=============================================================== == == == ----------- ALS INTEREST GROUP ----------- == == ALS Digest (#95, 14 April 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 == == 220+ 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 .. re: Jack's letter to the President 2 .. IGF-1 3 .. IGF-1 (Myotrophin) 4 .. IGF-1 (more) 5 .. dietary IGF-1 6 .. IGF-1 clinical trial sites, with openings 7 .. seeking ALS patients & care givers to interview (1) ===== re: Jack's letter to the President ========== Date : Tue, 12 Apr 1994 12:06:52 -0500 >From : Susan_Hales@infoman.com (Susan Hales) Subject: re: Jack's letter to the President from the ALS digest: >Now folks, you can wait for a reply or carry the momentum forward and >call, fax and write the President to respond. Have you friends call >and write. Do it starting on Monday. Call and ask him to respond to >Jack Norton's letter given to him in Minneapolis on April 8th. >White House Switchboard is 1-202-456-1111; FAX is 1-202-456-2461. >Maybe suggest he meets with Cindy and I while we are in DC. Everyone should know that the President and Vice President have email addresses. I'm sure they don't read the mail themselves, but it's as good as writing a letter or calling the White House switchboard, I suspect. You can send email to President Clinton at president@whitehouse.gov, and Vice President Gore at vicepresident@whitehouse.gov. --Sue ------------------------------------------ Susan Hay Hales, Technical Analyst Information Management Inc. 150 E. Ponce de Leon Avenue, Suite 430 Decatur, GA 30030 Phone: 404-377-4840 x306 Fax: 404-377-5116 Internet: Susan_Hales@infoman.com (2) ===== IGF-1 ========== Date : Tue, 12 Apr 94 10:33:05 EDT >From : vjs@xn.ll.mit.edu Subject: IGF-1 Can anyone tell me about IGF-1. I have a family member who is starting on a program using this. Does anyone have any first hand experience with it? Who would be the best knowledgeable people to contact regarding this particular medication regimin? vjs@ll.mit.edu (3) ===== IGF-1 (Myotrophin) ========== I was thinking that IGF-1 (Myotrophin) was a product of Cephalon, Inc. (145 Brandywine ParkWay; West Chester PA 19380; TEL 215-344-0200, FAX 215-344-0065). I did a MEDLINE search using the word "Myotrophin" and located such articles as these: 1. Myotrophin in human cardiomyopathic heart. 2. Myotrophin induces early response genes and enhances cardiac gene expression. 3. Myotrophin: purification of a novel peptide from spontaneously hypertensive rat heart that influences myocardial growth. They lead one to think that maybe Myotrophin is some kind of a generic term, rather than being a trademarked substance (?). Remember please, this is being written by a computer person ... not a research scientist or an MD or a patent lawyer, etc. Here are some quotations from the abstracts of the above mentioned articles. "Myotrophin purified from human dilated cardiomyopathic hearts is composed of a single polypeptide chain having an apparent molecular mass of 12 kD, determined by SDS-PAGE. The partial internal amino acid sequence of human myotrophin is very similar to that of rat myotrophin peptide T9." " We have identified and partially sequenced a soluble factor, myotrophin, from spontaneously hypertensive rat hearts and hypertrophic human hearts that enhances myocyte protein synthesis and stimulates myocardial cell growth." "The sequence of three internally liberated peptides containing 7-24 residues was determined. Based on the determined amino acid sequences of these peptides, this factor (designated myotrophin) appears to be a novel protein that shows no homology with any previously described growth factors. Myotrophin is present in human, dog, and rat hyper- trophied hearts (28-35% stimulation of protein synthesis over control) and in small amounts in normal hearts (5-6% stimulation)." I then located the following article via MEDLINE. ============================================= Title : Insulin-like growth factor-I: potential for : treatment of motor neuronal disorders. Author : Lewis ME; Neff NT; Contreras PC; Stong DB; : Oppenheim RW; Grebow PE; Vaught JL Source : Experimental Neurology 1993 Nov;124(1):73-88 Abstract : Motor neuronal disorders, such as the loss of spinal cord motor neurons in amyotrophic lateral sclerosis or the degeneration of spinal cord motor neuron axons in certain peripheral neuropathies, present a unique opportunity for therapeutic intervention with neurotrophic proteins. Normally, such proteins do not cross the blood-brain barrier, but spinal cord motor neuron axons and nerve terminals lie outside the barrier and thus may be targeted by systemic administration of protein growth factors. Insulin-like growth factor-I (IGF-I) receptors are present in the spinal cord, and, like members of the neurotrophin receptor family, IGF-I receptors mediate signal transduction via a tyrosine kinase domain. IGF-I was found to prevent the loss of choline acetyltransferase activity in embryonic spinal cord cultures, as well as to reduce the programmed cell death of motor neurons in vivo during normal development or following axotomy or spinal transection. Consistent with earlier reports that IGF-I enhances motor neuronal sprouting in vivo, subcutaneous administration of IGF-I increases muscle endplate size in rats. Subcutaneous injections of IGF-I also accelerate functional recovery following sciatic nerve crush in mice, as well as attenuate the peripheral motor neuropathy induced by chronic administration of the cancer chemotherapeutic agent vincristine in mice. Doses of IGF-I that accelerate recovery from sciatic nerve crush in mice result in elevated serum levels of IGF-I which are similar to those obtained following subcutaneous injections of formulated recombinant human IGF-I (Myotrophin) in normal human subjects. Based on these findings, together with evidence of safety in animals and man, clinical trials of recombinant human IGF-I have been initiated in patients with amyotrophic lateral sclerosis and are planned to begin soon in patients with chemotherapy-induced peripheral neuropathies. No doubt the authors of this article could be considered knowledgable on this subject. Most of them work at Cephalon (see address above). (4) ===== IGF-1 (more) ========== I searched MEDLINE using the search-term "insulin-like growth factor 1". As a result, 374 documents were located, which indicates that there must be some IGF-1 experts out there. Here are some examples ... 1. Insulin-like growth factor 1 and its binding protein 1 during normal and diabetic pregnancies. 2. The nature of the trophic action of brain-derived neurotrophic factor, des(1-3)-insulin-like growth factor-1, and basic fibroblast growth factor ... 3. Long-term insulin treatment of vascular smooth muscle cells from rat aorta attenuates the synergistic effect of insulin on angiotensin II- and epider... 4. Comparative effects of insulin and insulin-like growth factor-1 on follicle-stimulating hormone-induced responses in porcine granulosa cells. 5. A similar pool of cyclic AMP phosphodiesterase in Xenopus oocytes is stimulated by insulin, insulin-like growth factor 1, and [Val12,Thr59]Ha-r... 6. Insulin-like growth factor-1 receptors and insulin-like growth factor-1-like activity in human primary breast cancer. 7. Insulin-like growth factor-1 therapy in diabetes: physiologic basis, clinical benefits, and risks. 8. Insulin-like growth factor-1: a prognostic factor of knee osteoarthritis. 9. Insulin-like growth factor 1 in patients with hypoglycaemia. DOCUMENT 2 OF 374 - SET SEARCH TERMS INSULIN-LIKE GROWTH FACTOR 1 =============================================== Title : The nature of the trophic action of brain-derived : neurotrophic factor, des(1-3)-insulin-like growth : factor-1, and basic fibroblast growth factor on : mesencephalic dopaminergic neurons developing in : culture. Author : Beck KD; Knusel B; Hefti F Source : Neuroscience 1993 Feb;52(4):855-66 MESH Headings: : Animal;/DE;Biological Transport/DE;Blotting, Northern;Northern;Cell Division/DE;Cell Survival/DE;Cells, Cultured;Cultured;/ME;Dopamine/ME;Embryo;/PD!;Fibroblast Growth Factor, Basic/PD!;Fibroblast Growth Factor, Basic!;Growth;Factor;Basic;Insulin-Like Growth Factor I/PD!;Insulin-Like Growth Factor I!;I;/CY!;Mesencephalon/CY!;Mesencephalon/ME;Mesencephalon!;Nerve Growth Factors/PD;Nerve Tissue Proteins/PD!;Nerve Tissue Proteins!;Tissue;Proteins;Neurites/DE;/UL;Neurites/UL;Neurons/CY!; Neurons/DE;Neurons/ME;Neurons!;Peptide Fragments/PD!;Peptide Fragments!; Fragments;Rats;Rats, Wistar;Wistar;/AN;RNA, Messenger/AN;RNA, Messenger/ME;Support, Non-U.S. Gov't;Non-U.S.;Gov't;Support, U.S. Gov't, Non-P.H.S.;U.S.;Non-P.H.S.;Support, U.S. Gov't, P.H.S.;P.H.S.;/GE; Tyrosine Hydroxylase/GE;Tyrosine Hydroxylase/ME : Abstract : Brain-derived neurotrophic factor, basic fibroblast : growth factor and des(1-3)-insulin-like growth factor-1, : a brain specific form of insulin-like growth factor-1, : were analysed, in the rat, for their influence on survival, : morphological growth, and transmitter-specific : differentiation of dopaminergic neurons in vitro. : Brain-derived neurotrophic factor, des-insulin-like growth : factor-1, and basic fibroblast growth factor were found : to differentially regulate development of dopaminergic : cells. Brain-derived neurotrophic factor stimulated : survival, the formation of primary neurites and dopamine : uptake activity. des-Insulin-like growth factor-1 was : most effective in promoting survival, stimulated dopamine : uptake less effectively than brain-derived neurotrophic : factor and did not alter the morphology of dopaminergic : cells. Basic fibroblast growth factor produced : comparatively mild increases in survival and dopamine : uptake, and slightly reduced neurite growth of the cells. : None of the factors stimulated the expression of the : tyrosine hydroxylase gene. : These findings suggest that (i) effective growth factors : may stimulate different, but partially overlapping, : molecular pathways during developmental differentiation, : (ii) none of the factors stimulates dopaminergic cell : differentiation comparable to the pronounced trophic : action of nerve growth factor on peripheral sympathetic : or basal forebrain cholinergic neurons, and : (iii) localization and effects of none of the factors : are compatible with a role as target-derived survival- : regulating neurotrophic factor. Address : : K.D. Beck; Division of Neurogerontology; Andrus Gerontology : Center; University of Southern California; Los Angeles CA : 90089 (5) ===== dietary IGF-1 ========== In a copyrighted article in FOOD CHEMICAL NEWS (March 21, 1994) entitled: BST OPPONENTS EXPECT CONGRESSIONAL INVESTIGATION OF TAYLOR ROLE "Opponents of recombinant bovine somatotropin (rBST) say they expect a congressional investigation into charges that Michael Taylor, Food and Drug Administration Deputy Commissioner for Policy, has a conflict of interest regarding the development of guidelines for genetically engineered foods and rBST." "Katherine Ozer, executive director of the National Family Farm Coalition, and University of Illinois scientist Dr. Samuel Epstein announced the expected investigation at a March 14 press conference. They said the congressional investigation also would look into "general health issues" regarding rBST. Members of Congress who may pursue an investigation include Rep. Sanders (I-Vt.), Rep. Obey (D-Wis.) and Sen. Feingold (D-Wis.), Ozer and Epstein said." < most of this copyrighted article deleted> "Epstein reiterated claims he made in a Feb. 14 letter to FDA Commissioner David Kessler that drinking rBST milk would increase breast cancer risk because of increased levels of insulin-like growth factor (IGF-1) and specific receptors in breast epithelium." "Levels of IGF-1 are twice as high in rBST meat and milk products; the excess is destroyed by heat treatment in cooking, but not by pasteurization, Epstein said." "He said infants are particularly sensitive to future carcinogenic effects of IGF-1. Infants would be exposed to a "100-fold excess in the safety margin." In addition to being a growth factor for human breast cancer cells, IGF-1 has also been associated with colon cancer, Epstein said." (6) ===== IGF-1 clinical trial sites, with openings ========== Clinical trials with Myotrophin (IGF-1) for ALS are being held at the following locations (openings are available). This information provided by the ALS Association. Stacy Rudnicki, MD University of Arkansas Medical Center 4301 West Markham Slot 500, Room 7B27 Little Rock AR 72205 TEL 501-686-5134 Kevin Felice, D O Department of Neurology University of Connecticut Health Center 263 Farmington Avenue Farmington CT 06030 TEL 203-679-3233 Marek Gawel, MD Division of Neurology Sunnybrook Health Science Center University of Toronto Clinic 2075 Bayview Avenue North York, Ontario M4N 3M5 CANADA TEL 416-480-4214 (7) ===== seeking ALS patients & care givers to interview ========== The Wilkerson Group is a medical research and consulting firm in New York and London. We work primarily for pharmaceutical, device, and diagnostic companies on a variety of projects. We are currently working for a client who has a product in development for ALS and we are recruiting patients and care givers to interview for this project. We are interested in talking about topics that include the current treatment environment, how much input patients and their families have in their treatment plan, reimbursement issues, where patients and families get new information about ALS and treatments, how care changes as ALS progresses, and what is wanted most in new treatments. The interview should take about 45 minutes. They will take place over the phone and can be scheduled at the interviewees convience. We would like to thank the participants with a donation to the ALS Association or other appropriate group. Interested participants can call the Wilkerson Group at 800-654-8667 and ask for Maureen McNulty. === = The Wilkerson Group, Inc. = 666 Third Avenue = New York New York 10017-4011 = TEL 212-557-1717 = FAX 212-972-1056 === == end of als 95 ==