=============================================================== == == == ----------- ALS Interest Group ----------- == == ALS Digest (#96, 18 April 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 == == 230+ 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 .. MDA Research Report 2 .. Month 8 on Riluzole (maybe) 3 .. ALS Workshop in Philadelphia 4 .. Suctioning 5 .. need cDNA for the bcl-2 gene (1) ===== MDA Research Report ========== Date : 18 Apr 94 16:07:23 EDT >From : Barry Goldberg <71154.330@CompuServe.COM> Subject: MDA Research Report HIGHLIGHTS OF MOLECULAR MECHANISMS OF NEUROMUSCULAR DISEASE SYMPOSIUM Tucson, AZ January 24-25, 1994 "The MDA-sponsored symposium, Molecular Mechanisms of Neuromuscular Disease, was held January 24 and 25, 1994, in Tucson, Ariz. Nearly 200 attendees, physicians and scientists benefited from reports on the latest developments in the search for the causes of and treatments for the 40 neuromuscular diseases in MDA's program. This kind of symposium, an important tool for MDA, fosters cooperation and collaboration among researchers, speeding progress toward treatments and cures." This was the introductory paragraph of a multiple page document which summarized the presentations of leading physicians and scientists at the above symposium. For the sake of brevity, the information below is that which references motor neuron diseases such as ALS only. Information is also available on gene therapy, unstable DNA, ion channels and some other subjects. I will be happy to forward these if requested through bro. Thanks. "Motor Neuron Disease Motor neurons are nerve cells that control muscle cells via neurotransmitters. They're located in the brain and spinal cord. Amyotrophic lateral sclerosis (ALS, or Lou Gehrig's disease) is a disease of brain (upper) and spinal cord (lower) motor neurons. The spinal muscular atrophies (SMAs) mostly involve the spinal (lower) motor neurons. Stanley Appel of Baylor College of Medicine in Houston presented studies on the role of the immune system in ALS. About 10 percent of ALS is due to a genetic defect. The cause of the other 90 percent, called sporadic ALS, is uncertain. Appel's studies show that the immune system is probably attacking channels that permit passage of calcium into cells. These channels, called voltage-gated because they respond to changes in voltage, can be damaged by immune-system proteins in people with ALS. When damaged, they let in too much calcium, which kills cells. Appel and others have tried suppressing the immune system in people with ALS, but this has not been effective. Appel believes that nerve cells may be "marked" for death early in the autoimmune process and that immunosuppression as it is now practiced cannot save them. Appel's studies of calcium channels are made possible in part by a sophisticated imaging system known as a confocal laser microscope, purchased for his laboratory by MDA. Because of the imaging system and a supply of renewable nerve cells that his lab has developed, Appel expects to know soon exactly which calcium channels are abnormally opened in ALS and how the calcium kills cells. He can then begin to devise ways to prevent calcium "poisoning." Jeffrey Rothstein of Johns Hopkins University in Baltimore presented studies on the possible role of a neurotransmitter called glutamate in sporadic ALS. Rothstein's studies show that glutamate may be inadequately moved away from nerve cells after carrying a signal to them. This transport abnormality may cause a form of cell poisoning. Rothstein is testing different ways of protecting cells against excess glutamate. He believes that sporadic ALS has more than one cause. Jillian Parboosingh of Montreal General Hospital discussed findings in the genetic, or familial, form of ALS. Her group's studies are built on the 1993 discovery by MDA scientists that a gene for a protective enzyme called SOD1 is flawed in some people with genetic ALS. Robert Brown of Massachusetts General Hospital in Boston and Teepu Siddique of Northwestern University Medical School in Chicago headed the laboratories involved. Parboosingh reported that many different defects have been found in the SOD1 gene in people with ALS. None of the ALS patients her group looked at had defects in other genes for similar enzymes. However, a few people with ALS have been found to have defects in a gene for a neurofilament protein. Neurofilaments play a structural role in nerve cells. Brown reported his studies of SOD1 gene defects in familial ALS. He's been studying how the flawed SOD1 protein works and how it affects nerve cells. So far, the SOD1 defects studied seem to disrupt function of the SOD1 enzyme, resulting indirectly in a buildup of toxins in nerve cells. Brown believes there may also be defects that cause the SOD1 enzyme to damage cells directly. Brown identified gene defects in two cases of sporadic, or non-genetic, ALS. This shows that spontaneous gene defects can occur and don't have to be inherited from a parent. Siddique pointed out that ALS has varying ages of onset, usually late in life, even though the genetic defect is present from birth. He believes that different SOD1 defects may cause different rates of disease progression. He also believes there may be another gene that has a protective effect against SOD1 defects. Variations in this gene may affect the age of onset of ALS. Siddique's findings suggest there may be ALS "susceptibility" genes, which, though they may not directly cause ALS, may predispose some people to developing the disease. Kenneth Fischbeck of the University of Pennsylvania in Philadelphia discussed work in spinal-bulbar muscular atrophy, also known as X- linked SMA and Kennedy's disease. This disease, so far known to affect only males, occurs in adulthood and causes progressive muscle weakness along with symptoms of androgen deficiency, such as breast development and infertility. In 1991, Fischbeck's MDA-funded group discovered that the underlying cause of this disease is a defect in a gene for the androgen receptor, a protein that attaches to androgens and brings them into cells. Fischbeck's subsequent studies have found that the defect causes the androgen receptor to behave abnormally. Motor neurons are damaged in the process, and androgen activity is decreased. Fischbeck is continuing to study how the gene defect leads to the disease by trying to introduce the defect into mice. The type of defect involved is called an expanded triplet repeat. Jerry Mendell at Ohio State University in Columbus is starting an MDA- funded drug trial to test the effects on SBMA of blocking and adding androgens. T. Conrad Gilliam of Columbia University in New York reported his continuing search for the gene defect or defects for the childhood forms of spinal muscular atrophy (SMA). In 1990, Gilliam's MDA-backed group found that a genetic defect on chromosome 5 can cause SMA. To date, however, the precise defect has not been identified. Researchers believe that different defects on chromosome 5 result in different forms of the disease. These forms differ in severity and age of onset. A gene for a cell adhesion molecule, known to play a role in the development and maintenance of neurons, is a likely candidate for carrying SMA defects. Six other genes are under study as well." --- MDA -- Working to find the cure for neuromuscular disease --- (2) ===== Month 8 on Riluzole (maybe) ========== Date : Sun, 17 Apr 94 14:17:32 EDT >From : "Doug Jacobson" Subject: Month 8 on Riluzole (maybe) Friday (4/15/94) I had my 8-month checkup as a participant in the riluzole trial here in Houston. Aside from the fact that I had just dropped a BIG check in the mail to Unca Sam, I must say that, all in all, it was definitely a kick-butt kind of day. In the checkup, we go through a number of stations...medical history, survey, neurologist, lab work, and physical therapist. Most of it was status quo, then the neurologist said that he saw absolutely no progression, and, in his subjective opinion, a couple of areas seemed to show slight improvement. Cool... Then on down to PT for the strength tests. You know, raise your knee and don't let me push it down, raise your arm and don't let me bend it, cough, stick your tounge out (that one kills me, got me laughing so hard I couldn't whistle). Anyway, when all was said and done, and we compared with results from two months ago, I showed definite improvement in a number of upper body tests. Understand this please...not just "no progression", but improvement! They had theorized that the drug would take 6 - 12 months to build up, if I am on the drug (I think I am now!). My legs are still going south faster than I was hoping, but I have put it in motion to get a scooter, so I'll be mobile again. From my research, test drives, etc., I think that Electric Mobility and their Rascals are the best bang for the buck. Although they are expensive, they seem the best put together. I looked at Electric Mobility, Pride, Lark, and Amigo. If anyone else has comments or thinks I'm all wet, please let me know, I'm going to do something this week. Also, I may have seen this here, but in case I didn't, there is a meeting in Paris next month to review the results of the European trial, and preliminary results of the US trial. If it goes well, they are going to stop the trial early, and riluzole may be available in the States commercially by the end of the year. Like I said, it was definitely a kick-butt day! God bless you all, Doug (If life deals you a bad hand...bluff!) J. (3) ===== ALS Workshop in Philadelphia ========== Date : Mon, 18 Apr 94 10:19:47 EST >From : "Mike Doliton" Subject: Workshop in Philadelphia I just got back from an ALS workshop in Philadelphia. It was excellent. I want to thank any of the group that were there from Hahnaman ALS Clinic that are reading this bulletin. I aspecially found the session on the research interesting. Riluzole was mention along with CNTF, IGF-1, and BDNF. The doctor who spoke menting there wasn't enough reasearch being done on the upper motor neuron damage. Lots of attention being payed to the lower motor neuron damage. He said that a cocktail of BDNF and CNTF might really help but that it was nearly impossible due that competitive nature of the drug companies. We have to push Congress to push the drug companies to do the combined studies. I asked about the L-CHANNEL CALCIUM BLOCKER. He didn't know that much about this but he definately knew that too much calcium was bad along with too much Glutamate which Riluzole and perhaps Neurontin help with. He mentioned that there was a critical balance of chemicals (Glutamate, Calcium, Free Radicals and Superoxide Dismutase) in the Synapse. He brought out the fact that we need Glutamate but in the right quantity. Glutamate is a chemical messenger. So when we take drugs that are glutamate blockers we better be careful we don't take too much of it or the message won't get through to the muscle. Also I have been reading more and more that Riluzole is helping people even improving them in certain areas. The note from Doug Jacobson proves this out. He mentioned he was "status quo, then the neurologist said that he saw absolutely no progression, and, in his subjective opinion, a couple of areas seemed to show slight improvement". That's great news from an actual patient. Thanks Doug for sharing this with us. I am checking into the use of Neurontin. I am going to call the MDA clinic in Secaucus, NJ. A bulletin came out from the MDA stating that some people on Prodigy were mentioning the use of Neurontin as a Glutamate blocker. They wanted to stear people to their local MDA clinic physician. That is what I am doing. Oh, by the way. I think the scooter is a fantastic aid. I think it is better than a wheel chair in that it doesn't have the stigma of the handicapped. I also saw a crane like aid that lifts the patient very easily and rolls along the floor. That's it for now. Regards, Michael R. Doliton Sony Medical Systems Division (4) ===== Suctioning ========== Date : 14 Apr 94 15:29:43 EDT >From : Greg Trautman <72262.1664@CompuServe.COM> Subject: Suctioning The following article was published in the February issue of Nursing94. It may be of interest to recipients of the ALS Digest. Suctioning Hazards of Saline Bolus If you routinely instill a saline bolus to thin or loosen secretions before suctioning a patient, consider this: A nurse-researcher now says the practice has an adverse effect on the SaO2 (saturated oxygen) level. Not only that, the SaO2 continues to deteriorate over time. Michael H. Ackerman, RN, CCRN, DNS, Veterans Affairs Medical Center and the School of Nursing, State University of New York at Buffalo, and his team studied 40 critically ill male patients ages 45 and over. They checked the patients' SaO2 levels every minute for 5 minutes after a saline bolus was instilled into an endotracheal or tracheal tube. Across the board, the SaO2 dropped significantly. Saline (or any fluid) may impede gas exchange Ackerman says. If that isn't enough to convince you, Ackerman also says that the rationale for instilling saline before suctioning is a myth: There's no evidence that it thins or loosens secretions. Source American Journal of Critical Care July 1993 Greg Trautman trautman@ohsu.edu Compuserve: 72262,1664 (5) ===== need cDNA for the bcl-2 gene ========== Topic 1127 bcl-2 cDNA bionet.neuroscience 1:25 am Apr 16, 1994 >From: springerj@HAL.HAHNEMANN.EDU) I am interested in obtaining the cDNA for the bcl-2 gene for use in studying amyotrophic lateral sclerosis (ALS). Please send info to my e-mail address: springerj@hal.hahnemann.edu. Thanks Joe e. Springer, Department of Neurology Hahnemann University Philadelphia, PA 19102 == end of als 96 ==