10) Functional & NeuroPhysiological Evidence of the Efficacy of Trophic Pharmacotherapy using AdrenoCorticoTrophic Hormone Analog in Experimental Allergic EncephaloMyelitis Summary: One possible approach to the treatment of MS could be to try to repair Neurological damage as it occurs. This might be done by using analogues of naturally occurring Hormones or chemicals that support nerve growth and repair. In this paper, the effectiveness of one such drug (AdrenoCorticoTrophic Hormone analogue) was tested on an animal (rat) model of MS. A variety of neurological parameters were studied. Repeated subcutaneous injections suppressed the development of disease symptoms in the rats and improved motor function (movement) as well as the time it took the animals to react after being touched by a hot object. Other more specific neurological parameters were also improved by the drug. Therefore, this study suggests that the Neurological repair approach to MS treatment might indeed be valuable in helping to restore motor function affected people. Much more study is necessary, however, before this particular treatment can be tried on people. HJ Duckers, RP Vandokkum, J Verhaagen, FHL Dasilva, WH Gispen NeuroScience 71: 2 (MAR 1996) Page(s) 507-521 WH Gispen, Univ Utrecht, Fac Med Rudolf Magnus Inst NeuroSci, Dept Med Pharmacol, 3521 Gd Utrecht, Netherlands   11) Cell-Cell Interactions During the Migration of Myelin-Forming Cells Transplanted in the DeMyelinated Spinal Cord Summary: The authors transplanted Myelin-forming cells into mice that had damaged Nerve cells. The cells were transplanted at a distance from the damaged site to see if the cells would move to the damaged area after transplantation. The transplanted cells called (Schwann cells) were found at the damaged site showing that these cells can indeed move in adult mice to a site of damage. The authors go on to describe the exact locations of these cells and the possible route of migration. They conclude that the movement pattern of these repair cells is determined by a number of differenT-Cell types in the Central Nervous System of the mouse and because there are a number of differenT-Cells involved in the process it must be quite complex. A Baronvanevercooren, V Avellanaadalid, A Benyouneschennoufi, A Gansmuller, B Naitoumesmar, L Vignais Glia 16: 2 (FEB 1996) Page(s) 147-164 A Baronvanevercooren, Hop La Pitie Salpetriere, Inserm U134, Lab NeuroBiol Cellulaire, 47 BVD Hop, F-75651 Paris 13, France 12) Pentoxifylline, a Phosphodiesterase Inhibitor, Induces Immune Deviation in Multiple Sclerosis Summary: Drugs which can modify the Immune System are potential candidates for MS therapy. T-Cells are integral components of the Immune System and are thought to play a role in the development of the disease. These cells produce compounds called Cytokines which attract and stimulate other Immune cells. A certain type of T-Cells called T-Helper type 1 (Th1) produce Cytokines that cause inflammation whereas a second set of T-Cells called T helper type 2 (Th2) produce Cytokines which stimulate B-Cells to produce AntiBodies. Immunotherapy of AutoImmune Diseases such as MS may be achieved by inhibiting the production of Cytokines from Th1 cells and stimulating Cytokine production of Th2. The scientists examined a compound called Pentoxifylline (PTX) which has been found to inhibit the production of some Th1 Cytokines and stimulates the production of some Th2 cytokines. Eight patients with Relapsing/Remitting MS were treated with PTX and Cytokine levels were measured in their blood. Two inflammatory Cytokines called Tumor Necrosis Factor alpha and InterLeukin-12 (the Th1 type) were found to be significantly decreased whereas InterLeukin-4 and -10 (the Th2 type) were found to be elevated in the MS patients treated with PTX. These results indicate that PTX modulates the Immune System in a favorable way and may have potential benefits as a treatment for MS. More studies are needed. P Rieckmann, F Weber, A Gunther, S Martin, A Bitsch, A Broocks, B Kitze, T Weber, T Borner, S Poser Journal of NeuroImmunology 64: 2 (FEB 1996) Page(s) 193-200 P Rieckmann, Univ Wurzburg, Neurol Klin & Poliklin, Josef Schneider Str 11, D-97080 Wurzburg, Germany   13) Impact of Aerobic Training on Fitness & Quality of Life in Multiple Sclerosis Summary: Fifty-four MS patients were grouped into either an exercise group (EX) or nonexercise group (NEX). The EX group underwent 3 X 40 minute sessions per week of leg and arm exercises. At the beginning of the study and after 15 weeks of aerobic training the participants were measured for various fitness factors including aerobic capacity, isometric strength, body composition, and blood lipids. Various other factors, such as daily activities, mood, fatigue and disease status were monitored in both groups. The EX group showed a number of improvements over the NEX group such as improved bowel and bladder function, upper and lower extremity strength, and aerobic capacity. There were also significant decreases in skinfolds, triglyceride, and very-low-density lipoprotein (VLDL). After five weeks depression and anger levels were lower and after ten weeks there was a reduction in fatigue. In general, the exercise improved the quality of life and resulted in improved fitness in the MS patients studied. JH Petajan, E Gappmaier, AT White, MK Spencer, L Mino, RW Hicks Annals of Neurology 39: 4 (APR 1996) Page(s) 432-441 JH Petajan, Univ Utah, Dept Neurol, Salt Lake City, UT 84112 USA   14) Safety Profile of Copolymer-1 (Copaxone): Cumulative Experience in United States & Israel Summary: This article summarizes the data accumulated so far regarding the treatment results of Copolymer 1 (Copaxone) on MS. A total of 857 patients to date (mainly with Relapsing/Remitting MS) have been enrolled in various trials. The typical dose of Copaxone was 20 milligrams by daily injection for at least one year and sometimes for more than 10 years. The most common side effect of the drug was redness and inflammation at the injection site and the most adverse event, which occurred in 10% of patients, was a whole body reaction including flushing, chest tightness, anxiety, rapid and irregular heart beat and was acute and transient. The authors suggest that the use of Copaxone appears to be well tolerated and suitable for self-administration by MS patients. AD Korczyn, P Nisipeanu Journal of Neurology 243: 4 Suppl. 1 (APR 1996) Page(s) S23-S26 AD Korczyn, Sackler Fac Med, IL-69978 Ramat Aviv, Israel 15) ImmunoGlobulins Reactive with Myelin Basic Protein Promote CNS ReMyelination Summary: This study tested the idea that AntiBodies directed against Myelin Basic Protein might help Remyelination caused by Immune mediated DeMyelinating diseases like MS. As an animal model of MS, they used mice infected with Theiler's Virus. These mice develop extensive DeMyelination and inflammation and show relatively low levels of ReMyelination. When the mice were treated with AntiBodies specifically directed against Myelin Basic Protein, they responded by increasing their production of new Myelin. Also, essentially no inflammatory cells were found in the ReMyelinated lesions, even though the virus was still present in the Spinal Cord. These results suggest that AntiBodies against Myelin proteins may potentially promote Myelin repair in individuals with MS. M Rodriguez, DJ Miller, VA Lennon Neurology 46: 2 (FEB 1996) Page(s) 538-545 M Rodriguez, Mayo Clin & Mayo Fdn, Mayo Med Sch, Dept Immunol, Rochester, MN 55905 USA 16) Side Effect Profile of Interferon-ß-1b in MS: Results of an Open Label Trial Summary: 72 MS patients who had started Interferon-ß-1b therapy after its release as a treatment for MS were studied. The purpose was to see which type of patient is most susceptible to side effects from this drug and which side effect are the most problematic. Skin reactions, flu-like symptoms, fatigue, leukopenia (decrease in white blood cells), new or worsened depression, and new or worsened headache were the most significant side effects associated with drug. The patients who suffered from fatigue and depression were the ones who were most likely to stop using Interferon-ß-1b. In addition, if the patients taking the drug had a chronic progression of the disease (even though the drug appeared to be beneficial in reducing the attack rate), they were also more likely to discontinue treatment. The authors suggest that in future clinical trials of Interferon-ß-1b, the side effects of fatigue and depression will have to be lessened in order to reduce the number of patients who stop taking the drug. LK Neilley, DS Goodin, DE Goodkin, SL Hauser Neurology 46: 2 (FEB 1996) Page(s) 552-554 DS Goodin, Univ Calif San Francisco, Dept Neurol, M-794, 505 Parnassus Ave, San Francisco, CA 94143 USA 17) Subcutaneously Insulin-like Growth Factor-I Reduces Clinical Deficits, Decreases Lesion Severity & Upregulates Synthesis of Myelin Proteins in Experimental AutoImmune EncephaloMyelitis Summary: In this study, the effects of a naturally occurring hormone called Insulin-like Growth Factor-1 (IGF-1) on treating MS was assessed using the animal model Experimental AutoImmune EncephaloMyelitis (EAE). IGF-1 treatment was started on the animals when they started showing definite clinical weakness. It was found that IGF-1 given subcutaneously (under the skin) or intravenously (injected into a vein) significantly reduced both clinical symptoms and lesion severity. IGF-1 treatment also appeared to promote Myelin regeneration, as assessed by an increase in production of Myelin components. These results suggest that IGF-1 may be useful in treating Multiple Sclerosis patients with active DeMyelination. DL Yao, X Liu, LD Hudson, HD Webster Life Sciences 58: 16 (MAR 15 1996) Page(s) 1301-1306 HD Webster, Nincds, NIH, Exptl Neuropathol Lab, Bldg 36, RM 4A29, Bethesda, MD 20892 USA 18) Intramuscular Interferon-ß-1alpha for Disease Progression in R/R Multiple Sclerosis Summary: This study reports on the findings of a phase III clinical trial of the drug Interferon-ß-1a (AvonexTM). It was carried out at a number of different medical centers and was initiated to determine if Interferon beta-1a was effective at slowing the progression of Neurological disability in Relapsing MS patients. 301 patients with Relapsing MS were randomly assigned to treatment or placebo control groups. Weekly injection of the drug (6 million units) or the placebo was given, and the patients were monitored for the time it took them to progress in their disability, as measured on a commonly used disability status scale called EDSS. It was found that patients treated with Interferon-ß-1a took a significantly longer time to progress one point further down the disability scale than those in the control group. The drug treated patients also had significantly fewer exacerbations and a significantly lower number and volume of Brain lesions assessed by Magnetic Resonance Imaging. Therefore, this major study concludes that Interferon-ß-1a (AvonexTM) is significantly beneficial in reducing the accumulation of permanent physical disability, exacerbation frequency, and disease activity in patients with Relapsing MS. Since this drug differs from standard therapies by actually slowing the progression of physical disability in MS patients rather than only treating the symptoms, its use may change the course of this disease. LD Jacobs, DL Cookfair, RA Rudick, RM Herndon, JR Richert, AM Salazar, JS Fischer, DE Goodkin, CV Granger, JH Simon, JJ Alam, DM Bartoszak, DN Bourdette, J Braiman, CM Brownscheidle, ME Coats, SL Cohan, DS Dougherty, RP Kinkel, MK Mass, FE Munschauer, RL Priore, PM Pullicino, BJ Scherokman, B Weinstockguttman, RH Whitman, WC Baird, M Fillmore, LM Bona, ME Colonruiz, BS Nadine, A Donovan, S Bennett, YM Kieffer, MA Umhauer, CE Miller, AK Kilic, EL Sargent, M Schachter, DW Shucard, V Weider, BA Catalano, JM Cervi, C Czekay, JL Farrell, JS Filippini, RC Matyas, KE Michienzi, M Ito, etal. Source Annals of Neurology 39: 3 (MAR 1996) Page(s) 285-294 LD Jacobs, Buffalo Gen Hosp, Dept Neurol, 100 High St, Buffalo, NY 14203 USA 19) Comparative Effects of Interferon-Consensus: Interferon-alpha(2a), and Interferon-ß(1b), on HLA Expression & LymphoProliferation: A Preclinical Model for Treatment of Multiple Sclerosis Summary: Interferon-ß-1b is a naturally occurring chemical in the immune system and is being used to treat Multiple Sclerosis. It is a member of a larger family of chemicals called type 1 Interferons. A synthetic protein has been created which is put together from the most common pieces of the different interferons. This new synthetic protein is called IFN-Con 1 for (Interferon-consensus 1), it has been shown to have greater biological activity in many situations when compared to the natural Interferons. Since IFN-Con 1 might prove to be more potent that Interferon-ß-1b in some regards, including the treatment of MS, its biological effects must be further studied. The authors of this paper investigated a number of different activities of IFN-Con 1. They concluded that in many ways it had effects that were similar to other Class 1 Interferons which might make it a possible candidate for use as a treatment for AutoImmune Diseases. S Dhibjalbut, H Jiang, QA Xia, L Blatt, KP Johnson, D Hilt Journal of Interferon and Cytokine Research 16: 3 (MAR 1996) Page(s) 195-200 S Dhibjalbut, Univ Maryland Hosp, Dept Neurol, 22 S 20) Selective Depletion of Myelin-Reactive T-Cells with the Anti-OX-40 AntiBody Ameliorates AutoImmune EncephaloMyelitis Summary: OX-40 is a protein which is produced in larger quantities on T-Cells that react against Myelin Basic Protein (MBP). These T-Cells are found at the site of inflammation at the onset of Experimental AutoImmune EncephaloMyelitis (EAE). The scientists in this study used a Toxin, called OX-40 ImmunoToxin, which binds and eliminates MPB-specific T-Cells without affecting other T-Cells. The destruction of these T-Cells resulted in an improvement of mice with this disease. The unique expression of OX-40 on the surface of these T-Cells may provide a new therapeutic strategy for the elimination of these T-Cells and a potential therapy for MS patients. AD Weinberg, DN Bourdette, TJ Sullivan, M Lemon, JJ Wallin, R Maziarz, M Davey, F Palida, W Godfrey, E Engleman, RJ Fulton, H Offner, AA Vandenbark Nature Medicine 2: 2 (FEB 1996) Page(s) 183-189  AD Weinberg, Providence Med Ctr, Earle a Chiles Res Inst, 4805 NE Glisan, Portland, OR 97213 USA 21) Intravenous Antigen Administration as Therapy for AutoImmune DeMyelinating Disease Summary: Experimental Allergic EncephaloMyelitis (EAE) is a DeMyelinating Disease induced in rodents, which is similar to MS. The authors have previously shown that the administration of high doses of Myelin Basic Protein (MBP) relieved some of the clinical signs and damaging effects of EAE through the destruction of MBP-specific T-Cell. In this study they demonstrate that multiple injections are required to acquire a therapeutic effect. This form of therapy works even after prolonged chronic disease. The inclusion of a Cytokine (InterLeukin-2) actually aggravated the clinical symptoms compared to the Antigen (MBP) alone. These experiments support the rationale for this kind of therapy which results in the decrease of specific AutoImmune T-Cells in mice. This type of strategy may be eventually used as a treatment for MS patients. MK Racke, JM Critchfield, L Quigley, B Cannella, CS Raine, HF Mcfarland, MJ Lenardo Annals of Neurology 39: 1 (JAN 1996) Page(s) 46-56 MK Racke, Washington Univ, Sch Med, Dept Neurol, Box 8111, 660 S Euclid Ave, St Louis, MO 63110 USA