Date: Thu, 20 Apr 95 02:09:03 -0400 From: Bob Broedel To: als@huey.met.fsu.edu Subject: ALSD186 ALS-ON-LINE =============================================================== == == == ----------- ALS Interest Group ----------- == == ALS Digest (#186, 19 April 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 == == 650+ 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 .. some questions 2 .. something to begin 3 .. C-3036 4 .. Searching for a relative with ALS 5 .. presentation by Dr. Zach Hall of NINDS (1) ===== some questions ========== >From : Tony McDonough Date : Wed, 19 Apr 95 18:45:43 BST Subject: Some questions Hi Bob, thank you for your efforts on our newsletter. It really is appreciated here in the UK. I saw some time ago there will be a board of eminent researchers who will be answering questions from patients on April 30th somewhere in the US. I was wondering if anyone who subscribes to our group is going along, and if so I have some questions I would like to ask. Also is it possible we can have a transcript of this meeting in a seperate bulletin? My questions are: In the view of the panel, 1. How significant are the recent results which were announced for Riluzole? 2. What progress has there been recently with genetic research for sporadic ALS? 3. Are we any closer to understanding how the disease progresses? 4. Is it possible ALS is a muscle cell disease rather than nerve cell? 5. Is it likely we will be able to regenerate nerve and muscle cells in the foreseeable future. Can the panel expand on this area? 6. What hope is there for existing patients? Regards Tony (2) ===== something to begin ========== Date : Thu, 13 Apr 1995 16:12:01 -0400 >From : vblok@mars.superlink.net (Dr. Victor R. Blok) To : als-talk@mailer.fsu.edu Subject: something to begin Dear Netters, I asked this questions on ALS digest group, but I am not sure was it published or not. Any case I think that any question concerning safety or mechanism of action of Riluzole would be very important to discuss. An interest recently arose to Riluzole, and I have several questions in connection with it . The chemical structure of Riluzole suggests that it must not dissolve well in neutral cold water, but must easily dissolve in water with addition of acids, e.g. in stomach, and must not dissolve at all and consequently may sedimentate in alkaline media of intestine, which may cause ulceration. If for example a patient has gg-tube and thus Riluzole goes directly into intestine, sedimentation scenario doesn't look improbable. Is it possible that some of the side effects like nausea may be attributed to this kind of dissolution problem ? Other questions concern an early trial of Riluzole for schizophrenia patients . Does Riluzole have any sedative action , does it cross blood-brain barrier? And finally, I haven't seen any proof that Riluzole actually slows release of Glutamate into intercellular space, as it was reasonably but purely theoretically suggested. Is there any experimental evidence for that ? It may be done on mice, and this measurement may give immediately some estimate for the minimal active dose, say 20 mkg/kg, instead of presently accepted, God knows on what basis, 50 - 200 mg/day independently on weight. Sincerely, Victor Blok. (3) ===== C-3036 ========== Date : Fri, 14 Apr 1995 14:57:32 -0700 >From : zantron@ix.netcom.com (Anthony R. Zangara) Subject: ALS Digest At present I subscribe to The PLS Newsletter, which is published Frank Levy, Ph.D. (Chemistry), Editor, E-Mail 73112.611@compuserve.com. The Assistant Editor is Mimshen Comstock, MA 8511 NW 5th Street, Pembroke Pines, Fl. 33024. To Subscribe the cost is $10.00/year. Frank has been on a treatment for three years with a formula C-3036, and he has experienced a minimal progression of his PLS condition since he has been taking it. He takes it three times daily and as a result he is still not wheelchair bound, and his condition affects only his lower body. He has kept a daily diary of his PLS progression, I believe since the time of it's onset. He also mentions in his newsletter there about 15 people presently using C-3036, with good effect, namely stopping the worsening of the symptoms. It does not, however improve them, therefore it is difficult to determine if it is effective. That is why, it paramount to keep good records. Dr. Levy has an L-values chart (graph) he developed for record keeping, that he offers to ALS/PLS people on request. He has kept a record of his condition for three years prior toand three years after the use of the C-3036. C-3036, from what I gather, is the product of a Dr. Helmut Prahl. For anyone interested in the program they should contact Dr. Frank Levy, Ph.D. at 101 Pinta Court, Los Gatos, Ca. 95032 or the noted E-Mail address noted above. I am presently trying to get into the C-3036 program, with the concurrance of my neurologist. I will keep you informed. Tony Zangara (4) ===== Searching for a relative with ALS ========== Date : Tue, 18 Apr 1995 11:29:25 -0700 >From : chris@skoo.com (Chris Hammond) Subject: Searching for a relative with ALS Cliff Hammond, living with ALS since 91 or 92, has recently learned of a relative said to have ALS. This relative (name unknown) is the son of Howard and Margaret Hammond, Margaret is assumed to be residing in Walla Walla Washington. We want to confirm if this relative does have ALS, and if so, compare symptoms, etc. Please contact us if you have any information at: chris@skoo.com Thank you, Family of Cliff Hammond ----------------------------- Chris Hammond Animation chris@skoo.com http://www.skoo.com/~chris/ (5) ===== presentation by Dr. Zach Hall of NINDS ========== HOUSE APPROPRIATIONS LABOR, HEALTH AND HUMAN SERVICES, AND EDUCATION SUBCOMMITTEE MARCH 23, 1995 COPYRIGHT IS NOT CLAIMED AS TO ANY PART OF THE ORIGINAL WORK PREPARED BY A UNITED STATES GOVERNMENT OFFICER OR EMPLOYEE AS A PART OF THAT PERSON'S OFFICIAL DUTIES. ------------------------ Mr. Chairman and Committee Members: As the new Director of the National Institute of Neurological Disorders and Stroke, I am pleased to appear before the Committee for the first time. I have come to the National Institutes of Health (NIH) from the University of California where I had almost twenty years of experience as a laboratory researcher and grantee of NIH, as a mentor to young scientists, and as an administrative leader of biomedical research. I came to the NIH because this is a moment in our history of exceptional promise for research on disorders of the brain, and because NIH is the world-wide leader in performing and sponsoring that research. In my new position as Director of this Institute, I look forward to working with you, with the neurological research community, with patient organizations, and with the public toward our common goal of advancing knowledge that will improve the prevention, diagnosis and treatment of diseases of the brain, spinal cord, and peripheral nerves. Disorders of the nervous system are among the most common and debilitating in our society. Stroke, epilepsy, Alzheimer's disease, multiple sclerosis, cerebral palsy, Amyotrophic Lateral Sclerosis (ALS) or Lou Gehrig's disease, brain tumors, and traumatic injury of the brain or spinal cord--most of us have family or friends with one of these disorders--someone who has difficulty with memory, with movement or with communication. Because the brain is so complex and because it has limited ability to repair itself, these diseases are among the most intractable that afflict mankind. Thus, patients with neurological disorders often live for many years with severe disabilities, resulting in special personal and financial burdens for their families and for society. The treatment of neurological diseases, however, is on the verge of fundamental change. Dramatic and continuing advances in our understanding of the brain are paving the way toward the development of new treatments that will offer hope to millions of Americans. I believe that we are on the threshold of an era in which successful treatment of brain disorders will become commonplace rather than the exception. Today I will highlight recent advances in three areas and indicate their future promise. The first is in the direct testing of medications and procedures that help people avoid, or recover from, brain disorders. Stroke is the third leading cause of death in the American population and the leading cause of disability; each year there are over 500,000 new cases. During the past year, findings from a major clinical trial show that in patients with a partial blockage of an artery that carries blood to the brain, surgery to clear the artery is effective in preventing strokes, even if the patient has no symptoms. Stroke, however, has many causes and no single medication or treatment will be effective for all. One common cause is a heart condition known as atrial fibrillation. NINDS researchers have now found that for most people with this condition, who are under 75 years old, the common drug aspirin provides adequate protection with minimal risk. This finding is important because the alternative to aspirin is a more expensive drug with greater risk for complications. In other ongoing research we are sponsoring a clinical trial to determine whether the hormone estrogen can prevent stroke in post menopausal women. Widespread application of treatments based on all.of these findings has the potential to save thousands of Americans from stroke and disability. NINDS research has also made a difference in the treatment of the youngest Americans affected by brain disorders--very low birthweight infants. These children are usually born prematurely and weigh less than three pounds. Under these conditions the brain is especially at risk for bleeding, which in severe cases can lead to permanent damage. Last year results from a clinical trial demonstrated that a common medication, indomethacin, given 6-12 hours after birth of these infants, dramatically reduced the extent and severity of bleeding, thus reducing the incidence of life-long disability. Very low birthweight babies are also at risk for cerebral palsy. In fact, although they constitute only a small fraction of all births, very low birthweight : infants contribute nearly one-third of all cases of cerebral palsy. An NINDS scientist has recently found evidence suggesting that a very common and inexpensive chemical, magnesium sulfate, given to the mothers of these infants before delivery, can almost completely reduce their risk of cerebral palsy. Modern medical science is often accused of fostering high- technology solutions to health care, and indeed, by its very success, of increasing the cost of medical care. Our ability to improve the survival of those with stroke, with brain or spinal cord injury, or of preterm infants, for example, can be argued to have increased the number of those with expensive disabilities. I would contend, however, that this is to take the short view. In each of the examples described above, stroke and low birthweight infants, a common, simple medication can prevent disease leading to long-lasting disability when applied in situations of risk. As our knowledge increases, we can look forward to more instances in which patients not only survive, but go on to live healthy, independent, and productive lives. Let me now turn to two areas that are not immediately connected to patient care, but offer great promise for future progress. Neurogenetics. As you will hear from my colleague, Dr. Francis Collins of the National Center for Human Genome Research, one of the marvels of our scientific age is the ability to find and identify defective genes that are responsible for particular diseases. Interestingly, a large number of genetic diseases affect the brain or neurotruscular system: Huntington's disease, ALS, neurofibromatosis, spinocerebellar ataxia, familial Alzheimer's disease, muscular dystrophy, some types of epilepsy, to name but a few. In many of these cases, the gene has been identified. Yet finding the gene is only the first step in understanding a disease and devising suitable therapies for it. For example, one of the most exciting recent advances in neurogenetics is the discovery that a similar type of genetic defect, a "trinucleotide repeat," is found in several different neurological diseases--fragile X syndrome, myotonic dystrophy, spinobulbar muscular atrophy, Huntington's disease, and several others. In each case, a tiny portion of genetic material is repeated over and over. In Huntington's disease the pattern is repeated 37-100 times, compared to 6-34 times in those who are unaffected. Why this expanded repeat causes disease is completely unknown; the effect appears to be a subtle one, as in several of these cases the diseased gene is "dominant" over the normal gene. As you can see from this example, even when a defective gene is discovered, much remains to be done to understand how the defect leads to disease. This work is important because gene replacement therapy will not be effective or feasible in many cases. What is needed are therapeutic agents that can intervene in the processes that have gone awry because of the defective gene. One of the powerful ways in which molecular genetics can be used is to create animal models of disease in which to study the pathological process and agents that may modify it. For example, NINDS-supported scientists found in 1993 that a gene responsible for many cases of ALS encodes an enzyme that removes the deleterious by-products of cellular metabolism. This discovery has now led to the production of a mouse that has the same enzyme mutation as is found in the human disease. Agents that can protect against these harmful by-products can now be tested in the mouse model of the disease. Among the agents that can be tested are powerful growth factors recently discovered by researchers. Growth factors have recently been found that appear to protect neurons that degenerate in Parkinson's disease and protect from injury the specific neurons afflicted in ALS--the neurons that control our muscles. One example in which enzyme replacement therapy has been successful is Gaucher's disease, a genetic disease affecting young children. In this disease, an enzyme that degrades a special class of fat molecules is missing, leading to lipid accumulation. Several years ago NINDS scientists reported success in treating Gaucher's patients by replacing the enzyme. Other scientists are using genetics to attack a different kind of problem, introducing genes or proteins that can be targeted to brain tumors and that will attack them. In all of these cases, a particular problem for the brain is that to introduce large molecules as therapeutic agents it is necessary to breach the cellular wall around the blood vessels--the so-called blood brain barrier that protects the brain. Further research is needed to develop and test the techniques that will allow us to translate advances in genetic knowledge into practical, effective therapies and preventive measures. Life and death of nerve cells. In many brain diseases-- Alzheimer's, Parkinson's, Huntington's, ALS--selected populations of nerve cells die for unknown reasons. In other disorders, cells that are deprived of oxygen die, as in stroke, or damaged cells die, as in traumatic brain or spinal cord injury. In the latter cases, in which large numbers of cells are injured at the same time, we know that the injured and dying cells release chemicals that result in later waves of cell death and injury. Unlike other organs such as the liver, that can regenerate new cells, cell death in the nervous system represents permanent loss, as new nerve cells cannot arise by cell division in the adult. In each of these cases, why do the cells die, and what can we do to prevent this? Recent research tells us that nerve cells are not necessarily just passive victims--in some cases, we know that they can fight back to prevent death, and in others we know that they can activate cellular suicide programs to kill themselves. We also know that external factors, secreted by other cells, can influence whether a cell lives or dies. Thus, to some extent at least, neurons can regulate their survival and that of other neighboring cells. These cellular processes, used by neurons during development and adult life, represent potentially powerful aids to therapy. If we know more about how they work, we could help damaged neurons to help themselves--by therapeutically enhancing their restorative processes and suppressing the processes responsible for death. Thus, one day we hope to be able to delay the progression of stroke or trauma to the nervous system, and to restore the function of nerve cells that have been lost. Much work remains to reach that point, but our progress over the last twenty years has been remarkable and leads us to hope that neurological disease will indeed become the arena for therapy and recovery that we hope for. Mr. Chairman, the FY 1996 budget request for this Institute is $648,255,000. I would be pleased to answer any questions you might have. === end of als 186 ===