=============================================================== == == == ----------- ALS INTEREST GROUP ----------- == == ALS Digest (#28, 08 MAR 1993) == == == == To subscribe, to unsubscribe, to request back issues, == == to contribute notes to ALS Digest, etc. please send == == e-mail to: == == bro@huey.met.fsu.edu (Bob Broedel) == == == == All interested people may "broadcast" messages to == == to ALS Digest subscribers by sending to: == == als@huey.met.fsu.edu == == == == P.S. ... March 8th is International Women's Day == =============================================================== (1) ===== Building the international ALS e-mail network ========== ----- Date : Fri, 5 Mar 93 10:02:56 -0800 From : Cathy Britell To : broedel@geomag.gly.fsu.edu Subject: ALS Network Dear Bob, I reviewed your letter with great interest. We have an assistive technology center here at RCH, a vocational institute for individiauls with disabilities, and are always interested in sharing whatever information and/or expertise we have. I have worked with a number of individuals with ALS in computer access and communication, and have found it very rewarding (I sometimes wonder if the genetic locus for ALS is not the same as that for niceness). We are also interested in exploring all the possibilities of internetworking for consumers and professionals re: disability issues, though we are new to this area and just beginning to figure out the "systems" out there on the "edge of cyberspace". Catherine W. Britell, M.D. Director of Assistive Technology RCH Vocational Institute ----- Date : Mon, 08 Mar 93 00:07:49 MET From : Jurek Subject: ALS To : Bob Hello Bob, I am neurologist interested in your group. Could you add me to ALS Digest subscribers? Thanks. Send me if at all possible back issues. Recently we have had some strange cases of ALS in our area where the senation problems were quite visible. Anyway, I would like to keep in touch with this group. Cheers from Poland. Jerzy Krupinski,MD , Institue of Neurology, Cracow,Poland, fax:(4812)213976 (2) ===== help request ========== Date : Sun, 7 Mar 93 20:51:22 PST To : bro@huey.met.fsu.edu From : "R. D. HESS" Subject: ALS Interest Group I'm an ALS patient (progressive bulbar palsy, now spreading to areas outside the vocal zone) seeking information about medication. My treatment is supervised by local physicians (neurologist, pulmonary specialist) and the director of the ALS Research Foundation in San Francisco. Dealing with saliva has been a problem; a major threat is accumulation of mucus in the trachea. The possibility of suffocation is not remote. I've been given a prescription of Robinul to help reduce saliva production. After a couple of episodes of choking on mucus (I use a suction machine to clear the throat), a differnt physician prescribed Iophen (Organidin) to loosen secretions in the throat and make them easier to remove. I do this myself; still have almost normal strenght in arms. It seems possible that these two drugs work in opposite directions--one to reduce secretions, the other to increase them. My question is where I might get information about the effects of each and the consequences of taking them simultaneously. Both have been prescribed. I am on good terms with my physicians, so no games are being played here. I seek more complete information that may be available to them in the huge books on drugs they keep at hand. Suggestions of any helpful steps I might take would of course be welcome. I will take them to my physicians for consideration. I hope this sort of thing falls within the scope of our ALS Interest Group network. Bob (3) ===== News ========== Washington Post 08 MAR 1993 Filling in Gene Map, But Far From Home; Rapid Gains in Identifying Disease Sources Raise False Hope That Cures Are Imminent By David Brown, Washington Post Staff Writer Two weeks ago it was the news that scientists had tentatively identified a gene responsible for adrenoleukodystrophy, the rare disease of "Lorenzo's Oil" fame. Last week, location of a gene linked to Lou Gehrig's disease made the national news. Who knows what's in store tomorrow? Gene discovery is growing exponentially. There are between 50,000 and 100,000 human genes; and as of last week, 2,736 of them had been "mapped" - located precisely on one of the 24 human chromosomes - according to the Genome Data Base, an international gene registry at Johns Hopkins Hospital. Of those, 682 are known to be associated with human disease when they occur in mutant form. In 321, researchers have decoded at least part of the "sequence," or precise chemical structure, which is the first step in determining precisely how a gene works. This knowledge will only grow faster in the years ahead: As with jigsaw puzzles, the pieces get easier to find once you've already got a lot of them in place. When a "disease gene" is discovered, the news is often accompanied by the suggestion that treatments are now, consequently, within sight. But knowing the mechanism of a disease is far from knowing how to alter that mechanism; and even well-documented genetic problems will pose formidable obstacles to those seeking a cure. That is because, as a piece of engineering, the human body is the most complicated and compartmentalized machine on earth. And treatments involving genes - or the products of genes - require tinkering with the machine's most maddeningly hard-to-reach parts. "With genetic knowledge, you are giving yourself a fighting chance of getting therapies. But it's a whole different thing actually coming up with a therapy," Peter L. Pearson, the scientist in charge of the Genome Data Base, said last week. "In many ways, what is going on now - isolating and characterizing genes - that is the easy bit of it. Not Necessarily Heritable "Genetic disease" suggests an affliction that can be passed from one generation to the next, but in fact many diseases are genetic without being heritable in any obvious sense. For example, cancer arises when one or more genes regulating cell growth are damaged, and thus has a "genetic" origin. In most cases, however, cancer is not inherited because the crucial mutation occurs after birth. Even many chronic illneses, such as coronary artery disease and hypertension, are genetic to the extent that many genes acting together, and with the environment, determine the chances that a person will develop the condition. Genes carry the instructions for making proteins, a biochemical family whose members have a few common characteristics, but are otherwise nearly infinite in variety. Each protein has a precise function, doing a single job and (in most cases) perturbing the environment very little. Equally important, proteins act in particular locales - not just specific organs, but specific cells and specific parts of cells. Most therapeutic drugs - even the "wonder drugs" of contemporary medicine - ignore that kind of molecular precision. The object is to get the medication into the bloodstream, which carries it to the few places where it's needed - and the many places where it isn't. Cancer drugs kill both rapidly dividing tumor cells and rapidly dividing follicle cells, which is why chemotherapy patients often lose their hair. Aspirin relieves pain in nerves; but in the bloodstream, it inactivates the blood-clotting cells called platelets. Gene research, however, envisions a better, smarter medicine. If a disease can be linked to a gene, and the gene's protein "product" can be learned, then two possible forms of therapy present themselves. One is to compensate for the malfunctioning protein. The other is to replace the defective gene so that it makes a protein that works. The obstacles involved in either strategy, however, are immediately apparent in the case of Lou Gehrig's disease, an ailment that causes paralysis and death. Scientists at Massachusetts General Hospital and a dozen other institutions announced last week that some people with an inherited form of the ailment (which is also known as amyotrophic lateral sclerosis, or ALS), have a gene defect in common. The gene carries instructions for making superoxide dismutase (SOD), a protein that acts as a kind of housecleaner inside virtually all cells. ALS patients, however, have a problem only in a very specific group of cells - the ones in the brain and spinal cord that "drive" muscles. Assuming the root problem is not enough SOD - and this isn't known for sure - giving the patient doses of the protein, or something similar to it, is an obvious strategy. Certain common vitamins behave like SOD, and they will almost certainly be tried first, although anecdotal evidence suggests minimal effects. If SOD is given orally, it will be distributed thoughout the body, risking side effects. Even if there turn out to be no serious ones, this route is unlikely to work because, being a protein, SOD probably will be digested in the stomach and intestines. Injecting it directly into the bloodstream is more reliable, but even then it is far from where it needs to be. Obstacles to Quick Fixes The brain and spinal cord are heavily fortified organs, sealed off from the rest of the body by a tight network of cells that form the so-called blood-brain barrier and further protected by cellular pumps actively removing foreign substances that may have leaked in. Getting an intact molecule of SOD through this barricade will not be easy, and may not be possible. Assuming it is, however, the protein must then get through the membrane of the nerve cell - a difficult task that usually requires a "carrier" molecule, which, of course, may not exist for SOD. A way of avoiding the problems of the blood-brain barrier is to have muscle tissue hand off SOD to the nerve fibers attached to it. The protein might then travel up the fiber to the body of the nerve cell through a well-known process called "retrograde transport." But how does one get extra SOD into a muscle cell? A more definitive treatment would be to get a corrected copy of the SOD gene into the nerve cells before they die. A way to do this would be to put the gene into a virus and send the virus in to "infect" the ailing cell. As it happens, polio virus has the ability to target, at least in the spinal cord, exactly the cells that are diseased in ALS. But if polio virus were to function as a Trojan Horse in this way, it would have to be a form of the virus that would cause no other damage. And even then, there's the job of getting the virus into the spinal cord in controlled amounts. For other diseases, the engineering problems may not be so great. In a two-year-old experiment at the National Institutes of Health, two girls with a rare immune system disease have had a crucial enzyme gene put into cells that can be removed from the blood - and returned - with relative ease. In an experiment slated to begin this spring, other NIH researchers hope to treat cystic fibrosis patients by having them inhale viruses carrying a gene now missing in the cells lining their lungs. As medical scientists try to use the new world of genetic knowledge, treatment strategies will have to be "tailored" to fit the personality and behavior of each diseased gene. At this point, no one is willing to say that in many cases the tailor may never be able to make a suit that fits. But it's already clear the treatments are not going to be easy to stitch together, and they're not going to come off the rack. (4) ===== RE: National Library of Medicine ========== Date : Fri, 5 Mar 1993 16:10:00 EST Sender : Medical Libraries Discussion List From : Lori_Klein@OCCSHOST.NLM.NIH.GOV Subject: Expanded Reference service from the NLM The National Library of Medicine (NLM) is expanding its Reference services to handle your requests. Now if telephoning is not convenient and the mail is too slow, you may send your inquiry electronically to REF@NLM.NIH.GOV over the INTERNET. This address has been created to receive and respond to specific reference inquiries from librarians and health professionals; it is not meant for discussions, opinions, or announcements. Messages will be picked up daily (Monday through Friday except for federal holidays), and usually responded to the same or next day. Please be sure to include your BITNET or INTERNET address so that reference staff can respond to you. Inquiries regarding the loan of materials from NLM should still be sent to the Collection Access Section (ILL@NLM.NIH.GOV). Questions about Grateful Med GMHELP@GMEDSERV.NLM.NIH.GOV, and other inquiries regarding the MEDLARS (MEDLARS@NLM.NIH.GOV) of the Library. Lori Klein, Supervisor, Correspondence Unit Reference Section, NLM (301) 496-6097 or klein@lhc.nlm.nih.gov == end of als 28 ==