Date: Wed, 9 Aug 95 11:24:37 -0400 From: Bob Broedel To: als@huey.met.fsu.edu Subject: ALSD207 ALS-ON-LINE =============================================================== == == == ----------- ALS Interest Group ----------- == == ALS Digest (#207, 09 August 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 == == 850+ 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 .. Editorial 2 .. MDA Research Report #58 3 .. ALS in the USA 4 .. ALS in the United States - correction 5 .. re: diet & ALS (1) ===== Editorial ========== Starting tomorrow, I will be out of town for ten days. Issue 208 won't be published till I get back to Tallahassee. Remember please, this editor is not a medical doctor, a lawyer, etc. and this is not a peer-reviewed publication. rgds,bro (2) ===== MDA Research Report #58 ========== Date : 08 Aug 95 22:43:51 EDT >From : Barry Goldberg <71154.330@compuserve.com> Subject: MDA Research Report #58 Below is the latest Research Report to be issued from MDA to its clinic directors. Please note that each abstract is followed by the complete report reference. I hope you find this information useful. MDA STAFF RESEARCH UPDATE -- SRU #58 -- 07/31/95 ************************************************ MYOTONIC DYSTROPHY (DM) is associated with a defect in a gene that codes for a protein kinase, sometimes abbreviated DMK. The exact role of this protein in the body is still unknown and MDA scientists have developed antibodies to DMK in order to tag the DMK protein in tissues throughout the body. By tagging the protein researchers can determine where DMK is located and theorize what its function(s) might be. Recent results provide evidence that the DMK protein may exist in a couple of different forms as two different sized proteins have been detected. DMK has been found at the neuromuscular junction in skeletal muscle and in certain areas in cardiac muscle as well as in different specialized regions of the brain. The locations suggest that DMK may have a role in cell-to-cell communication such as sending signals between nerve and muscle. Although the locations found for DMK correspond to areas that exhibit clinical signs of DM, further characterization of the protein is necessary to more fully understand its role and how the defect in DM leads to the development of the disease. (Whiting, E.J. et al. Human Molecular Genetics 1995; 4:1063- 1072). A characteristic type of cataract can be observed in individuals with MYOTONIC DYSTROPHY (DM). Cataract screening was recently tested to determine how effective such a screen might be as a first step in the diagnosis of the disorder. Generally, few people are initially diagnosed with DM using eye examines although it is part of a diagnostic work-up for the disease. The research study included individuals with cataracts who had other signs of DM as well as individuals with no signs of DM who had cataracts and were under 60 years of age, since cataracts are common in the elderly. Through the screening, cases of DM were diagnosed and the results showed that there is a relatively high frequency of undiagnosed DM in individuals with cataracts in the age group studied. The researchers concluded that selective screening of individuals with cataracts would be productive, and proposed that screening be considered for individuals under age 55 who have cataracts in both eyes and individuals of any age who have cataracts with certain DM-like features. (Kidd, A. et al. Journal of Medical Genetics 1995; 32:519-523). SPINAL MUSCULAR DYSTROPHY (SMA) is characterized by deletions and rearrangements of DNA in the area containing the gene or genes that are affected in this inherited disorder. These features indicate that the DNA in the SMA region is unstable and an MDA-supported research group recently identified a specific element that may be responsible for the instability. The element is called THE-1 and it exists in about 10,000 places in the human genome -- genome refers to the entire collection of genes in an organism. THE-1 has previously been found associated with areas in the genome that are unstable and the scientists believe that THE-1 may be promoting the existence of deletions and duplications in the highly variable region that contains the SMA disease gene(s). (Francis, M.J. et al. Genomics 1995; 27:366- 369). A debate continues to exist as to whether primary lateral sclerosis (PLS) is distinct from AMYOTROPHIC LATERAL SCLEROSIS (ALS). The criteria for diagnosis of ALS includes both upper and lower motor neuron signs with both inherited and noninherited forms of the disorder. PLS is not inherited and is described as showing progressive upper motor neuron loss with no damage to the lower motor neurons. The average survival for individuals with PLS is generally 4 to 5 times that for ALS. A research group based in The Netherlands recently described three individuals who were diagnosed with PLS and who eventually developed ALS after 7.5 to 27 years. They conclude that although PLS and the non-inherited version of ALS may be different forms of the same disorder, maintaining a differential diagnosis for PLS may be justified due to the difference in prognosis between the disorders. (Bruyn, R.P.M. et al. Journal of Neurology, Neurosurgery & Psychiatry 1995; 58:742-744). Glutamate transport has been shown to be abnormal in AMYOTROPHIC LATERAL SCLEROSIS (ALS). Glutamate is a naturally existing factor involved in the transmission of signals in the nervous system, however, glutamate is damaging to neurons if it accumulates and is not transported away from the neurons during the signaling process. Researchers are looking for what may be hampering the transportation of glutamate in ALS and they recently examined three different glutamate transporters. Two exist in a type of cell in the nervous system that functions to support the neurons -- glial cells -- and one transporter is found in neurons themselves. GLT-1 is a glutamate transporter found in certain glial cells and MDA-supported scientists determined that the amount of GLT-1 is significantly reduced in nervous tissue that is affected in ALS, however, there is no apparent destruction of the glial cells. The researchers conclude that GLT-1 is selectively lost in ALS and this may contribute to motor neuron destruction, although they have yet to determine if it is a primary or secondary effect in the disorder. (Rothstein, J.D. et al. Annals of Neurology 1995; 38: 73-84). MYASTHENIA GRAVIS (MG) is an autoimmune disease and is usually not inherited although families with more than one affected individual can be found. In these families the same form of MG is apparently affecting different family members. However, a recent study of four Italian families revealed that different forms of the disease can be present within one family. Previous findings of familial occurrence of MG and the current observation that different forms of MG can exist in one family, considered together, indicate that familial MG is not specifically linked to a particular feature of the immune system. The researchers propose that a general susceptibility to autoimmune diseases may be the common link between family members. (Evoli, A., et al. Journal of Neurology, Neurosurgery & Psychiatry 1995; 58:729- 731). LAMBERT-EATON MYASTHENIA SYNDROME (LEMS) is a disorder affecting the neuromuscular junction and is generally associated with small-cell lung carcinoma. A recent study supports the observation that LEMS may also be associated with other tumors or abnormal tissue growth. Some individuals have been found to be affected by both LEMS and lymphoproliferative disease involving certain forms of sarcoma, leukemia or lymphoma. The clinicians suggest that individuals with lymphoproliferative disease who also exhibit unexplained muscle weakness should be evaluated for LEMS since these diseases appear to be another risk factor for LEMS. (Argov, Z. et al. Muscle and Nerve 1995; 18:715-719). Inclusion body myositis (IBM), POLYMYOSITIS and DERMATOMYOSITIS (PM/DM) are all classified as inflammatory myopathies. Prednisone therapy was evaluated as a possible treatment for IBM, however, during administration of the immunosuppressive medication to individuals with the disorder muscle strength continued to decrease. Therefore, the inflammatory response in IBM muscle is not the only factor involved in the course of the disease. The investigators previously showed that another immunosuppressive therapy -- intravenous immunoglobulin or IVIg -- was also ineffective in IBM, but IVIg apparently does provide benefit for dermatomyositis. The clinical researchers conclude that the progression of IBM cannot be explained by the inflammation observed in the muscle and additional work is necessary to determine exactly how the disease develops. (Barohn, R.J. et al. Neurology 1995; 45:1302-1304). MITOCHONDRIAL MYOPATHIES (MITO), which result in muscle weakness due to metabolic problems, are caused by various defects in the function of mitochondria -- the "power plants" for cells. Different types of therapies to enhance the function of mitochondria have provided benefit, however, a general treatment is not yet available. A medication called sodium dichloroacetate (DCA), which has been used successfully to treat one type of metabolic disorder, was recently tested in a double-blind, placebo-controlled trial over a period of one week to determine if DCA's stimulatory activity in mitochondria would be useful for individuals affected by mitochondrial disorders. The analysis of the biochemical effects that were measured in the trial demonstrated that DCA could be beneficial for individuals with mitochondrial diseases. Unfortunately, the individuals involved did not report any changes in their symptoms during the study. This could be due to a failure of the measured biochemical changes to provide significant improvement or could be due to the short duration of the study that might not have allowed the individuals involved to experience any benefit. The researchers conclude that short-term treatment with DCA enhanced certain metabolic processes in some of the tissues for a variety of different types of mitochondrial diseases and a variety of mitochondrial disorders may benefit from DCA treatment. (De Stefano, N. et al. Neurology 1995; 45: 1193-1198). McARDLE'S DISEASE (PYGM) is an inherited metabolic disorder in muscle that results from a deficiency in functional muscle glycogen phosphorylase. Two different gene defects have been found and both appear to cause the production of a small, nonfunctional protein that would lead to the inability to use glycogen, an energy source for muscle. In addition, glycogen phosphorylase contains vitamin B6 and researchers in the United Kingdom tested whether individuals with McArdle's disease are affected by what may be a reduced availability of the vitamin. The results of the study show that there was an improvement in force generation and the muscle was less susceptible to fatigue with vitamin B6 supplementation. The researchers suggest that the observed benefits may result in a correction of metabolism of the vitamin or it could compensate for impaired glycogen metabolism. If the latter is true then other metabolic disorders in which glycogen degradation is impaired could benefit from similar supplements. However, anyone wishing to take vitamin supplements should first consult their physician. (Beynon, R.J. et al. Muscle and Nerve 1995; Suppl 3:S18-S22). MYOTUBULAR MYOPATHY is a rare disease affecting males in which it is believed that normal muscle development is arrested. A dozen or so families affected by the disorder have been studied genetically and it was found that the defective gene is located in a certain region on the X chromosome. However, one family recently examined could not be linked to this same area and the researchers suggest that myotubular myopathy may also result from another defect in a different location on the X chromosome. These results are significant for genetic counseling concerning myotubular myopathy. (Samson, F. et al. American Journal of Human Genetics 1995; 57:120-126). cc: "Ray Harwood -- Data Basix: (602)721-1988" [RHarwood@Data.Basix.Com] --- MDA -- Working to find the cure for neuromuscular disease --- (3) ===== ALS in the USA ========== Date : Tue, 08 Aug 1995 15:19:08 >From : Stuart.Neilson@brunel.ac.uk (hssrsdn) Subject: ALS in the USA Dear Mike Bertschy, You recently asked why the USA has 33% of ALS cases amongst 6% of world population. There are several reasonable explanations for this: 1. The data don't reflect disease (as you suggest), especially in countries with high rates of infectious disease which tend to be prioritised. Some countries simply don't report all disease data (eg: AIDS data, even when available, are often "sanitised"), and a few of these countries have vast populations. The world count that you have is therefore likely to be an under-estimate. 2. The proprtion of elderly people in the States (25% over 65) is much higher than in the world population (3% over 65). More than 60% of ALS cases in the US are aged over 65. About half of the population of Africa is aged under twenty years, and ALS is exceptionally rare in the first two decades of life. The national age structure is the greatest factor affecting the apparent prevalence - you should use "standardised incidence ratios" or "age-adjusted rates" when comparing populations with different age compositions. 3. ALS as a cause of illness and death "competes" with other diseases. As general mortality falls, ALS (and other neurological conditions) become more frequent than might be expected from the change in age composition alone due to the greater chance that susceptible individuals will live to ages at which these conditions are detectable. Therefore even age-adjusted rates will vary between countries - however age-adjusted rates of ALS mortality correlate highly with national life-expectancy both within individual countries over time and between countries (see eg: Neilson et al, "Rising mortality from motor neurone disease: An explanation", Acta Neurologica Scandinavica 1993;87(3):184-191). Please let me know where you found data on the number of reported cases of ALS diagnosis as it would be most useful to have the reference. Dr Stuart Neilson CSHSD, Brunel University. WWW: http://http1.brunel.ac.uk:8080/~hssrsdn/ (4) ===== ALS in the United States - correction ========== Date : Wed, 09 Aug 1995 09:49:42 >From : Stuart.Neilson@brunel.ac.uk (hssrsdn) Subject: ALS in the United States - correction My apologies for a glaring error! About 11% of the US population is aged 65 years or older, not 25% as I stated. The equivalent figures are 15% in the UK and 17% in Sweden. The rest of the figures are okay. Stuart. (5) ===== re: diet & ALS ========== Date: Wed, 9 Aug 1995 00:08:00 -0400 >From : DENFIN@aol.com To : broedel@geomag.gly.fsu.edu Cc : hfryauf@blue.weeg.uiowa.edu, JanF@aol.com, : 76001.3670@compuserve.com, TTorgerson@aol.com Subject: Re: ALSD206 ALS-ON-LINE In a message dated 95-08-08 02:45:39 EDT, you write: > >Why does the U.S. have roughly 33% (23,000 / 70,000) of all reported cases >of ALS when it only has 6% (250 mil / 4.5 bil) of the world's population? >I understand that "reported" is a key word, but does it explain the 27% >difference? > >Thanks, Mike Bertschy > Dear Bob, (info Mike, Joel, Jan, etc.) You have not published material on nutrition that I have sent you which would help to answer the above question. I have other material that would help answer other questions like the one on a Macrobiotic Diet but am reluctant to go to the effort to send it. Did you receive my information? How do you decide what gets distributed? I am not a vitamin pusher, I am a biochemist who is convinced that the answer to the above question is our lousy diets and our toxins. A Macrobiotic diet is a healthy diet and a much better diet to be on for most people than a celery and water diet which seems dangerous. Andrew Weil lists celery with peanuts as a food to minimze intake of due to naturally occuring toxins. People with any disease should read about the magnesium, omega 3 oil, and other deficiencies, and minimize toxin intake by minimizing saturated fat and the harmful trans fats that are in so many of our processed foods. Pure water is essential and alcohol intake as per Tom's question, should be minimized. These factors are contributing to many epidemics and too many people want to write supplemental nutrition off as hype just because there are SOME exagarated claims made for SOME nutrients. Please let me know if you received my material and what your criteria are for including information. Greenlanders don't get any breast cancer, MS, diabetes, asthma, etc., and they get much less of other major diseases (their population may not be large enough for statistically significant information on ALS) and it is looking more and more like the higher intake of omega 3 and monounsaturated oil & magnesium are major factors in this difference. Most people don't realize how very important nutrition is in avoiding disease and almost everyone needs extra C, E, Mg, omega 3 oil as described in my e-text. Please help me help educate your readers on the importance of good nutrition. I do not sell any of this material. I am selling my e-text at cost so I can continue what looks to me like very important work. Here is some of the info that I have compiled in an e-text that I hope to have on the web soon and is available by snail mail (at cost) now: I can provide as much info as you will publish, but 20 pages would provide the info most applicable to ALS. If any of the info addresses try my suggestions, please let me know the results. _______________________________________________________________ ALS (Amyotrophic Lateral Sclerosis) ALS is also known as Lou Gherig's disease. A 12 January 1994 article in BIO/Technology (Vol 12), "As We Live And Breathe: Free Radicals and Aging," by Stephen Edgington describes the linkage of 11 point mutations in families predisposed to ALS with the copper/zinc superoxide dismutase gene (SOD1). Robert Brown (Massachusetts General Hospital, Charleston, MA) headed up the team doing the research and stated, "There were over 3000 papers in the literature on ALS, while few papers raised the question of free radicals, quite frankly, it was not an area that had been investigated at all." Since familial ALS is a neurodegenerative disease that usually affects individuals later in life and many researchers consider it to be an excellent model for studying the aging process, if I knew anyone suffering from ALS or had an e-mail address for Stephen Hawking, I would certainly recommend they consider the lifestyle described herein as well as lots of the better antioxidants discussed herein, including the MAK recommended by Hari Sharma, M.D., as discussed under FREE RADICALS. You never know, the human body has been shown to have amazing recuperative powers if you treat it optimally! Here is some Internet e-mail on the subject of ALS from Frances Frech, Director, Population Renewal Office: We have been interested in ALS (Lou Gehrig's Disease) for quite some time after learning that ALS sufferers, like Alzheimer's victims, have aluminum in their brain cells. We had read that the highest rate of both ALS and AD are in Guam, where there's a larger-than-usual amount of aluminum in the water. It's also 100% fluoridated, which is another key factor. The same as in AD, researchers refuse to see the significance of the aluminum deposits. There is a drug, deferroxamine (DFO) which a Canadian medical scientist, Donald MacLachlan has been using to remove aluminum from AD victims. But he doesn't see it as a cure because further intake of aluminum has to be stopped, and he doesn't know where it's coming from. To the best of our knowledge, DFO hasn't been tried in ALS, but it could be if one could find a doctor who is willing to try it. (it's an approved drug, originally designed to remove iron from victims of iron overload disease, but it was found to be able also to remove aluminum.) But halting aluminum intake is also crucial, and should be done, in any case. However, it's extremely difficult. All city water is treated with aluminum sulfate to settle solid wastes. Ordinarily, that poses no problem, for it settles along with the waste and very little shows up in the tap water --except when it's fluoridated. Then a lot of it will, in the form of aluminum fluoride. (This is from the Journal of Environmental Engineering, Feb.-Mar., 1984.) ALS and AD victims could--and should--use water purified by distillation or reverse osmosis--for drinking, cooking, and reconstituting juices made from concentrates. The hard part is avoiding foods and drinks processed with fluoridated city water, and nowadays most of it is--62 1/2% so far, and soon to be more, with California, one of the least fluoridated states, having just passed a mandatory fluoridation law. We are curious because of something we've observed: All the people we've known or known of who have ALS tend to be light-skinned, blonde or red-headed, blue-eyed, and of Northern European ancestry. (Even in Guam large numbers of the population are mixed blood descendants of Danish explorers and sailors.) The skin, hair, and eye color have something to do with having less melanin, and we think this could be an important clue. But we haven't pursued the whole story yet. First we're trying to learn if we're on the right track concerning the ancestry of ALS victims. ____________________________________________________________________ Sincerely, Dennis Fink Biochemist === end of als 207 ===