Date: Mon, 18 Dec 95 13:18:05 EST From: Bob Broedel To: Stuart.Neilson@brunel.ac.uk Subject: Re: ALSD231 ALS-ON-LINE =============================================================== == == == ----------- ALS Interest Group ----------- == == ALS Digest (#227, 28 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 == == 1250+ 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 .. ALS in not a fatal disease! 2 .. BDNF/Neurontin/ seeking info & contacts 3 .. Seeking further information about ALS 4 .. MDA Research Report #60 (1) ===== ALS is not a fatal disease! ========== Date : Wed, 8 Nov 1995 21:19:28 -0800 >From : eaopp@ucla.edu (Edward Anthony Oppenheimer, M.D.) Subject: ALS is not a fatal disease! Dear Bob ... ALS is not a fatal disease! ~~~~~~~~~~~~~~~~~~~~~ In the last issue of ALSD223 ALS-ON-LINE (7 Nov 95) you included item #9, an article from The Grand Rapids Press, based on information from the West Michigan ALS Association. Parts are copied below. This again spreads misinformation about ALS, stating that it is a "fatal" disease. Later on other statements in the article are more accurate: that average life expectancy with ALS varies... The words we use can change people's lives. People with ALS should have choices, however this requires accurate information: Should I continue living with ALS?, or ...Should I accept death due to complications of ALS? These complications (the most common are: respiratory failure, infection, and malnutrition) are not ALS itself, and can be successfully treated. Many people give up hope because they are told that ALS is fatal; this is not true. When people are given this misinformation from the time of diagnosis, they are deprived of hope and deprived of choice. This increases the likelihood of depression, feelings of abandonment and limited options. Shouldn't we provide people with ALS, and the public, with better information? This is not said in order to advise people to always aggressively treat complications of ALS. But be sure, if you have ALS, that you know you have choices; know the pros and cons of each option depending on your individual findings and circumstances. Certainly palliative care is an important option. In 1995 it is unethical to say that ALS is a fatal disease. People with ALS and their family can make good decisions when healthcare professionals provide good information, good advice, and good care. Sincerely, Edward Anthony Oppenheimer, M.D. >========= Excerpts from item #9 of ALSD223 ALS-ON-LINE =======>> >DATE : 10/29/95 >SOURCE: The Grand Rapids Press > First described in detail by noted French physician Jean-Martin >Charcot in 1869, ALS is a progressive, fatal, neurological disease >that attacks nerve cells in the brain and spinal cord. Characterized >by a deterioration of motor cells in the spinal cord and brain, the >disease leads to muscle weakness which may affect hands, feet, legs, >arms, tongue and other muscles. ...... > ALS can affect anyone, however, first symptoms most often >appear between the ages of 40 and 70 years. Upon diagnosis with >ALS, the average life expectancy is three to fours years, but some >individuals remain active for 10, 15 or more years with short >periods of apparent respite from the disease. (2) ===== BDNF/Neurontin/ seeking info & contacts ========== Date : Sat, 7 Oct 1995 00:10:56 -0400 >From : RWidner@aol.com Subject: ALS Digest My wife, Sherry, was diagnosed with ALS in April of this year. Since then, we have been visiting the Neurology Clinic at the University of Utah every 3 months. Most recently, Sherry was accepted into a drug trial for BDNF, a nerutrophic growth factor. We are interested to know if you know of any other participants in this trial. Sherry is also taking Neurontin (gabapentin) and we are interested in any news regarding this drug. Finally, we would love to hear about any alternative treatments that have been successful with other patients. My wife and I live in Boise, Idaho and would be interested in having contact with others in the region. Thanks, Roger and Sherry Widner rwidner@aol.com (3) ===== Seeking further information about ALS ========== Date : Wed, 15 Nov 1995 16:23:52 -0800 >From : sci@rose.cnc.ac.cn (CHINA) Subject: Seeking further information about ALS We would like to have further information, as follows: 1. How are the affectiveness of the ALS trials that were conducted in the U.S.A? 2. How many drugs that may be effective for ALS disease are under production and/or being researched? What are their effectiveness? 3. Do any drug companies have their drugs on sale? 4. How can we purchase drugs we need from the U.S.A? ... or elsewhere? Thanks a lot! Regards. From sci@rose.cnc.ac.cn (4) ===== MDA Research Report #60 ========== Date : 27 Nov 95 16:51:52 EST >From : Barry Goldberg <71154.330@compuserve.com> Subject: MDA Research Report #60 Here's the latest research report from the Muscular Dystrophy Association issued to its clinic directors. I hope you find something of interest in it for you. MDA STAFF RESEARCH UPDATE -- SRU #60 -- 11/20/95 ************************************************ LIMB-GIRDLE MUSCULAR DYSTROPHY (LGMD) describes a group of disorders with similar clinical features and MDA researchers are discovering that the various forms of LGMD are caused by defects in different genes. The gene defects associated with LGMD type 2A (LGMD2A) and LGMD type 2D (LGMD2D) have already been identified. Now three separate research groups have found the defective genes responsible for two other forms of LGMD named LGMD2C and LGMD2E. These forms of LGMD, as well as LGMD2D, result from defects in three different dystrophin associated glycoproteins (DAGs). Along with dystrophin and other proteins, DAGs form a complex that most likely has as its primary role the stabilization of the muscle cell membrane by linking the structural components inside the cell with those outside. It appears that when any of the components of the complex are missing or not fully functional the complex as a whole cannot function which results in a form of muscular dystrophy. In addition to these LGMDs, Duchenne and BECKER muscular dystrophy (DMD and BMD) as well as a form of CONGENITAL muscular dystrophy (CMD) are associated with defects in the dystrophin-glycoprotein complex. DMD and BMD result from defects in dystrophin and CMD can result from defects in a protein called merosin located outside the muscle cell, which links to a DAG. A majority of the components in the dystrophin-glycoprotein complex were not previously known to exist and researchers are now establishing names for these new proteins. The dystrophin-glycoprotein complex is composed of: dystrophin, which is located just inside the muscle cell membrane; dystroglycans (a and b) and sarcoglycans (a, b and g) that make up the complex straddling the muscle cell membrane; and merosin, which is a part of laminin located outside muscle cells. (Lim, L. et al. Nature Genetics 1995; 11:257-264; Bonnemann, C. G. et al., Nature Genetics 1995; 11:266-273; Noguchi, S. et al. Science 1995; 270:819-822; and Worton, R. Science 1995; 270:755-756). The MYOTONIC DYSTROPHY (DM) gene defect is an unstable segment of DNA often called the CTG repeat expansion which is located in a gene called DMPK. Researchers have observed that the size of the CTG repeat, along with the severity of the disease, can increase with successive generations within a family, and they would like to define how the repeat size may relate to the severity of the clinical signs of DM. An MDA-supported research group recently found in one large family affected by the disorder that certain cardiac effects could be associated with the size of the CTG repeat expansion. Therefore, the researchers believe that CTG repeat size may be an accurate predictor of the degree of cardiac dysfunction in DM. (Totgozoglu, L.S., et al. Journal American Medical Association 1995; 274:813-819). How the repeat defect in the DMPK gene causes myotonic dystrophy (DM) has yet to be defined by MDA researchers. The CTG repeat defect may affect the DMPK gene or it could also affect other genes nearby. Apparently, the defect does not alter the structure of the DMPK protein but may lead to a reduction in the amount of message from the DMPK gene that is available to make the protein. It is also possible that the enlarged repeat changes expression of the surrounding genes. In the area near one end of the DMPK gene is a gene called 59, and another gene has just been discovered close by at the opposite end of the DMPK gene which has been named DMAHP. The gene 59 is expressed in brain and testis while DMAHP is expressed in tissues throughout the body. Although questions remain, the researchers propose that the size of the repeat expansion could lead to changes, of varying degrees, in the expression of any of the genes in the region, which could explain the variation of clinical signs seen with DM. (Boucher, C. A. et al. Human Molecular Genetics 1995; 4:1919-1925). Another human MYOBLAST TRANSFER trial has demonstrated the need for further work in the laboratory to explore what methods may be necessary to make myoblast transfer a successful technique for providing functional genes to defective muscle in humans. A recent report from an MDA-supported group showed that certain changes in the procedure, as compared to previous trials, were not sufficient to improve myoblast transfer in boys with Duchenne muscular dystrophy (DMD). The major difference involved the transfer of muscle cells from donor to host. Instead of transferring donor muscle cells to the boy with DMD only one time, myoblasts were transferred once a month for six months. No therapeutic benefit was observed, and the clinical researchers believe that the factors affecting the efficiency of myoblast transfer must be defined before the procedure can be improved. (Mendell, J. R. et al. The New England Journal of Medicine 333:832-838). DUCHENNE MUSCULAR DYSTROPHY (DMD) researchers have looked at the extent to which reversion occurs in the disease. Reversion is apparently a chance event that can take place in genes. An abnormal gene essentially reverts such that it becomes normal, or more similar to a normally functioning gene. For instance, a defect in the dystrophin gene, through reversion, may be eliminated and allow the gene to then produce a functional dystrophin protein. DMD muscle biopsies have been shown to contain muscle fibers with dystrophin in varying amounts that seem to exist as a result of such a reversion event. The presence of reverted muscle fibers is apparently not connected to the type of dystrophin gene defect, however, reversion cases in individuals with a duplication of a dystrophin gene segment appeared to be more frequent. Unfortunately, the small number of reverted muscle fibers that contain functional dystrophin are not sufficient to change the clinical presentation of DMD. The results support the evidence that indicates if gene therapy is to work a large proportion of muscle cells/fibers must acquire the functional gene. (Fanin, M. et al Muscle and Nerve 1995; 18:1115-1120). The form of CHARCOT-MARIE-TOOTH disease (CMT) that results from defects in the connexin 32 gene located on the X chromosome can be associated with an alteration in any one of several areas within the gene. In a study of 39 families it was found that defects could occur in almost any region of connexin 32, which most likely means that all regions of connexin 32 are important for the protein's function. The mechanism behind X-linked CMT is still unknown although analysis of the protein defects and the associated clinical signs of the disease may reveal what the cause of the disorder is at the protein level. (Bone, L. J. et al. Neurology 1995; 1863-1866). There are several types of Charcot-Marie-Tooth disease (CMT) that have been described. However, researchers have identified a family that has been difficult to diagnose. The specific form of CMT that the family is affected by is unknown. Their disease, diagnosed at birth or within a few years from birth, is slowly progressive, linked to the X chromosome and associated with deafness and mental retardation. The scientists believe that this form of CMT is genetically and clinically distinct from those previously identified. Further genetic studies of the family as well as the addition of new families to the study will help researchers find the defective gene responsible for the disease. (Priest, J. M. et al. Genomics 29:409-412). Charcot-Marie-Tooth disease type 2 (CMT2) does not occur as frequently as CMT type 1 (CMT1) and, clinically, the two forms of CMT are characterized differently. Previous studies of certain families with CMT2 have shown that a defective gene will be found on chromosome 1 that is associated with the disorder -- called CMT2A. However, not all individuals diagnosed with CMT2 can be linked to this same genetic area. Recent research on one large family affected by CMT2 has shown that a region on chromosome 3 contains the key to the genetic defect associated with this form of CMT -- named CMT2B. It is apparent that a number of different genes are associated with the different forms of CMT, however, the genes that are defective in either CMT2A or CMT2B have not been identified yet. (Kwon, J.M. et al. American Journal of Human Genetics 57:853-858). Three clinical forms of ACID MALTASE DEFICIENCY (AMD) or GLYCOGEN STORAGE DISEASE type II (GSDII) are defined. The infantile form has severe myopathy with rapid progression and an early onset while the juvenile and adult forms have a delayed onset, slow progression and a lack of cardiac involvement. Defects in a gene for a-glucosidase, which is an enzyme that is part of the pathway of reactions that provides energy for tissues such as muscle, are associated with the forms of GSDII. Recent work indicates that genetic analysis of the GSDII defects may be a helpful part of diagnosis to determine an individual's form of GSDII. (Poenaru, L. et al. Journal of Medical Genetics 32:836-837). Varying degrees of severity primarily define the three forms of SPINAL MUSCULAR DYSTROPHY (SMA). The defective gene responsible for SMA is known to be located in a certain region on chromosome 5 and genes have been described that are candidates for the SMA disease gene. One gene called NAIP is found defective in some cases of SMA, however, the data indicates that defects in NAIP may not be necessary for SMA to occur. Another gene called SMN is defective in a large majority of cases examined, although recent analyses of families from Germany and The Netherlands revealed that some individuals with defects in the SMN gene were not affected by SMA. Due to the lack of a definitive association of a particular gene defect with all forms of SMA, researchers conclude that the defective genes or mechanisms affecting the genes that are necessary to cause SMA have yet to be determined. (Hahnen, E., et al. Human Molecular Genetics 1995; 4:1927-1933 and Cobben, J. M. et al. American Journal of Human Genetics 1995; 57:805-808). To date, seven different defects within the emerin gene have been discovered to be associated with EMERY DREIFUSS MUSCULAR DYSTROPHY (EDMD). Analyses of the gene have shown that emerin is expressed throughout the body and a deficiency of the protein in heart and skeletal muscle appears to cause EDMD. In fact, female carriers of the disease may have cardiac problems as well. Other tissues do not appear to be affected to a noticeable degree by a loss of emerin. EDMD is a rare X-linked disorder, however, there are families in which the inheritance of the disease indicates that the X chromosome is not involved. Recent emerin gene studies confirmed that there is a distinct form of the disorder that is not associated with defects in the emerin gene. (Klauck, S. M. et al. Human Molecular Genetics 1995; 4:1853-1857; Bione, S. et al. Human Molecular Genetics 1995; 4:1859-1863 and Nigro, V. et al. Human Molecular Genetics 1995; 4:2003-2004). MDA researchers are narrowing the region on chromosome 9 in which they expect to find the gene that is defective in FRIEDREICH'S ATAXIA (FA). The critical region has now been isolated and manipulated in the laboratory such that more specific analyses can be performed to locate genes that could be involved. This is a critical advance toward the identification of the disease gene. (Montermini, L. et al. American Journal of Human Genetics 1995; 57:1061-1067). --- MDA -- Working to find the cure for neuromuscular disease --- === end of als 227 ===