=============================================================== == == == ----------- ALS Interest Group ----------- == == ALS Digest #833 (07 April 2001) == == == == ------ 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 == == 4700+ subscribers in 70+ countries. Please be advised, == == the editor is not a medical doctor and the Digest is == == not peer reviewed. This newsletter is not intended to == == provide medical advice on individual health matters. == == Any such advice should be obtained personally from a == == physician. == == To subscribe, to unsubscribe, to contribute notes, == == etc. to ALS Digest, please send e-mail to: == == bro@met.fsu.edu (Bob Broedel) == == == == Bob Broedel; P.O. Box 20049; Tallahassee, FL 32316 USA == =============================================================== == Back issues of the ALS Digest are available on-line at: == == http://www.glnicholas.com/ == == http://www.alslinks.com == == http://www.alssurvivalguide.com == == http://cc4144-a.ensch1.ov.nl.home.com/~digest == == http://health.oldeman.net == =============================================================== CONTENTS OF THIS ISSUE: 1 .. re: gamma globulin 2 .. Creatine monohydrate 3 .. Stem Cells Step Closer to Clinic 4 .. Communication Resource 5 .. Lift For Sale 6 .. Todays Caregiver magazine (1) ===== re: gamma globulin ========== >From : RayAnnRobertson@aol.com Date : Mon, 2 Apr 2001 Subject: ALSD #826-7 Has anyone developed additional information, pro or con, to add to Harry Gould's revealing comments on the new effective treatment for ALS (gamma globulin), as outlined in ALS Digest 826 7 dated 3/29/01. Thank you. Ann Robertson rayannrobertson@aol.com (2) ===== Creatine monohydrate ========== Date : Sun, 01 Apr 2001 Subject: Creatine monohydrate >From : eliork My 11 year old son has SMA 2 which is similar to ALS in more ways than just damage to the Anterior Horn Cells. Can anyone out there answer the following questions: 1) Are there any alternatives to Bi-Pap? What is usually the next support system for breathing when Bi-Pap becomes not enough? 2) Is it accurate to assume from reading research literature that an average adult participant in a Creatine study gets between 1,000 Mg and 1,500 Mg creatine per day and that so far the results are encouraging? 3) Dr. Evan Snyder from Harvard is doing Stem Studies in primates. How do I get my son into the first study on the effect of Stem Cells on humans? Does anyone knows the e-mail of Dr. Snyder? And the last question, 4) Does anyone out there know of any research on ALS, SMA, and DMSO and Microhydrin? Sincerely, Elior Kinarthy, Ph.D. Psychologist (3) ===== Stem Cells Step Closer to Clinic ========== Date : Fri, 6 Apr 2001 >From : Will Hubben Subject: Stem Cells Step Closer to the Clinic - Paralysis Partially : Reversed in Rats With ALS-like Disease from JAMA, April 4, 2001: http://jama.ama-assn.org/issues/current/ffull/jmn0404-1.html Stem Cells Step Closer to the Clinic - Paralysis Partially Reversed in Rats With ALS-like Disease - Brian Vastag Clearly, something is wrong with the white lab rat. Back arched, haunches tensed, he wobbles about the tabletop, hind feet splaying with each step. But what's wrong with him is also what's right. Three months ago, the rat's lower body lay paralyzed due to a nerve- eating virus that mimics neurological disorders like amyotrophic lateral sclerosis (ALS). He scooted around on front legs, dragging his hindquarters like a tiny sled. Now he can walk, albeit clumsily. In the most dramatic demonstration of stem cells' potential to date, this rat and a dozen others partially recovered from paralysis after injections of laboratory-sprouted, intermediate-stage stem cells. Grown from a patch of fetal tissue, these human cells settled into the rat's spinal column and--somehow--brought life to dead feet. "This kind of result is more than we could imagine," said John D. Gearhart, PhD, the Johns Hopkins University stem cell guru whose lab provided the cells for the experiment. As if still reeling from the unexpected, Gearhart motions to the computer monitor displaying the rodent highlight reel and adds, "I really don't know what to tell you." With a scientific article fully describing their results in progress, Gearhart and the man who conceived the experiment, Hopkins neurologist Douglas Kerr, MD, PhD, are tight-lipped about details. But both offer a bevy of cautions. They don't know if the transplants are safe. They don't know when stem cell transplants will be ready for human tests. And they warn that their experimental model applies most readily to ALS, also called Lou Gehrig disease, and related conditions, not to catastrophic spinal injuries. PATCHING INTO THE SPINE As Gearhart and Kerr first reported at the November meeting of the Society for Neuroscience, like a circuit board rerouting itself on the fly, at least a few of the half-million human stem cells delivered to each rat patched into the rodent nervous system. After injection into the cerebrospinal fluid at the base of the spine, the cells floated all the way to the brain stem. "They're just carried by the wind, so to speak," said Kerr. Along the way, some migrated, through a membrane sheathing the spinal column, toward areas of damage. Upon arrival, a few took up residence. In contrast, Kerr said that in paralyzed control animals, which received injections of cells other than viable stem cells, there was no evidence of migration. "It's fascinating, they inject the stem cells in one place and they migrate to the damage," said Lucie Bruijn, PhD, scientific director of the ALS ssociation, who is familiar with the Hopkins work and with other experiments that show that stem cells tend to settle in injured regions of mouse and rat brains. The most notable of these studies was reported from Harvard University and Boston's Children's Hospital. A series of investigations headed by Evan Snyder, MD, PhD, demonstrated that neural stem cells--more mature than embryonic stem cells-- zoom to areas of brain damage caused by tumors and other injuries (Proc Natl Acad Sci. 2000;97:12846-12851). Kerr said that in his experiments, about 6% of the stem cells that reached the interior of the spinal column sprouted into "what appear to be neurons," as confirmed by the presence of surface markers unique to nerve cells. If confirmed, this biological blossoming would offer compelling evidence of stem cells' ability to take cues from their environment. Upon injection, the cells carried the potential to transform not only into nerves, but also into muscle, cartilage, or blood. Something in the environment would have had to trigger their trip down the nerve pathway. The implications astound. Transplanted stem cells may respond to programming within the injured body, learning what to be when they grow up by listening to their neighbors, responding to various broths of growth factors and other signals. Researchers have observed stem cells differentiating into appropriate cell types in the developing brains of rodents, said Ron McKay, PhD, a stem cell expert at the National Institute of Neurological Disorders and Stroke (NINDS), Bethesda, Md. But so far, he said, no one has published research showing a similar process at work in disease models. For the time being, at least, how this cellular drama played out in the paralyzed rats remains speculation. So does the question of how the newly grafted cells contributed to the rats' recovery. "The question now becomes why," said Kerr. "It's a really big why." After the November conference, word of the experiment began to circulate among neurologists and stem cell researchers, said Bruijn. For her, the key question is whether the nerve cells are motor neurons--a special type that controls muscle movement and mysteriously dies in ALS and similar diseases. "The important thing is, if these cells are indeed motor neurons, are they able to reconnect correctly?" A NEUROLOGICAL MODEL Bruijn's question is the billion-dollar challenge. The largest cells in the body, motor neurons control movement with long axons that shoot from the spinal column out to muscle cells. In the Hopkins experiment, Kerr used a virus called Sindbis to destroy these cells. Sindbis virus targets the lower motor neurons, which control movement by sending signals to muscle cells. Upper motor neurons complete a feedback loop, receiving sensory input from the muscles. In ALS, both types of neurons die, leading to paralysis and death. Typically appearing in middle age, the disease affects an estimated 20,000 people in the United States. A small proportion of cases--perhaps 5% to 10%--are inherited, apparently caused by mutations in the gene for superoxide dismutase, an enzyme that scours toxic free radicals. But the etiology of the majority of cases remains unknown. The only treatment approved by the US Food and Drug Administration, a drug called riluzole (Rilutek, Aventis Pasteur, Swiftwater, Pa), extends the life span of ALS patients by a few months. In a similar disease, spinal motor atrophy (SMA), only the lower motor neurons perish. The most common inherited neurological disorder and the most common inherited cause of infant death, SMA kills quickly. About 1 in 40 adults carries genes for the recessive condition, translating to between 1 in 6000 and 1 in 20,000 children being born with SMA. These infants are weak at birth and have trouble swallowing and breathing. Some live to young childhood. Most do not. The Sindbis virus model replicates SMA most faithfully: it too kills off only the muscle-moving lower motor neurons. To help restore movement directly, the stem cells injected into the paralyzed rats would have had to develop into this specialized cell type, growing long axons out to muscle cells and, in Bruijn's words, "connecting correctly." But Kerr believes another possibility exists: "The other explanation is that the stem cells themselves haven't restored movement but that, instead, they protect or stimulate the few undamaged nerve cells that still remain." THE LONG ROAD TO NEURON Whether stem cells can prod damaged tissue to regenerate by providing a nourishing environment is one of the biggest questions in the field. Another is how to steer embryonic stem cells toward various specific cell types. "In some cases, this is being worked out effectively," said Gearhart, who jump-started the field with embryonic stem cells gleaned from fetal tissue (Proc Natl Acad Sci. 1998;95:13726-13731). "But in most cases, no." So Gearhart and his colleagues struck on another approach, which bore first fruit with the paralyzed rats. Why not transplant immature cells, which still harbor the potential to grow and learn? To visualize these cells, imagine that the 200-mile stretch of Interstate 95 from Washington to New York represents the developmental journey from stem cell to neuron. Along the route, there are obvious stops--Baltimore, Philadelphia, Newark--corresponding to well-defined cell types. But there are also intermediate places. The cells used in the Hopkins study came from one of these nether zones, somewhere close to Washington--close to embryonic stem cell, but just nudged up the road toward Baltimore. In contrast, much of the stem cell world is focused on figuring out how to drive stem cells all the way to New York. Insulin-producing pancreatic cells for diabetes, dopamine-making neurons for Parkinson disease, and other specific cell types have obvious applications. The idea has been to transplant mature, functional cells and let them churn out the needed product. And, in fact, there have been recent laboratory successes with this approach. The NINDS team headed by Ron McKay knows a recipe for turning stem cells into dopamine-producing neurons with efficiencies of 50% or better (Nat Biotechnol. 2000;18:675-679). Another group at the University of Wisconsin Medical School in Madison can generate neural stem cells--which can grow into the entire cast of neurons and supporting cells--with 96% efficiency. For diabetes, a team in Spain reversed the disease in rats by transplanting insulin-producing cells descended from embryonic stem cells (Diabetes. 2000;49:157-162). But the disappointment of a recent clinical trial for Parkinson disease opens the door to a different approach, using the more flexible cells. Widely reported in the media, the Parkinson study transplanted mature neurons, recovered from fetuses, into the brains of patients (N Engl J Med. 2001;344:710-719). These cells produced dopamine, the neurotransmitter that wanes with the disease. In some patients, they produced too much dopamine, causing uncontrollable twitching. In others, the neurons did not make enough dopamine to do any good. The study raises questions about whether fully formed neurons can properly integrate into the brain. Curt Freed, MD, lead author on the disappointing study, said that rat experiments show that mature dopamine neurons can grow axons and knit themselves into their environment. But the degree to which they do this remains unknown. The results from the clinical trial suggest that, like tweaking a fussy rheostat, finding the right balance will be tricky. Gearhart thinks there's a better way. "When you're talking about the nervous system, you don't necessarily want a fully differentiated cell going in, because you want to establish cell connections with other neurons. And this kind of connectivity is associated with growth, not with a fully formed cell type," he said. Another stem cell pioneer, James Thomson, PhD, the University of Wisconsin researcher who first described how to culture stem cells obtained from embryos, put it another way. "If you have a more embryonic cell, it might be able to respond to signals better and integrate better," he said. Hence, Gearhart's quest for more versatile cells, first described in January (Proc Natl Acad Sci. 2001;98:113-118). He calls them embryoid body-derived cells, plucked from patchwork balls of embryonic stem cells that have begun growing and differentiating. The new cells still harbor the potential to become all of the tissue types of the body--skin, muscle, bone, nerve. And while they are cultivated from the earliest- stage fetal stem cells, they are easier to grow, reducing the amount of fetal tissue needed for research. In contrast, stem cells derived from embryos are relatively easy to grow. Early indications are that the new cells also reduce the risk of tumors, which runs high with unadulterated embryonic stem cells. Gearhart said his team is working to describe these cells, and so far he and his colleagues have identified 100 subtypes using surface markers and gene expression profiles. He's formed collaborations with research teams to test the cells in rodent models of various diseases. "The important thing, which we've just shown with Doug Kerr and his rats, is that these cells are capable of differentiation," said Gearhart. But how did that biological blossoming restore movement to the mice? "The animals are walking again," said Gearhart. "Now we have to look more closely at the mechanisms. Either way, we can glean something out of this that could have--could have--clinical significance." Stumped About Stem Cells? The term stem cell is used often. But it has many meanings. The following provides a brief guide to these meanings: Embryonic stem cells--Gleaned from days-old embryos or the gonadal ridge of a 5- to 8-week-old aborted fetus, these cells can form every type of tissue except placental. Although these cells were known about for at least 20 years, in 1998 teams at the University of Wisconsin and Johns Hopkins University reported on how to culture the cells, launching a new era of cell engineering. Also called pluripotent stem cells. Adult stem cells--A generic term referring to cells that give rise to specific tissue types, such as blood, muscle, and neural stem cells, found in small numbers in adults. Some research seeks to reprogram these cells, exploring them as possible substitutes for the ethically controversial embryonic stem cells. Neural stem cells--These cells produce all the varieties of neurons and a supporting cast of glial cells. In 1999, scientists at Harvard Medical School found neural stem cells in the brains of adults. Current research seeks to drive neural stem cells toward specific types of neurons to treat disease. Blood stem cells--Found in small numbers in the circulating blood of adults, they generate all the red and white blood cells. The best-studied type of stem cell, they are often infused into cancer patients after chemotherapy to rebuild the immune system. Embryoid body-derived stem cells--Intermediate cells, created in the laboratory by manipulating fetal embryonic stem cells. They show characteristics of neural, blood, and muscle stem cells, among others. First described in early 2001 by Johns Hopkins University scientists. (4) ===== Communication Resource ========== >From : BRomich@aol.com Date : Thu, 5 Apr 2001 Subject: Re: Communication Resource The AAC Institute is a not-for-profit charitable organization dedicated to improved communication for people who rely on augmentative and alternative communication (AAC). Web site: . (5) ===== Lift For Sale ========== Date : Fri, 06 Apr 2001 >From : "M Bazin" Subject: lift For Sale EASY PIVOT :Model EP 85 Like new. (6) ===== Todays Caregiver Magazine ========== Date : Thu, 5 Apr 2001 >From : Gary Barg Subject: Todays Caregiver Magazine Description: Weekly ezine of the first national print magazine for family caregivers. Information includes tips for successful caregiving, legal and financial advice, alternative therapies and nutritional information and celebrity caregiver interviews Subscription Instructions: http://caregiver.com Owner/Host Email Address: gary@caregiver.com === end of alsd 833 ===