<%@LANGUAGE="JAVASCRIPT" CODEPAGE="1252"%> Multiple Sclerosis: The Process and Treatments

A Promising Future

The last decade has brought many exciting discoveries about multiple sclerosis, leading investigators closer to finding a cause and a cure. The last decade has also yielded five disease-modifying agents that have all been shown to slow disease activity. Many individuals with MS may look forward to fewer and less severe relapses, and some may even experience a slowing of disease progression, as a result of these new drug therapies.

The momentum continues to build and the next decade holds tremendous promise for those with MS and the people who are close to them. More MS research than ever before is being conducted around the world. Devoted researchers and physicians continuously provide countless articles, publications, and news reports to bring new information about possible causes and new treatments to those diagnosed with this disorder.

As these individuals wait for more exciting advancements to arrive, they may also take advantage of the many symptom-management therapies available to them. With the assistance of their medical professionals, supportive family members and friends, along with a few lifestyle changes and a well-designed treatment plan, individuals with MS may look forward to an active, meaningful, and happy future.

Bibliography

Achiron A., Barak Y., Goren M., Gabbay U., et al., Intravenous Immune Globulin in Multiple Sclerosis: Clinical and Neuroradiological Results and Implications for Possible Mechanisms of Action, Clin. Exp. Immunol., May 1996, 104 Suppl. 1, pp. 67-70.

Achiron A., Barak Y., Goren M., Gabbay U., et al., Intravenous Immune Globulin in Multiple Sclerosis: Clinical and Neuroradiological Results and Implications for Possible Mechanisms of Action, Clin. Exp. Immunol., May 1996, 104 Suppl. 1, pp. 67-70.

Achiron A., Gilad R., Margalit R., Gabbay U., et al., Intravenous Gammaglobulin Treatment in Multiple Sclerosis and Experimental Autoimmune Encephalomyelitis: Delineation of Usage and Mode of Action, Journal of Neurology, Neurosurgery, and Psychiatry, Nov. 1994, 57 Suppl, pp. 57-61.

Achiron A., Miron S., Lavie V., et al., Dexanabinol (HU-211) effect on experimental autoimmune encephalomyelitis: implications for the treatment of acute relapses of multiple sclerosis, J Neuroimmunol 2000, Jan. 3, 102 (1), pp. 26-31.

Adorini L., Selective immunointervention in autoimmune diseases: lessons from multiple sclerosis, J Chemother 2001, Jun., 13 (3), pp. 219-34.

Alchem Laboratories Corporation, Dexanabinol Pharmos, Curr Opin Investig Drugs 2000, Dec., 1 (4), pp. 494-503.

Anderson O., Lycke J., Tollesson P.O., Svenningsson A., Runmarker B., Linde A.S., Astrom M., Gjorstrup P., Ekholm S., Linomide Reduces the Rate of Active Lesions in Relapsing-Remitting Multiple Sclerosis, Neurology, Oct. 1996, 47 (4), pp. 895-900.

Archer D.R., Cuddon P.A., Lipsitz D., Duncan I.D., Myelination of the Canine Central Nervous System by Glial Cell Transplantation – A Model for Repair of Human Myelin Disease, Nature Medicine, Jan. 1997, 3, pp. 54-59.

Ascherio A., Munger KL., Lennette ET., et al., Epstein-Barr Virus Antibodies and Risk of Multiple Sclerosis: A Prospective Study, JAMA, Dec 2001, 286(24), pp. 3083-3088.

Barkhof F., Van Waesbergie JH., Filippi M., et al., T(1) hypo intense lesions in secondary progressive multiple sclerosis: effect of interferon beta-1b treatment, Brain, July 2001, 124(Pt 7), pp 1396-402.

Bansil S., Cook S.D., Rohowsky-Kochan C., Multiple Sclerosis: Immune Mechanism and Update on Current Therapies, Annals of Neurology, May 1995, 37 suppl. 1, pp. S87-101.

Bansil S., Singhal B.S., Ahuja G.K., Ladiwala U., et al., Comparison between Multiple Sclerosis in India and the United States: A Case-Control Study, Neurology, Feb. 1996, 46 (2), pp. 385-7.

Barnes D., Hughes R.A., Morris R.W., Wade-Jones O., et al., Randomized Trial of Oral and Intravenous Methylprednisolone in Acute Relapses of Multiple Sclerosis, Lancet, Mar. 29, 1997, 349 (9056), pp. 902-6.

Baron-Van Evercooren A., Future Prospects in Transplantation, Annals of Neurology, 1994, 36 Suppl., pp. 151-6.

Becker C.C., Gidal B.E., Fleming J.O., Immunotherapy in Multiple Sclerosis, Part 1, American Journal of Health Systems Pharmacy, Sep. 15, 1995, 52 (18), pp. 1985-2000.

Becker C.C., Gidal B.E., Fleming J.O., Immunotherapy in Multiple Sclerosis, Part 2, American Journal of Health Systems Pharmacy, Oct. 1, 1995, 52 (19), pp. 2105-20.

Bergstrom T., Herpesviruses—a rationale for antiviral treatment in multiple sclerosis, Antiviral Res 1999, Feb., 4 (1), pp. 1-19.

Bergstrom T., Several options for antiviral treatment trials in multiple sclerosis—but which targets should be selected?, Expert Opin Pharmacother 2000, Sep., 1 (6), pp. 1087-90.

Beutler E., Sipe J.C., Romine J.S., Koziol J.A., et al., The Treatment of Chronic Progressive Multiple Sclerosis with Cladribine, Proc. National Academy of Science USA, Feb. 20, 1996, 93 (4), pp. 1716-20.

Bieklekova B., Goodwin B., Richert N., et al., Encephalitogenic potential of the myelin basic protein peptide (amino acids 83-99) in multiple sclerosis: results of a phase II clinical trial with an altered peptide ligand, Nat. Med., Oct. 2000, 6(10), pp. 1167-75.

Bieklekova B., Lincoln A., McFarland H., et al., Therapeutic potential of phosphodiesterase-4 and –3 inhibitors in Th1-mediated autoimmune diseases, J Immunol, Jan. 2000, 164(2), pp. 1117-24.

Boccaccio G.L., Steinman L., Multiple Sclerosis: From a Myelin Point of View, Journal of Neuroscience Research, Sep. 15, 1996, 45 (6), pp. 647-54.

Brenner T., Arnon R., Sela M., et al., Humoral and cellular immune responses to Copolymer 1 in multiple sclerosis patients treated with Copaxone, J. Neuroimmunol, Apr. 2001, 115(1-2), pp. 152-60.

Brod S.A., Nelson L., Jin R., Wolinsky J.S., Ingested interferon alpha induces MX mRNA, Cytokine 1999, Jul., 11 (7), pp. 492-9.

Brod S.A., Lindsey J.W., Vriesendorp F.S., et al., Ingested IFN-alpha: results of a pilot study in relapsing-remitting MS, Neurology 2001, Sep 11, 57 (5), pp. 845-52.

Brody J.E., ‘Hair of Dog’ Tried as Cure for Autoimmune Disease, The New York Times, Oct. 18, 1994, Sec. C., p. 1, col. 1.

Bruck W., Schmied M., Suchanek G., Bruck Y., et al., Oligodendrocytes in the Early Course of Multiple Sclerosis, Annals of Neurology, Jan. 1994, 35 (1), pp. 65-73.

Brusaferri F., Candelise L., Steroids for multiple sclerosis and optic neuritis: a meta-analysis of randomized controlled clinical trials, J. Neurol., June 2000, 247(6), pp. 435-42.

Burks J.S., Johnson K.P., Multiple Sclerosis – Diagnosis, Medical Management, and Rehabilitation, Demos Medical Publishing, New York, 2000.

Buyse B., Demedts M., Meekers J., Vandegaer L., et al., Respiratory Dysfunction in Multiple Sclerosis: A Prospective Analysis of 60 Patients, European Respiratory Journal, Jan. 1997, 10 (1), pp. 139-45.

Calabresi P.A., Stone L.A., Bash C.N., Frank J.A., et al., Interferon Beta Results in Immediate Reduction of Contrast-Enhanced MRI Lesions in Multiple Sclerosis Patients Followed by Weekly MRI, Neurology, May 1997, 48 (5), pp. 1446-8.

Carroll D., Dorman J., Living Well with MS, HarperCollins Publishers, New York, 1993.

Chen M., Gran B., Costello K., et al., Glatiramer acetate induces a TH2-biased response and cross reactivity with myelin basic protein in patients with MS, Mult. Scler., Aug. 2001, 7(4), pp. 209-19.

Claudio L., Brosnan C.F., Effects of Prazosin on the Blood-Brain Barrier During Experimental Autoimmune Encephalomyelitis, Brain Research, Oct. 30, 1992, 594 (2), pp. 233-43.

Clayman C., The Human Body, Dorling Kindersley Publishing, New York, 1995.

Coles AJ., Wing MG., Molyneux P., et al., Monoclonal antibody treatment exposes three mechanisms underlying the clinical course of multiple sclerosis, Ann. Neurol., Sep. 1999, 46(3), pp. 296-304.

Confavreux C., Saddier P., Grimaud J., Moreau T., et al., Risk of Cancer from Azathioprine Therapy in Multiple Sclerosis: A Case-Control Study, Neurology, June 1996, 46 (6), pp. 1607-12.

Correale J., Lund B., McMillan M., et al., T cell vaccination in secondary progressive multiple sclerosis, J Neuroimmunol 2000, Jul., 24, 107 (2), pp. 130-9.

Cotton P., Options for Multiple Sclerosis Therapy, JAMA, Nov. 9, 1994, 272 (18), p. 1393.

Davis W.M., Multiple Sclerosis: Continuing Mysteries and Current Management, Drug Topics, June 19, 2000.

De Groot C.J., Ruuls S.R., Theeuwes J.W., Dijkstra C.D., et al., Immunocytochemical Characterization of the Expression of Inducible and Constitutive Isoforms of Nitric Oxide Synthase in Demyelinating Multiple Sclerosis Lesions, Journal of Neuropathology Exp Neurol, Jan. 1997, 56 (1), pp. 10-20.

De Keyser J., Zwanikken C., Oral Versus Intravenous Corticosteroids in Acute Relapses of Multiple Sclerosis, Lancet, June 7, 1997, 349 (9066), p. 1696.

De Lafuente D., Transplant Provides Hope to MS Patients, Chicago Sun-Times, Nov. 22, 1996.

Drew P.D., Chavis J.A., Female sex steroids: effects upon microglial cell activation, J Neuroimmunol 2000, Nov. 1, 111 (1-2), pp. 77-85.

Durelli L., Bongioanni M.R., Cavallo R., Ferrero B., Ferri R., Ferrio M.F., Bradac G.B., Riva A., Vai S., Geuna M., et al, Chronic Systemic High-Dose Recombinant Interferon Alfa-2a Reduces Exacerbation Rate, MRI Signs of Disease Activity, and Lymphocyte Interferon Gamma Production in Relapsing-Remitting Multiple Sclerosis, Neurology, Mar. 1994, 44 (3 pt. 1), pp. 406-13.

Durelli L., Bongioanni M.R., Ferrero B., Ferri R., et al., Interferon Alpha-2a Treatment of Relapsing-Remitting Multiple Sclerosis: Disease Activity Resumes After Stopping Treatment, Neurology, Jul. 1996, 47 (1), pp. 123-9.

Durelli L., Ferrero B., Oggero A., et al., Liver and thyroid function and autoimmunity during interferon-beta 1b treatment for MS, Neurology, Oct. 2001, 57(8), pp. 1363-70.

Dyke HJ., Montana JG., Update on the therapeutic potential of PDE4 inhibitors, Expert Opin. Investig. Drugs, Jan. 2002, 11(1), pp. 1-13.

Edan G., Miller D., Clanet M., Confavreux C., et al., Therapeutic Effect of Mitoxantrone Combined with Methylprednisolone in Multiple Sclerosis: A Randomized Multicentre study of Active Disease Using MRI and Clinical Criteria, Journal of Neurology, Neurosurgery, and Psychiatry, Feb. 1997, 62 (2), pp. 112-118.

Epplen C., Jackel S., Santos E.J., D’Souza M., et al., Genetic Predisposition to Multiple Sclerosis as Revealed by Immunoprinting, Annals of Neurology, Mar. 1997, 41 (3), pp. 341-52.

Esparza M.L., Sasaki S., Kesteloot H., Nutrition, Latitude, and Multiple Sclerosis Mortality: An Ecologic Study, American Journal of Epidemiology, Oct. 1, 1995, 142 (7), pp. 733-7.

Fazekas F., Deisenhammer F., Strasser-Fuchs S., Nahler G., Mamoli B., Randomised Placebo-Controlled Trial of Monthly Intravenous Immunoglobulin Therapy in Relapsing-Remitting Multiple Sclerosis, Lancet, Mar. 1, 1997, 349 (9052), pp. 589-93.

Filippi M., Capra R., Campi A., Colombo B., et al., Triple Dose of Gadolinium-DTPA and Delayed MRI in Patients with Benign Multiple Sclerosis, Journal of Neurology, Neurosugery, and Psychiatry, May 1996, 60 (5), pp. 526-30.

Fridkis-Hareli M., Stern JN., Fugger L., et al., Synthetic peptides that inhibit binding of the myelin basic protein 85-99 epitode to multiple sclerosis-associated HLA-DR2 molecules and MBP-specific T-cell responses, Hum. Immunol, Aug. 2001, 62(8), pp. 753-63.

Galan M., The Defending Army, Time-Life Books, Richmond, VA, 1993.

Galetta SL., The Controlled High Risk Avonex® Multiple Sclerosis Trial (CHAMPS STUDY), J. Neurophthalmol, Dec. 2001, 21(4), pp. 292-5.

Gay F.W., Drye T.J., Dick G.W., Esiri M.M., The Application of Multifactorial Cluster Analysis in the Staging of Plaques in Early Multiple Sclerosis. Identification and Characterization of the Primary Demyelinating Lesion, Brain, Aug. 1997, 120 (Pt 8), pp. 1461-83.

Goodin DS., Therapeutic developments in multiple sclerosis, Expert Opin. Investig. Drugs, Apr. 2000, 9(4), pp. 655-70.

Goodin D.S., Frohman E.M., Garmany G.P., et al., Disease modifying therapies in multiple sclerosis: Subcommittee of the American Academy of Neurology and the MS Council for Clinical Practice Guidelines, Neurology 2002, 58, pp. 169-178.

Goodkin D., Interferon Beta-1b, The Lancet, Oct. 15, 1994, 344, pp. 1057-60.

Goodkin D., Role of Steroids and Immunosuppression and Effects of Interferon-Beta 1b in Multiple Sclerosis, WJM, Sept. 1994, 161 (3), pp. 292-8.

Goodkin D.E., Rudick R.A., VanderBrug Medendorp S., Daughtry M.M., Schwetz K.M., Fisher J., Van Dyke C., Low-dose (7.5 mg) Oral Methotrexate Reduces the Rate of Progression in Chronic Progressive Multiple Sclerosis, Annals of Neurology, Jan. 1995, 37 (1), pp. 30-40.

Goodkin D.E., Rudick R.A., VanderBrug-Medendorp S., Daughtry M.M., et al., Low-Dose Oral Methotrexate in Chronic Progressive Multiple Sclerosis: Analysis of Serial MRI’s, Neurology,

Nov. 1996, 47 (5), pp. 1153-7.

Grinspan J.B., Stern J., Franceschini B., Yasuda T., et al., Protein Growth Factors as Potential Therapies for Central Nervous System Demyelinative Disorders, Annals of Neurology, 1994, 36 Suppl., pp. 140-2.

Guttmann C.R., Ahn S.S., Hsu L., Kikinis R., et al., The Evolution of Multiple Sclerosis Lesions on Serial MR, American Journal of Neuroradiology, Aug. 1995, 16 (7), pp. 1481-91.

Haegert D.G., Marrosu M.G., Genetic Susceptibility to Multiple Sclerosis, Annals of Neurology, Dec. 1994, 36 Suppl. 2, pp. S204-10.

Hammond S.R., McLeod J.G., Macaskill P., English D.R., Multiple Sclerosis in Australia: Socioeconomic Factors, Journal of Neurology, Neurosurgery, and Psychiatry, Sept. 1996, 61 (3), pp. 311-3.

Hartung H.P., Archelos J.J., Zielasek J., Gold R., et al., Circulating Adhesion Molecules and Inflammatory Mediators in Demyelination: A Review, Neurology, June 1995, 45 (6 Suppl. 6), pp. 22-32.

Hooper D.C., Bagasra O., Marini J.C., Zborek A., et al, Prevention of Experimental Allergic Encephalomyelitis by Targeting Nitric Oxide and Peroxynitrite: Implications for the Treatment of Multiple Sclerosis, Proc. National Academy of Science USA, Mar. 18, 1997, 94 (6), pp. 2528-33.

Huang Z., Ducharme Y., MacDonald D., et al., The next generation of PDE4 inhibitors, Curr. Opin. Chem. Biol., Aug. 2001, 5(4), pp. 432-8.

IFNB Multiple Sclerosis Study Group and the University of British Columbia MS/MRI Analysis Group, Neutralizing Antibodies During Treatment of Multiple Sclerosis with Interferon Beta-1b: Experience During the First Three Years, Neurology, Oct. 1996, 47 (4), pp. 889-94.

Jacobs L., Beck R., Simon J., et al., Intramuscular Interferon Beta-1A Therapy Initiated during a First Demyelinating Event in Multiple Sclerosis, N. Engl. J. Med., 343, pp. 898-904.

Jacobs L.D., Cookfair D.L., Rudick R.A., et al., Intramuscular Interferon Beta-1a for Disease Progression in Relapsing Multiple Sclerosis, Annals of Neurology, Mar. 1996, 39 (3), pp. 285-94.

Jacobs L., Goodkin D.E., Rudick R.A., Herndon R., Advances in Specific Therapy for Multiple Sclerosis [Review], Current Opinion in Neurology, June 1994, 7 (3), pp. 250-4.

Jain K.K., Evaluation of mitoxantrone for the treatment of multiple sclerosis, Expert Opin, Investig Drugs 2000, May, 9 (5), pp. 1139-49.

Johnson K.P., Brooks B.R., Ford C.C., et al., Sustained clinical benefits of glatiramer acetate in relapsing multiple sclerosis patients observed for 6 years, Multiple Sclerosis (2000), 6, pp. 255-266.

Kalb R.C., Multiple Sclerosis, The Questions You Have – The Answers You Need, second edition, Demos Medical Publishing, New York, 2000.

Kappos L., Polman C., Pozzilli C., Final analysis of the European multicenter trial of IFN beta-1b in secondary progressive MS, Neurology, Dec. 2001, 57(11), pp. 1969-75.

Karussis D.M., Lehmann D., Slavin S., Vourka-Karussis U., Mizrachi-Koll R., Ovadia H., Ben-Nun A., Kalland T., Abramsky O., Inhibition of Acute, Experimental Autoimmune Encephalomyelitis by the Synthetic Immunomodulator Linomide, Annals of Neurology, Nov. 1993, 34 (5), pp. 654-60.

Karussis D.M., Meiner Z., Lehmann D., Gomori J.M., Schwarz A., Linde A., Abramsky O., Treatment of Secondary Progressive Multiple Sclerosis with the Immunomodulator Linomide: A Double-Blind, Placebo-Controlled Pilot Study with Monthly Magnetic Resonance Imaging Evaluation, Neurology, Aug. 1996, 47 (2), pp. 341-6.

Katz A., Protein Offers Hope in MS Fight, New Haven Register, May 29, 1995, sec.A, p.3.

Khan OA., Tselis AC., Kamholz JA., et al., A prospective, open-label treatment trial to compare the effect of IFN beta-1a (Avonex), IFNbeta-1b (Betaseron), and glatiramer acetate (Copaxone) on the relapse rate in relapsing-remitting multiple sclerosis, Eur. J. Neurol., Mar. 2001, 8(2), pp. 141-8.

Kidd D., Thorpe J.W., Kendall B.E., Barker G.J., et al., MRI Dynamics of Brain and Spinal Cord in Progressive Multiple Sclerosis, Journal of Neurology, Neurosurgery, and Psychiatry, Jan. 1996, 60 (1), pp. 15-9.

Kim S., Liva S.M., Dalal M.A., et al., Estriol ameliorates autoimmune demyelinating disease: implications for multiple sclerosis, Neurology 1999, Apr. 12, 52 (6), pp. 1230-8.

Lai M., Hodgson T., Gawne-Cain M., Webb S., et al., A Preliminary Study into the Sensitivity of Disease Activity Detection by Serial Weekly Magnetic Resonance Imaging in Multiple Sclerosis, Journal of Neurology, Neurosurgery, and Psychiatry, Mar. 1996, 60 (3), pp. 339-41.

Lassmann H., Suchanek G., Ozawa K., Histopathology and the Blood-Cerebrospinal Fluid Barrier in Multiple Sclerosis, Annals of Neurology, 1994, 36 Suppl., pp. 42-6.

Lechtenberg R., Multiple Sclerosis Fact Book, F.A. Davis Company, 1988.

Liebsch R., Kornhuber M.E., Dietl D., Grafin von Einsiedel H., et al., Blood-CSF Barrier Integrity in Multiple Sclerosis, Acta. Neurol. Scand., Dec. 1996, 94 (6), pp. 404-10.

Lin KC., Castro AC., Very late antigen 4 (VLA4) antagonists as anti-inflammatory agents, Curr. Opin. Chem. Biol., Aug. 1998, 2(4), pp. 453-7.

Lublin F.D., Reingold S.C., Defining the Clinical Course of Multiple Sclerosis: Results of an International Survey, Neurology, Oct. 1996, 46, pp. 907-911.

Lugaresi A., Caporale C., Farina D., et al., Low-dose oral methotrexate treatment in chronic progressive multiple sclerosis, Neurol. Sci., Apr. 2001, 22(2), pp. 209-10.

Makhlouf K., Weiner H.L., Khoury S.J., Potential of beta (2)-Adrenoceptor Agonists as Add-On Therapy for Multiple Sclerosis: Focus on Salbutamol (Albuterol), CNS Drugs 2002, 16 (1), pp.1-8.

Maron R., Slavin AJ., Hoffmann E., et al., Oral tolerance to copolymer 1 in myelin basic protein (MBP) TCR transgenic mice: cross-reactivity with MBP-specific TCR and differential induction of anti-inflammatory cytokines, Int. Immunol., Feb. 2002, 14(2), pp. 131-8.

Matsumoto Y., Characterization of T cell receptor (TCR) of organ-specific autoimmune disease-inducing T cells and TCR-based immunotherapy with DNA vaccines, J Neuroimmunol 2000, Oct. 2, 110 (1-2), pp. 1-12.

Mauch E., Lambacher R., Rauer S., Wagner U., et al., The Course of Multiple Sclerosis Under Cyclophosphamide or Mitoxantrone as Compared with the Spontaneous Course or Cortisone/ACTH, Neurology, Psychiatry and Brain Research, 1993, 1, pp. 220-7.

McDonald W.I., Compston A., Edan G., Goodkin D., et al, Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis, Annals of Neurology, July 2001, 50(1), pp.121-7.

McFarland HI., Lobito AA., Johnson MM., et al., Effective antigen-specific immunotherapy in the marmoset model of multiple sclerosis, J. Immunol., Feb. 2001, 166(3), pp. 2116-21.

Medaer R., Stinissen P., Truyen L., Raus J., Zhang J., Depletion of Myelin-Basic-Protein Autoreactive T-Cells by T-Cell Vaccination: Pilot Trial in Multiple Sclerosis, Lancet, Sept. 23, 1995, 346 (8978), pp. 807-8.

Mikol DD., Treat Early, but Treat Hard: Interferon-beta Dose Makes a Difference, J. Neurophthalmol, Dec. 2001, 21(4), 237-9.

Milanese C., La Mantia L., Salmaggi A., Eoli M., A Double Blind Study on Azathioprine Efficacy in Multiple Sclerosis: Final Report, Journal of Neurology, May 1993, 240 (5), pp. 295-8.

Miller J. L., Mitoxantrone receives multiple-sclerosis indication, Am J Health Syst Pharm. 2000, Nov. 15, 57 (22), pp. 2238-2040.

Mitchell G., Update on Multiple Sclerosis Therapy [Review], Medical Clinics of North America, Jan. 1993, 77 (1), pp. 231-49.

Mohr D.C., Goodkin D.E., Likosky W., Gatto N., et al., Treatment of Depression Improves Adherence to Interferon Beta-1b Therapy for Multiple Sclerosis, Archives of Neurology, May 1997, 54 (5), pp. 531-3.

Moreau T., Thorpe J., Miller D., Moseley I., Hale G., Waldmann H., Clayton D., Wing M., Scolding N., Compston A., Preliminary Evidence from Magnetic Resonance Imaging for Reduction in Disease Activity after Lymphocyte Depletion in Multiple Sclerosis, Lancet, July 30, 1994, 344 (8918), pp. 298-301.

Morgan E.E., Nardo C.J., Diveley J.P., et al., Vaccination with a CDR2 BV6S2/6S5 peptide in adjuvant induces peptide-specific T-cell responses in patients with multiple sclerosis, J Neurosci Res 2001, May 1, 64 (3), pp. 298-301.

Morrison W., Nelson J., Environmental Triggers in Multiple Sclerosis. Fact or Fallacy? Axone, Sept. 1994, 16 (1), pp. 23-6.

Multiple Sclerosis Collaborative Research Group, Intramuscular Interferon Beta-1a for Disease Progression in Relapsing Multiple Sclerosis, Annals of Neurology, Mar. 1996, 39 (3), pp. 285-94.

Narayanan S., De Stefano N., Francis GS., et al., Axonal metabolic recovery in multiple sclerosis patients treated with interferon beta-1b, J. Neurol., Nov. 2001, 248(11), pp. 979-86.

Neilley L.K., Goodin D.S., Goodkin D.E., Hauser S.L., Side Effect Profile of Interferon Beta-1b in MS: Results of an Open Label Trial, Neurology, Feb. 1996, 46 (2), pp. 552-4.

Newman T.A., Woolley S.T., Hughes P.M., et al., T-cell-and macrophage-medicated axon damage in the absence of a CNS-specific immune response: involvement of metalloproteinases, Brain 2001, Nov., 124 (Pt 11), pp. 2203-14.

Noseworthy J.H., Clinical Trials in Multiple Sclerosis [Review], Current Opinion in Neurology & Neurosurgery, Apr. 1993, 6 (2), pp. 209-15.

Noseworthy J.H., Lucchinetti C., Rodriguez M., et al., Multiple Sclerosis, The New England Journal of Medicine, Sep.28, 2000, pp. 938-952.Noseworthy J.H., O’Brien P.C., van Engelen B.G., Rodriguez M., Intravenous Immunoglobulin Therapy in Multiple Sclerosis: Progress from Remyelination in the Theiler’s Virus Model to a Randomised, Double-Blind, Placebo-Controlled Clinical Trial, Journal of Neurology, Neurosurgery, and Psychiatry, Nov. 1994, 57 Suppl., pp. 11-4.

Ozawa K., Suchanek G., Breitschopf H., Bruck W., Patterns of Oligodendroglia Pathology in Multiple Sclerosis, Brain, Dec. 1994, 117 (Pt. 6), pp. 1311-22.

Panitch H.S., Influence of Infection on Exacerbations of Multiple Sclerosis, Annals of Neurology, 1994, 36 Suppl, pp. S25-8.

Paolillo A., Coles A.J., Molyneux P.D., et al., Quantitative MRI in patients with secondary progressive MS treated with monoclonal antibody Campath IH, Neurology 1999, Sep. 11, 53 (4), pp. 751-7.

Patti F., Cataldi M.L., Nicoletti F., et al., Combination of cyclophosphamide and interferon-beta halts progression in patients with rapidly transitional multiple sclerosis, J Neurol Neurosurg Psychiatry 2001, Sep., 71 (3), pp. 404-7.

Paty D.W., Goodkin D., Thompson A., Rice G., Guidelines for Physicians with Patients on IFNB-1b: The Use of an Assay for Neutralizing Antibodies (NAB), Neurology, 1996, 47, pp. 865-866.

Petrella J.R., Grossman R. I., McGowan J.C., Campbell G., et al., Multiple Sclerosis Lesions: Relationship Between MR Enhancement Pattern and Magnetization Transfer Effect, American Journal of Neuroradiology, Jun-Jul 1996, 17 (6), pp. 1041-9.

Polman C.H., Thompson A.J., Murray T.J., McDonald W. I., Multiple Sclerosis, The Guide to Treatment and Management, fifth edition, Demos Medical Publishing, New York, 2001.

Polman C.H., Hartung H.P., The Treatment of Multiple Sclerosis: Current and Future, Current Opinion in Neurology, June 1995, 8 (3), pp. 200-9.

Poser C.M., The Epidemiology of Multiple Sclerosis: A General Overview [Review], Annals of Neurology, Dec. 1994, 36 Suppl. 2, pp. S180-93.

Poser C.M., Multiple Sclerosis. Observations and Reflections – A Personal Memoir, Journal of the Neurological Sciences, Feb. 1992, 107 (2), pp. 127-40.

Poser C.M., The Pathogenesis of Multiple Sclerosis, Journal of Neurological Sciences, Apr. 1993, 115 Suppl., pp. S3-15.

Poser C.M., The Role of Trauma in the Pathogenesis of Multiple Sclerosis: A Review, Clinical Neurology and Neurosurgery, May 1994, 96 (2), pp. 103-10.

Pozzilli C., Bastianello S., Koudriavtseva T., Gasperini C., et al., Magnetic Resonance Imaging Changes with Recombinant Human Interferon Beta-1a, Journal of Neurology, Neurosurgery and Psychiatry, Sep. 1996, 61 (3), pp. 251-8.

Prineus J.W., Barnard R.O., Kwon E.E., Sharer L.R., Cho E.S., Multiple Sclerosis: Remyelination of Nascent Lesions, Annals of Neurology, Feb. 1993, 33 (2), pp. 137-51.

Puri J., Arnon R., Gurevich E., Teitelbaum D., Modulation of the Immune Response in Multiple Sclerosis: Production of Monoclonal Antibodies Specific to HLA/Myelin Basic Protein, Journal of Immunology, Mar. 1, 1997, 158 (5) pp. 2471-6.

Quast U., Herder C., Zwisler O., Vaccination of Patients with Encephalomyelitis Disseminata, Vaccine, Apr. 1991, 9 (4), pp. 228-30.

Rabusin M., Andolina M., Aximova N., et al., Immunoablation followed by autologous hematopoietic stem cell infusion for the treatment of severe autoimmune disease, Haematologica, Nov. 2000, 85(11 Suppl), pp. 81-5.

Richert ND., Ostuni JL., Bash CN., et al., Interferon beta-1b and intravenous methylprednisolone promote lesion recovery in multiple sclerosis, Mult. Scler., Feb. 2001, 7(1), 49-58.

Ristori G., Buzzi M.G., Sabatini U., et al., Use of Bacille Calmette-Guerin (BCG) in multiple sclerosis, Neurology 1999, Oct. 22, 53 (7), pp. 1588-9.

Robertson N.P., Clayton D., Fraser M., Deans J., Compston D.A., Clinical Concordance in Sibling Pairs with Multiple Sclerosis, Neurology, Aug. 1996, 47 (2), pp. 347-52.

Rolak L.A., Multiple Sclerosis Treatment 2001, Neurologic Clinics, Volume 19 Number 1 Feb. 2001, pp 107-118. Rosner L., Ross S., Multiple Sclerosis, Fireside, New York, 1992.

Rosenberg G.A., Dencoff J.E., Correa N. Jr., Reiners M., et al., Effect of Steroids on CSF Matrix Metalloproteinases in Multiple Sclerosis: Relation to Blood-Brain Barrier Injury., Neurology, June 1996, 46 (6), pp. 1626-32.

Rudge P., Miller D., Crimlisk H., Thorpe J., Does Interferon Beta Cause Initial Exacerbation of Multiple Sclerosis?, Lancet, Mar. 4, 1995, 345 (8949), p. 580.

Rudick R.A., Antel J., Confavreux C., Cutter G., et al., Clinical Outcomes Assessment in Multiple Sclerosis, Annals of Neurology, Sept. 1996, 40 (3), pp. 469-79.

Rudick R.A., Goodkin D.E., Jacobs L.D., et al., Impact of Interferon Beta-1a on Neurologic Disability in Relapsing Multiple Sclerosis, Neurology, Aug. 1997, 49 (2), pp. 358-63.

Rudick R.A., Goodkin D.E., Ransohoff R.M., Pharmacotherapy of Multiple Sclerosis: Current Status [Review], Cleveland Clinic Journal of Medicine, May-June 1992, 59 (3), pp. 267-77.

Ruffini F., Furlan R., Poliani PL., et al., Fibroblast growth factor-II gene therapy reverts the clinical course and the pathological signs of chronic experimental autoimmune encephalomyelitis in C57BL/6 mice, Gene Ther., Aug. 2001, 8(16), pp. 1207-13.

Sadovnick A.D., Genetic Epidemiology of Multiple Sclerosis: A Survey [Review], Annals of Neurology, Dec. 1994, 36 Suppl. 2, pp. S194-203.

Sadovnick A.D., Ebers G.C., Genetics of Multiple Sclerosis, Neurologic Clinics, Feb. 1995, 13 (1), pp. 99-118.

Salmaggi A., Milanese C., Eoli M., La Mantia L., Nespolo A., Dufour A., Immunological Monitoring and Clinical Evaluation in Cyclophosphamide-Treated Progressive Multiple Sclerosis Patients, International Journal of Neuroscience, June 1994, 76 (3-4), pp. 305-12.

Sanders V.J., Waddell A.E., Felisan S.L., Li X., Conrad A.J., Tourtellotte W.W., Herpes Simplex Virus in Postmortem Multiple Sclerosis Brain Tissue, Archives of Neurology, Feb. 1996, 53 (2), pp. 125-33.

Schapiro R., Multiple Sclerosis, A Rehabilitation Approach to Management, Demos Publications, New York, 1991.

Schapiro R., Symptom Management in Multiple Sclerosis, Demos Publications, 1994.

Schwid S.R., Goodman A.D., Puzas J.E., McDermott M.P., et al., Sporadic Corticosteroid Pulses and Osteoporosis in Multiple Sclerosis, Archives of Neurology, Aug. 1996, 53 (8), pp. 753-7.

Sibley W., Therapeutic Claims in Multiple Sclerosis, 3rd edition, Demos Publications, 1992.

Sipe J.C., Romine J.S., Koziol J.A., McMillan R., Zyroff J., Beutler E., Cladribine in Treatment of Chronic Progressive Multiple Sclerosis, The Lancet, July 2, 1994, 344, pp. 9-13.

Sobel R.A., The Pathology of Multiple Sclerosis, Neurologic Clinics, Feb. 1995, 13 (1), pp. 1-21.

Sorensen P.S., Treatment of Multiple Sclerosis with IVIg: Potential Effects and Methodology of Clinical Trials, Journal of Neurology, Neurosurgery, and Psychiatry, Nov. 1994, 57 Suppl., pp. 62-4.

Sorensen P.S., Wanscher B., Szpirt W., Jensen C.V., et al., Plasma Exchange Combined with Azathioprine in Multiple Sclerosis Using Serial Gadolinium-Enhanced MRI to Monitor Disease Activity: A Randomized Single-Masked Cross-Over Pilot Study, Neurology, June 1996, 46 (6), pp. 1620-5.

Stinissen P., Zhang J., Medaer R., Vandevyver C., Raus J., Vaccination with Autoreactive T Cell Clones in Multiple Sclerosis: Overview of Immunological and Clinical Data, Journal of Neuroscience Research, Aug. 15, 1996, 45 (4), pp. 500-11.

Stone L.A., Frank J.A., Albert P.S., Bash C.N., et al., Characterization of MRI Response to Treatment With Interferon Beta-1b: Contrast-Enhancing MRI Lesion Frequency as a Primary Outcome Measure, Neurology, Sep. 1997, 49 (3), pp. 862-9.

Stone L.A., Frank J.A., Albert P.S., Bash C., Smith M.E., Maloni H., McFarland H.F., The Effect of Interferon-Beta on Blood-Brain Barrier Disruptions Demonstrated by Contrast-Enhanced Magnetic Resonance Imaging in Relapsing-Remitting Multiple Sclerosis, Annals of Neurology, May 1995, 37 (5), pp. 611-9.

Tenser R.B., Aberg J.A., Immunoglobulin G Immunosuppression of Multiple Sclerosis, Suppression of All Three Major Lymphocyte Subsets, Archives of Neurology, Apr. 1993, 50 (4), pp. 417-20.

Trapp B.D., Peterson J., Ransohoff R.M., Rudick R., et al., Axonal Transection in the Lesions of Multiple Sclerosis, The New England Journal of Medicine, Jan. 29, 1998, 338 (5), pp. 278-85.

Trobe J.D., High-Dose Corticosteroid Regimen Retards Development of Multiple Sclerosis in Optic Neuritis Treatment Trial, Archives of Ophthalmology, Jan. 1994, 112 (1), pp. 35-6.Tuohy V.K., Yu M., Weinstock-Guttman B., Kinkel R.P., Diversity and Plasticity of Self Recognition During the Development of Multiple Sclerosis, Journal of Clinical Investigation, Apr. 1, 1997, 99 (7), pp. 1682-90.

Turbridy N., Behan PO., Capiledo R., et al., The effect of anti-alpha4 integrin antibody on brain lesion activity in MS. The UK Antegren Study Group, Neurology, Aug. 1999, 53(3), pp. 444-5.

van Gelder M., Mulder A.H. van Bekkum D.W., Treatment of Relapsing Experimental Autoimmune Encephalomyelitis with Largely MHC-Matched Allogeneic Bone Marrow Transplantation, Transplantation, Sept. 27, 1996, 62 (6), pp. 810-8.

van den Noort S., Holland N.J., Multiple Sclerosis in Clinical Practice, Demos Medical Publishing, New York, 1999.

van Noort J.M., Multiple Sclerosis: An Altered Immune Response or an Altered Stress Response? [review], Journal of Molecular Medicine, June 1996, 74 (6), pp. 285-96.

van Noort J.M., van Sechel A.C., Bajramovic J.J., el Ouagmiri M., Polman C.H., Lassmann H., Ravid R., The Small Heat-Shock Protein Alpha B-Crystallin as Candidate Autoantigen in Multiple Sclerosis, Nature, June 29, 1995, 375 (6534), pp. 798-801.

van Oosten B.W., Lai M., Hodgkinson S., Barkhof F., et al., Treatment of Multiple Sclerosis with the Monoclonal Anti-CD4 Antibody cM-T412: Results of a Randomized, Double-Blind, Placebo-Controlled, MR-Monitored Phase II Trial, Neurology, Aug. 1997, 49 (2), pp. 351-7.

van Oosten B.W., Truyen L., Barkhof F., Polman C.H., Multiple Sclerosis Therapy. A Practical Guide [Review], Drugs, Feb. 1995, 49 (2), pp. 200-12.

Vandenbark A.A., Chou Y.K., Bourdette D.N., Whitham R., Hashim G.A., Offner H., T-Cell Receptor Peptide Therapy for Autoimmune Disease [Review], Apr. 1992, 5 Suppl. A, pp. 83-92.

Vandenbark A.A., Chou Y.K., Whitham R., Mass M., et al, Treatment of Multiple Sclerosis with T-Cell Receptor Peptides: Results of a Double-Blind Pilot Trial, Nature Medicine, Oct. 1, 1996, 2, pp. 1109-1115.

Voskuhl R.R., Palaszynski K., Sex hormones in experimental autoimmune encephalomyelitis: implications for multiple sclerosis, Neuroscientist 2001, June, 7 (3), pp. 258-70.

Warrington AE., Bieber AJ., Ciric B., et al., Immunoglobulin-mediated CNS repair, J. Allergy Clin. Immunol., Oct. 2001, 108(4 Suppl), S121-5.

Waxman SG, Demyelination in Spinal Cord Injury and Multiple Sclerosis: What Can We Do to Enhance Functional Recovery? Journal of Neurotrauma, 1992 Mar; 9 Suppl 1:S105-17.

Weiner H.L., Hohol M.J., Khoury S.J., Dawson D.M., Hafler D.A., Therapy for Multiple Sclerosis, Neurologic Clinics, Feb. 1995, 13 (1), pp. 173-96.

Weinshenker B.G., The Natural History of Multiple Sclerosis, Neurologic Clinics, Feb. 1995, 13 (1), pp. 119-46.

Weinshenker B.G., Issa M., Baskerville J., Meta-Analysis of the Placebo-Treated Groups in Clinical Trials of Progressive MS, Neurology, June 1996, 46 (6), pp. 1613-9.

Weinstock-Guttman B., Kinkel R.P., Cohen J.A., Ransohoff R.M., et al., Treatment of Fulminant Multiple Sclerosis with Intravenous Cyclophosphamide, The Neurologist, May 1997, 3 (3), pp. 178-85.

Wood D.D., Bilbao J.M., O’Connors P., Moscarello M.A., Acute Multiple Sclerosis (Marburg Type) is Associated with Developmentally Immature Myelin Basic Protein, Annals of Neurology, Jul. 1996, 40 (1), pp. 18-24.

Zhao G.J., Magnetic Resonance Imaging in the Evaluation of Clinical Trials in Multiple Sclerosis, Annals of Neurology, 1994, 36 Suppl, pp. 95-6.

Information also obtained from:

Associated Press, AutoImmune, Berlex Laboratories, Biogen Medical Research, Immunex, International Federation of Multiple Sclerosis Societies, The Myelin Project, Pharmaceutical Marketing Alliance, Reuters Health Information Services, Schering AG, Serono, Teva Neuroscience