=============================================================== == == == ----------- ALS Interest Group ----------- == == ALS Digest (#120, 21 August 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 == == 300+ 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 .. Riluzole 2 .. Intravenis vitamin C and ALS 3 .. Use of Marinol for appetite? 4 .. Inquiry 5 .. Synergen C.N.T.F. Trials 6 .. MDA Research Report #50 7 .. Riluzole Trial Sites (1)=====Riluzole========== Date : Fri, 19 Aug 94 18:02:01 -0400 Sender : fischbeck@a1.mscf.upenn.edu >From : "Dr. Kenneth Fischbeck" Subject: Riluzole Regarding your query of 15 August about riluzole, a study was published in March 1994 in the New England Journal of Medicine by a group from Paris that indicated benefit from riluzole treatment in a subgroup of ALS patients with bulbar onset (difficulty primarily with swallowing & speaking). The study has been criticized on methodological grounds, and should probably be viewed as preliminary at best. U.S. trials are now under way, and should help to determine exactly how effective riluzole is in treating ALS. Contacts for additional information (from previous als@huey messages): Bob Pearson, Public Relations, Rhone-Poulenc Rorer, Collegeville, PA, 800-798-7425 / 610-454-3872; Jim Brown, MDA, Tucson, AZ, 602-529-5317. References: Bensimon G, et al, N Engl J Med 1994;330:585-91; related editorial: 330:636-7; related letters: 331:272-4 (the New England Journal of Medicine is carried by most hospital and medical libraries). Hope this helps. K. Fischbeck, M.D. Neurology Dept., Univ. Pennsylvania Philadelphia, PA 19104 (fischbeck@a1.mscf.upenn.edu) (2)=====Intravenis vitamin C and ALS========== Date : Fri, 19 Aug 94 14:34:06 EST >From : "Mike Doliton" Subject: Intravenis vitamin C and ALS To All, Has anyone heard of 20,000 units of vitamin C being infused into the body intravenously? I listen to the Gary Null Show at noon on WBAI in New York and a Doctor was on describing how vitamin C could help many illnesses like asthma by ridding the body of toxins. He cautioned the audience that a gallon or 2 of water needed to be drunk per day to keep the kidneys flushed out. Has anyone heard of this treatment being done on ALS patients? I'm still alive and kicking only I haven't had much to say for a while. Regards, Michael Doliton Sony Medical Systems (3)=====Use of Marinol for appetite?========== Date : Thu, 18 Aug 1994 14:55:02 -0800 >From : tree@bedford.symantec.com (Tom Emerson) Subject: Use of Marinol for appetite? Greetings all, My father's neurologist prescribed Marinol as an appetite stimulant a few weeks ago, and for the most part it has neither made him hungry (or high, though I don't think the pills contain the right stuff for that ;-) (for those who don't know, Marinol is derived from Marijuana), and we were wondering whether anyone has experience taking or prescribing it and if so, would they pass that information back to me. On an interesting note, Marinol costs ~US$315 for 50 pills. That is a lot of dime bags. Thanks in advance for your help, -tre --- Tom Emerson Software Engineer Development Tools Group Symantec Corporation tree@bedford.symantec.com "I dreamed I had to take a test, in a Dairy Queen, on another planet." (4)=====Inquiry========== Date: 19 Aug 94 13:11:19 EDT >From: "Gordon R. Pounds" <74652.3605@compuserve.com> Subject: Inquiry Please send me any information ALS. Any E mail addresses that you might have of other people with ALS. I am on CompuServe but I can send messages to INTERNET and other services. Thanks for your help. Gordon. PS I have ALS with bulbar involvement primarly. I am interested talking with other patients with bulbar involvement. I have been on a drug study for the last year at Iowa City. My limbs are still fine. My speech and swallowing are gone. (5)=====Synergen C.N.T.F. Trials ========== Date : 20-Aug-94 11:13 EDT >From: Grant L. Nicholas ( 74000.1616@compuserve.com ) Subj : Synergen C.N.T.F. Trials I've tried to keep everyone aware of what has been happening with Dad as regards the C.N.T.F. trial he was (is) in. He participated in the first six-month trial, and displayed the classic symptoms described as being from C.N.T.F., in that he had the flu every day, about three to four hours after the injection was given. These symptoms, in the severity observed, lead us to believe that Dad was receiving Synergen's largest dose of the drug. The revelations of late regarding dosages given in the two competing trials, are that Synergen's largest dose was smaller than the smallest received in the Regeneron trial. During the time Dad received the injections, there was no dramatic loss in his mobility or observable strength, in fact it seemed that the progression of the disease had halted. Once we figured a way around the flu symptoms that were ruining his day, life was almost routine. We did this by shifting the shot time to the evening, about two hours before bed-time, Dad then slept through the flu. Synergen stopped the injections for "one month", over two months ago. This was a planned (one month) break in the test, with a second step scheduled to follow. Dad's lower body strength has taken a decided turn for the worst during this time. He now has trouble standing, and is walking with a walker now. His arms have lost strength as well. While we believe the injections slowed the progress of ALS, we were beginning to loose hope that anything positive would come from the C.N.T.F. trails. In spite of all the negative news lately about both Regeneron and Synergen C.N.T.F. trials, Mom and Dad were notified late yesterday that his new shipment of trial vials has arrived and that Dad has an appointment on August 31 to restart his injection regimen. This stage is to last nine months. We have yet to see the contract that will be negotiated (they state, we sign) for this next step, but at least the road block to further trial injections seems to have been over come. I'll share more as we gain knowledge of the plan for the program. Regards, Grant (6)=====MDA Research Report #50========== Date : 17 Aug 94 15:33:19 EDT >From : Barry Goldberg <71154.330@compuserve.com> Subject: MDA Research Report #50 -- part 1 This message was originally addressed to MD Forum [MD-LIST@DATA.BASIX.COM] and a carbon copy was sent to you. ---------------------------------------- Here's part one of MDA Research Report #50 -- July 29, 1994 TO: MDA Clinic Directors FROM: Norine Stirpe, Ph.D. Director of Research Development RE: Research Update #50 A few familial forms of amyotrophic lateral sclerosis (ALS) have been described by MDA researchers and the disorders are referred to as ALS1, ALS2 and ALS3. The cause of ALS1 has already been found to be a defective SOD1 gene located on chromosome 21. ALS1 and ALS3 are autosomal dominant -- they arise when only one defective gene is inherited from a parent. Clinically these forms of familial ALS cannot be distinguished from the sporadic (noninherited) form of ALS. However, ALS2 is autosomal recessive -- a defective gene from each parent must be inherited in order for the child to have the disease -- and this form of ALS has an early onset and slower progression of symptoms. MDA-supported research has revealed that the defective gene for ALS2 is located in a specific region on chromosome 2. Identifying the defective gene that results in ALS2 will improve understanding of the possible causes of all forms of ALS. (Hentati, A. et al. Nature Genetics 1994; 7:425-428). MDA researchers have identified a gene defect that results in hypokalemic periodic paralysis (HYPoP). The gene contains the information for making what is called the DHP receptor. The receptor participates in the control of the passage of calcium and in the process whereby a muscle is stimulated to contract. Whether one or both of these functions are affected by the gene defect is unknown at this time. Molecular-based diagnosis is now possible for some individuals with HYPoP and further investigations are expected to lead to the identification of additional gene defects for the DHP receptor of others affected by the disease. (Ptcek, L.J. et al. Cell 1994; 77:863-868). Myotonic dystrophy (DM) is known to show its effects in systems in the body other than muscle. Researchers from The Netherlands evaluated whether central nervous system problems could be involved in causing sleepiness in several men and women with DM. They found that the excessive daytime sleepiness of these individuals was a result of abnormalities in breathing during sleep at night. Treatment of some of the individuals with the stimulant methylphenidate provided benefit. (van der Mech, F.G.A. et al. Journal of Neurology, Neurosurgery, and Psychiatry 1994; 57:626-628). Case studies concerning diagnosis of myotonic dystrophy (DM) were recently described which emphasize possible difficulties in relying solely on clinical evaluation to diagnose the disease. Direct DNA analysis is now being used to verify clinical diagnosis of DM. The detection of the DM gene defect is possible in a vast majority of cases, and genetic screening can be especially helpful for asymptomatic individuals or carriers who are at risk from heart problems. (Barnes, P.R.J. et al. Journal Neurology, Neurosurgery, and Psychiatry 1994; 57:662). However, it is important to keep in mind that the expanded segment of the DM gene associated with the disease is not stable. The size of the expansion can vary between individuals in a family and also can vary between different tissues in the body of one individual. Congenital myotonic dystrophy (CDM), the most severe form of myotonic dystrophy, appeared to arise only when the defective myotonic dystrophy gene was inherited from the mother. However, recently reported cases reveal that CDM can be passed on through the father. These observations are significant for genetic counseling and for understanding the basis of the disease. The severity of myotonic dystrophy is directly proportional to the size of the myotonic dystrophy gene defect, which is a larger than normal repeated segment in the gene. The question still exists whether the severe congenital form of myotonic dystrophy is a result of a very large expanded myotonic dystrophy gene segment or whether there is another factor besides the size of the myotonic dystrophy repeat that plays a part in determining if an individual will have CDM. (Nakagawa, M. et al. Journal of Medical Genetics 1994; 31:397-400). Date : 17 Aug 94 14:13:16 EDT >From : Barry Goldberg <71154.330@compuserve.com> Subject: MDA Research Report #50 -- part 2 And here's the remainder of report #50 -- Paramyotonia congenita (PC) is an inherited disorder that generally results in muscle stiffness after exposure to cold, and some individuals experience muscle weakness. Different specific defects in the sodium channel gene have been associated with the disease. How these abnormalities compromise the ability of the channel to function properly is not fully understood. However, the goal of researchers is to find medications that will help overcome the specific defects identified. One gene defect in an individual who did not experience muscle weakness upon exposure to cold was believed to result in a channel with an altered ability to control the flow of sodium. A medication called mexiletine, which inhibits the flow of sodium into the cell, was found to improve the individual's condition. The researchers conclude that the drug was able to overcome the sodium channel abnormalities. (Jackson, C.E. et al. Muscle & Nerve 1994; 17:763-768). Myasthenia gravis results when the body's own immune system mistakenly produces antibodies to an important part of the nerve signaling pathway -- the acetylcholine receptor (AChR). These antibodies that are in the circulatory system mark the AChR for destruction and can be removed with a technique called plasma exchange. The procedure can be beneficial; however, it removes a number of plasma components besides the AChR antibodies and this can result in unwanted side effects. Researchers in Japan experimented with another technique to remove the deleterious antibodies in a more specific manner. A synthetic material was developed that can selectively remove AChR antibodies, and the researchers conclude that the procedure is as effective as the conventional plasma exchange procedure with no serious complications. To maintain the beneficial effects of the plasma exchange immunosuppressive therapy was necessary as well. The research group concluded that the combination of selective removal of AChR antibodies and the use of immunosuppressive medications controlled myasthenia gravis in severely affected individuals who were unresponsive to other therapies. (Shibuya, N. et al. Journal of Neurology, Neurosurgery, and Psychiatry 1994; 57:578-581). Duchenne muscular dystrophy (DMD) was suspected in a boy who showed a few clinical signs of the disorder. The five-year-old boy had extremely high creatine kinase levels and experienced muscle cramps after exercise, although he had no calf hypertrophy or muscle weakness. Dystrophin analysis revealed that a certain segment of the dystrophin gene in both the boy and his grandfather is absent. The doctors describing these cases are not confident in a diagnosis of either Duchenne muscular dystrophy or Becker muscular dystrophy. Both the boy and his grandfather have normal muscle function with no indications of a progressive disease. In another family a similar deletion of the dystrophin gene resulted in similar clinical features not characteristic of Duchenne muscular dystrophy. The area deleted in these individuals is not the gene region generally found to be deleted in Duchenne muscular dystrophy. (Collins, A.L. et al. Journal of Medical Genetics 1994; 31:505-506). Dystrophin expression in mdx mouse muscle through the use of an adenoviral vector (gene-carrying vehicle) is being explored by several research groups. It is known that an altered adenovirus can be made to successfully carry and control a version of the dystrophin gene in muscle tissue. Also, it is promising that the altered virus for use in gene therapy is believed to be safe in that it would be incapable of causing a viral infection. However, a French research group injecting a dystrophin- adenoviral vector into mouse muscle found that trauma occurred at the site of injection. This was not observed in a previous study done by other researchers and the scientists are uncertain as to the cause. Indications are that the trauma observed may be overcome. Researchers conclude overall, from the experiments performed thus far, that adenoviral vectors have great promise as tools for Duchenne muscular dystrophy gene therapy. However, thorough evaluation of their safety and efficiency must be completed before their use as gene carriers may be tested in humans. (Alameddine, H.S. et al. Neuromuscular Disorders 1994; 4:193-203). cc: Bob Broedel -- ALS Interest Group [bro@huey.met.fsu.edu] --- MDA -- Working to find the cure for neuromuscular disease (7)=====Riluzole Trial Sites========== According to a memoramdum from the ALS Association, dated 14 July 1993 from Lynn Klein RN, the U.S. centers for the Riluzole study are at the following locations. There are no openings, but one would assume (I think) that the people involved with the study could be a possible source of information about the effectiveness of Riluzole. Robert G. Miller, MD California Pacific Medical Center Department of Neurology 3700 California Street East San Francisco CA 94118 TEL 415-750-6261 Theodore L. Munsat, MD New England Medical Center Department of Neurology 750 Washington Street Boston MA 02111 TEL 617-959-5855 Robert Sufit, MD Northwestern University Medical School Department of Neurology 233 E. Erie, Suite 500 Chicago IL 60611-2905 TEL 312-908-1774 Yadollah Harati, MD Baylor College of Medicine Department of Neurology 6550 Fannin, Suite 1801 Houston TX 77030 TEL 713-794-7393 Jeffrey D. Rothstein, MD Johns Hopkins School of Medicine Department of Neurology 600 N. Woolfe Street Baltimore MD 21287 TEL 410-955-6435 == end of als 120 ==