reduced even further the area in which the scientists will have to look for the FA gene. (Duclos, F. et al. Human Molecular Genetics 1994; 3:909-914). Lambert-Eaton syndrome (LES) appears to result from an autoimmune response to a part of the calcium channel which is located at the neuromuscular junction (NMJ), where nerve and muscle meet. A high percentage of individuals affected by LES have what is called small cell carcinoma of the lung. The connection between these two conditions is not well understood. One proposal is that a component on the surface of the cancer cells is also located at the NMJ. An immune response to the cancer could produce antibodies to this shared component leading to an unwanted attack on the NMJ. MDA researchers recently reported supporting evidence that antibodies, which are apparently produced to fight the tumor, recognize calcium channels on the cancer cells and end up also attacking the calcium channel located at the NMJ. In fact, there appears to be additional components on the surface of the small cell carcinoma that are also found at the NMJ and they may be involved in the disease process also. (Morton, M. E. et al. Journal of the Federation of American Societies for Experimental Biology [FASEB J] 1994; 8:884-888). Announcements An International Registry for Pompe's Disease (type II glycogen storage disease, acid maltase deficiency) is currently being established. The purpose of the registry is to identify individuals with the juvenile and the adult forms of the disease who would be candidates for a clinical trial/therapy should one be initiated. Currently, research for Pompe's disease is focused on enzyme replacement therapy and an efficient system which is able to produce active human acid glucosidase has been developed. Clinical trials are anticipated to begin within one to two years. Participation in the registry requires providing: copies of pertinent medical records; a brief clinical history; and physician and participant contact information. To be listed in the Pompe's Disease registry or to inquire further please contact: Allyn McConkie-Rosell or Y. T. Chen, M.D., Ph.D., Division of Medical Genetics, Duke University Medical Center, Durham, North Carolina 27710. 919-684-2036, fax 919-684-8944. cc: MD Forum [MD-LIST@DATA.BASIX.COM] --- MDA -- Working to find the cure for neuromuscular disease === end of als 133 ===