What are some promising new treatments for multiple sclerosis?

Treatments for Multiple Sclerosis

• I want a list of new treatments, including alternative treatments, for progressive relapsing/remitting multiple sclerosis

• Answer:

  Hello, jt1967! Thank you for your patience while I put this answer together. I wanted to make sure I covered the most recent research on treatments for Multiple Sclerosis so that I would avoid duplicating information you likely already know. Since MS has so many symptoms that can progress and worsen over time, many of the references may deal with only one or two symptoms. I have included some "cutting-edge" therapies that are still in the clinical stage. Finally, it was hard to restrict the search to just the "progressive relapsing/remitting" stage of MS, since many of these treatments are applicable through various stages of the disease. Although I am sure you are very familiar with resources concerning MS, a good overview of the stages, current treatments and the recent research is available in the following recorded interview from Healthtalk Interactive: "Symptom Management, Treatment Options and Research Updates." Guest: Anthony Reder, MD, Kevin McCoyd, MD, Joy Wagner, RN, BSN . (Recorded May 22, 2003) HealthTalk Interactive. http://www.healthtalk.com/msen/052203/052203.pdf ============================================== NEWER DRUG TREATMENTS/INVESTIGATIONS/THERAPIES ============================================== CAMPATH (ALEMTUZUMAB) TO SLOW DISEASE PROGRESSION AND REDUCE BRAIN INFLAMMATION ================================================================================ "Participants Sought At Multiple Sites For Clinical Trial Testing Campath® In Early, Active Relapsing-Remitting MS." National. Multiple Sclerosis Society Research Bulletins. (June 11, 2003) http://www.nationalmssociety.org/Research-2003June11.asp Summary: "Participants are being enrolled for a new clinical trial getting under way in the U.S. and Europe, testing the ability of CAMPATH®, an immune-suppressing monoclonal antibody also called alemtuzumab, to slow disease progression and reduce brain inflammation in early, active relapsing-remitting MS." "The primary objective of the study is to determine efficacy of CAMPATH compared with Rebif in slowing time to sustained accumulation of disability, frequency of relapses, and accumulation of brain lesions seen with MRI. Additional objectives are to determine comparative safety and tolerability." "Over the past decade, investigators at Cambridge University in the U.K. have used CAMPATH to treat MS, using a variety of doses and delivery schedules, and on different forms of MS. They have reported positive effects on brain lesions detected by MRI, on controlling immune function and on reducing disease relapses, and in some cases actually reversing disability. In spite of short-term worsening of MS symptoms upon initiation of CAMPATH (which is treated by pre-medication with steroids), and the development of thyroid disease in about 25-30% of treated patients (see "Safety Consideration," below), these early studies have encouraged the investigators to study CAMPATH more intensively in individuals with early, active MS to better determine its safety and efficacy in controlling inflammatory responses and hopefully slowing progression of disability." == "Early Use of Campath in MS May Decrease Disability," by Larry Schuster. Medscape Medical News.(April 3, 2003) http://www.medscape.com/viewarticle/451858 "Campath-1H (alemtuzumab) virtually stops episodes and decreases the disability of early-stage multiple sclerosis (MS), according to a small open-label study." "The effect is only seen when the drug, a humanized monoclonal antibody that depletes T cells, is given in the early relapsing-remitting stage of the disease, Alastair Compston, PhD, FRCP, chairman of the department of neurology, Cambridge University, U.K., told attendees of the American Academy of Neurology 55th annual meeting, "when clinical disease activity is attributable to inflammation." (Read More....) ENHANCING MEMORY WITH ARICEPT ============================= "ARICEPT® SHOWS POTENTIAL TO IMPROVE MEMORY IN MS." National. Multiple Sclerosis Society Research Bulletins. (April 4, 2003) http://www.nationalmssociety.org/Research-2003Apr4.asp Excerpt: Summary:"A new study showed that the oral medication Aricept® (donepezil hydrochloride, Pfizer, Inc.) modestly improved performance on a memory test in individuals with multiple sclerosis." "Researchers are investigating whether Aricept - a drug shown to improve memory in Alzheimer’s disease - can improve memory in MS. 35 subjects taking Aricept showed significantly greater improvements on a memory test, and according to clinician and patient reports, than 34 subjects taking placebo. Larger studies are needed to confirm the safety and benefits of this medication for improving memory in MS." Conclusions: "This study, although small, suggests that Aricept may have the potential to modestly improve memory function in individuals with MS who have mild to moderate cognitive impairment. However, it is not clear to what extent this improvement would have an impact on daily activities. Larger studies are needed to confirm the safety and benefits of this medication for improving memory in MS." ZOCOR MAY REDUCE NEW MRI-DETECTED BRAIN LESIONS =============================================== "EARLY STUDY FINDS ORAL CHOLESTEROL DRUG ZOCOR® SAFE FOR MS; LARGER STUDIES NEEDED." National Multiple Sclerosis Society Research Bulletins. (April 1, 2003) http://www.nationalmssociety.org/Research-2003Apr1.asp "Summary: A small clinical trial was done of the oral cholesterol-lowering drug Zocor® in 30 individuals with relapsing-remitting MS: "Zocor appeared to reduce the number of new MRI-detected brain lesions over the six-month treatment period, and demonstrated other signs of possible benefit; Previous studies have suggested that this and other statin drugs can alter immune responses in a way that may be beneficial for treating MS; Larger, controlled trials will be required to determine the drug’s safety and effectiveness against MS; such trials are in planning stages." Results:"Preliminary analysis of the results indicates a significant (43%) decrease in the mean number of new lesions, and in the volume of new lesions. No serious adverse events related to treatment occurred. Analysis of immune responses suggested a positive shift away from inflammation, but there were no differences observed in neurological status or disability in this short study." Conclusions: "This small study, indicating possible benefit on lesion development and immune activity, shows promising results for Zocor in treating people with relapsing-remitting MS." BETASERON FOR REDUCING RELAPSE RATE AND POTENTIAL REDUCTION OF BRAIN LESIONS ============================================================================ "FDA Extends Approval Of Betaseron® To "Relapsing Forms Of MS," Including Secondary-Progressive MS With Relapses." National Multiple Sclerosis Society Research Bulletins. (March 19, 2003) http://www.nationalmssociety.org/Research-2003Mar19.asp "..significant benefit with treatment was seen in several secondary outcomes, including reduced relapse rate and reduced steroid use for relapses. There was also reduced accumulation of new brain lesions and of persistent lesions detected by MRI." Conclusions: "The FDA’s approval of extending labeling of Betaseron to treat relapsing forms of MS means that individuals with secondary-progressive MS who experience relapses now have a new treatment option." == Also read "MS Study Explores Effects of Increasing Dose and Frequency of Beta Interferon Therapy." (March 17, 2003) http://www.betaseron.com/betas/rel2003/20030315.jsp AVONEX CAN DELAY THE ONSET OF A SECOND ATTACK ============================================= "FDA Extends Avonex® Labeling To Include Those Experiencing First Attack and Having MRI Suggestive of MS." National Multiple Sclerosis Society Research Bulletins. (February 7, 2003) http://www.nationalmssociety.org/Research-2003Feb7.asp Conclusions: "Research suggests that damage to brain and spinal cord tissues can occur early in the disease course of multiple sclerosis. These data show that use of Avonex after a single demyelinating attack in people with multiple brain lesions can delay onset of a second attack and thus of clinically definite MS. Thus, the FDA’s approval of expanded labeling of Avonex supports earliest treatment which many believe may forestall the development of permanent clinical disabilities. This is also a signal to physicians and third-party insurers that this is an appropriate treatment for individuals with this condition." POSSIBLE VIRAL CAUSE OF MS AND ANTIBIOTIC THERAPY ================================================== "Antibiotic treatment trial directed against C. pneumoniae in MS". Current Funded Research/Tennessee. National Multiple Sclerosis Society. http://www.nationalmssociety.org/Research-Sriram2.asp (Research funded through 2004) "In previous Society-funded research, Subramaniam Sriram, MD, has observed a possible association between Chlamydia pneumoniae (a bacterium that causes a mild form of pneumonia) and the development of MS. It has not been proven, however, whether this or any other bacterium or virus actually triggers the disease." "If therapies used for C. pneumoniae infection are effective in treating MS, this may help determine the role of this bacterium. Dr. Sriram is administering antibiotics used to treat C. pneumoniae to 20 people with relapsing-remitting MS. Two centers are involved in conducting the trial. A third center will analyze the results using magnetic resonance imaging (MRI), to determine if antibiotic therapy alters the development of lesions (areas of damage). The results will be compared with 20 people who are taking inactive placebo." "If Dr. Sriram finds antibiotics to have an influence on MS in this small study, his findings may lead to a larger and more definitive study of this treatment alternative. Further study may also clarify the role of C. pneumoniae in the development of MS." ANTEGREN MAY REDUCE RELAPSES ============================= "Promising Results Published From Clinical Trial Of Antegren In MS." National Multiple Sclerosis Society Research Bulletins. (January 2, 2003) http://www.nationalmssociety.org/Research-2003Jan2.asp Summary: 'Promising results from an early-phase clinical trial of the monoclonal antibody natalizumab (Antegren®; Biogen Inc., Cambridge MA and Elan Corporation, PLC, Dublin) in relapsing forms of MS were recently published: "Those treated with Antegren by monthly intravenous infusions for 6 months had fewer new 'enhancing' MRI lesions than those treated with placebo, and treated patients had fewer relapses. No benefit on progression of disability was detected in this short study. Antegren functions by blocking the adhesion of immune cells to blood vessels and can inhibit movement of immune cells from the bloodstream into the brain.' "Conclusion: This short-term clinical trial showed promising results for an agent that appears to have a highly specific - and different - mode of action than currently available treatments. This study demonstrates that targeting movement of immune cells into the central nervous system is a reasonable approach to treatment of MS." == From "Symptom Management, Treatment Options and Research Updates." Multiple Sclerosis Education Network. (May 22, 2003) http://www.healthtalk.com/msen/052203/07.html "The ongoing studies right now that I think are interesting [are on] a drug called Antegren. It's an antibody that binds to a special type of T cell which is a white blood cell that gets up into the brain and causes trouble in MS. These are the activated memory cells that have this protein on their surfaces. The antibody, which is the drug, binds to that protein and doesn't allow the cells to get up into the brain. [Medical editor’s note: Antegren, also called natalizumab, is a monoclonal antibody that binds with a specialized T cell in such a way as to prevent the migration of the T cell across what is called the blood-brain barrier. It is necessary for the T cells to migrate into the brain to produce the damage in MS.] CANNABIS MAY EASE SYMPTOMS AND SLOW DEGENERATIVE PROCESS ======================================================== Abstract - "Cannabinoids inhibit neurodegeneration in models of multiple sclerosis." Pryce G, Ahmed Z, Hankey DJ, Jackson SJ, Croxford JL, Pocock JM, Ledent C, Petzold A, Thompson AJ, Giovannoni G, Cuzner ML, Baker D. Brain (July 2003) http://brain.oupjournals.org/cgi/content/abstract/awg224v1 (full text article may be bought at http://brain.oupjournals.org/cgi/reprint/awg224v1 As shown in an animal model of MS: "Therefore, in addition to symptom management, cannabis may also slow the neurodegenerative processes that ultimately lead to chronic disability in multiple sclerosis and probably other diseases. PULSED ELECTROMAGNETIC THERAPY MAY HELP EASE SYMPTOMS ===================================================== "Effects of a pulsed electromagnetic therapy on multiple sclerosis fatigue and quality of life: a double-blind, placebo controlled trial," by Lappin MS, Lawrie FW, Richards TL, Kramer ED. Altern Ther Health Med. 2003 Jul-Aug;9(4):38-48. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12868251&dopt=Abstract Excerpt from Abstract: "This study is a follow-up to a placebo controlled pilot study in which multiple sclerosis (MS) patients exposed to weak, extremely low frequency pulsed electromagnetic fields showed significant improvements on a composite symptom measure." CONCLUSIONS: "Evidence from this randomized, double-bind, placebo controlled trial is consistent with results from smaller studies suggesting that exposure to pulsing, weak electromagnetic fields can alleviate symptoms of MS. The clinical effects were small, however, and need to be replicated. Additional research is also needed to examine the possibility that ambulatory patients and patients taking interferons for their MS may be most responsive to this kind of treatment. AN OVERVIEW OF SOME CURRENT TREATMENTS FOR VARIOUS STAGES OF MS =============================================================== From "Perfect Pitch: Fine-tuning the Management of Multiple Sclerosis" By Patricia K. Coyle, MD (March 31, 2003) http://www.medscape.com/viewarticle/447692_3 The following section of the article may be found at http://www.medscape.com/viewprogram/2201 Treatment of Secondary Progressive MS Without Relapse ===================================================== "Data to support treatment of patients with secondary progressive MS without relapses are mixed. The European study of IFN beta-1b found treatment to be quite effective in patients with secondary progressive MS, with or without relapses.[27] No other study has been as convincingly positive. The International MS Secondary Progressive Avonex Controlled Trial (IMPACT), using double-dose IM IFN beta-1a, documented a treatment effect on progression as measured by the MS functional composite (MSFC) (25-foot timed walk, 9-hole peg test, Paced Auditory Serial Addition Test [PASAT]), but not on the EDSS.[28] However, the only significant effect on the MSFC was in the 9-hole peg test component. Neither the North American IFN beta-1b study nor the SC IFN beta-1a Secondary Progressive Efficacy Clinical Trial of Recombinant IFN beta-1a in MS (SPECTRIMS) trial showed an effect on progression based on EDSS.[29,30] "Despite the discrepancies in the effect of treatment on EDSS progression, all the trials of treatments for secondary progressive MS have shown benefits in suppressing superimposed relapses, and on MRI (T2 lesion burden, Gd+ lesions) parameters. The only DMT approved for secondary progressive MS in the United States is the immunosuppressor mitoxantrone. Because of concerns about cardiotoxicity, this drug can only be used up to a lifetime maximum of 140 mg/m2 (about 11 doses). The pivotal mitoxantrone in MS (MIMS) trial entered 194 patients who had relapsing and secondary progressive MS with or without relapses, but participants were randomized to 1 of 3 treatment arms,[31] and thus, no statement about statistical significance of treatment is possible with regard to the group of patients with secondary progressive MS without relapses." Treatment of Primary Progressive MS =================================== "There is no proven treatment for primary progressive MS. The recent phase 3 trial of glatiramer acetate (GA), the PROMISE trial, did not find a treatment benefit on progression. Although the drug was well tolerated, neither placebo- nor GA-treated patients deteriorated at the rate predicted from natural history studies. Two phase 2 trials of IFN beta in primary progressive MS have proved disappointing; 1 suggested modest benefits on secondary outcomes, the other was almost uniformly negative.[32,33] An ongoing phase 2 trial of mitoxantrone has not yet reported any results." "Thus, based on available evidence, use of DMT cannot be endorsed for patients with either secondary progressive MS without relapses or those with primary progressive MS, who together may account for 25% of all patients with MS. At the same time, a case can be made for treatment benefit in patients who have secondary progressive MS with Gd+ activity on MRI, who have worsened by greater than 1 EDSS point in the previous 2 years, or who are temporally close to their relapsing phase. In addition, a benefit of DMT, especially over the long term, has not been disproven for primary progressive MS." References Cited: http://www.medscape.com/viewarticle/447692_9 OVERVIEW OF SOME "NOVEL TREATMENTS" FOR MS =========================================== The following information is from "Perfect Pitch: Fine-tuning the Management of Multiple Sclerosis" By Patricia K. Coyle, MD (March 31, 2003) http://www.medscape.com/viewprogram/2201 The following excerpts may be found at http://www.medscape.com/viewarticle/447692_7 NATALIZUMAB: "Natalizumab, a humanized monoclonal antibody directed against alpha 4 integrins, blocks lymphocyte binding to endothelium and cell migration into the CNS. There are 2 ongoing phase 3 trials in relapsing MS." BONE MARROW TRANSPLANTATION: "At least 3 different groups are evaluating bone marrow transplantation to treat severe MS. Radiation and chemotherapy are used to ablate the host immune system, and then stem cells are infused to reconstitute a new healthy immune system. To minimize morbidity and mortality rates, autologous stem cells from the MS patient are harvested before treatment and later infused back. Although in theory allogenic healthy control stem cells are preferable, they involve the risk of graft vs host disease, with greater morbidity and mortality. Even autologous bone marrow transplantation carries a risk of death. To be considered successful, transplantation will have to stabilize patients for very prolonged periods and provide much better results than intensive drug immunosuppression." STATIN DRUGS MINOCYCLINE: "Another attractive, well-tolerated oral agent is minocycline. This oxytetracycline also has a number of immune effects that would be expected to benefit MS, including inhibition of matrix metalloproteinases, inducible nitric oxide synthase, caspases, tumor necrosis factor, and microglial activation, as well as induction of T helper 1 to T helper 2 immune deviation. Minocycline treatment lessens clinical and pathologic severity of EAE, with less CNS inflammation, demyelination, and microglial activation.[44] Preliminary studies are ongoing in relapsing MS." SEX HORMONES "Sex hormones are another novel treatment strategy. The most studied in connection with MS are the estrogens. In a single-center safety trial, oral estriol at 8 mg daily was well tolerated (menstrual cycle disruption was the only notable side effect) and appeared to benefit 6 women with relapsing MS. While on treatment, they showed reduced numbers and volume of contrast brain MRI lesions and stable T2 lesion volume. When taken off treatment, MRI activity increased, only to decrease again when estriol was reinstituted.[45] A phase 2 multicenter trial is planned." PPAR LIGANDS: Peroxisome proliferation-activated receptors (PPARs) are nuclear hormone receptors that regulate adipocyte differentiation and gene transcription. There are alpha, delta, and gamma isotypes. Oral PPAR ligands are being evaluated for treatment of diabetes. These drugs have multiple actions, including anti-inflammatory microglial effects, inhibition of T-cell activation and proliferation, and enhancement of myelin gene expression.[46] The PPAR ligand pioglitazone, as well as other PPAR ligands, have been shown to prevent or reduce severity of EAE. GLUTAMATE RECEPTOR ANTAGONISTS: "A number of studies suggest that glutamate excitotoxicity is a damage mechanism in MS.[47] In a recent report, riluzole treatment decreased development of cervical spinal cord atrophy and brain T1 hypointense lesions in patients with primary progressive MS.[48] Riluzole and other glutamate receptor antagonists may have a role in treating MS, but further studies are needed to confirm this role." CNS REPAIR: "CNS repair strategies are growing as a therapeutic focus, because they can theoretically restore function and improve fixed damage. As noted, many approaches are under development. One approach is to use neurotrophic factors to boost remyelination, preserve or restore neurons and oligodendrocytes, and protect or regenerate axons. Both ciliary neurotrophic factor and leukemia inhibitory factor can alleviate EAE. They may be helpful to promote oligodendrocyte survival in patients with MS." STEROIDS: "Recent studies suggest that glucocorticoids may have an impact on the MS disease process. In a single-center phase 2 trial, patients with relapsing MS were randomized to either receive regular pulses of intravenous steroids or only be treated at the time of relapse. At 5 years, the pulse steroid-treated patients showed less disability, brain atrophy, and T1 brain lesion load compared with those in the control group, who received steroids only for acute relapses.[49] Another small study evaluated brain lesions detected on monthly MRI scans of 4 patients with relapsing MS. Lesions showed the least permanent tissue damage (as measured by magnetic transfer ratio) when patients were treated with steroids.[50] The greatest tissue damage was noted in untreated lesions, while moderate damage was noted in lesions that occurred in IFN beta-treated patients. However, because complications involved with long-term steroid use may be significant, the role of steroids in management of MS needs further study, in terms of both safety and efficacy." http://www.medscape.com/viewarticle/447692_8 References Cited: http://www.medscape.com/viewarticle/447692_9 == Also Read: "In Search of Better Therapies for MS." by Rohit Bakshi, MD (April 2003) http://www.medscape.com/viewarticle/453292 "Corticosteroids or ACTH for acute exacerbations in multiple sclerosis," by Filippini G, Brusaferri F, Sibley WA, Citterio A, Ciucci G, Midgard R, Candelise L. From Cochrane Review Abstracts (Posted 04/01/2003) http://www.medscape.com/viewarticle/454353 "Natalizumab Useful in Autoimmune Disease," by Laurie Barclay, MD. Medscape Medical News. (Jan. 2, 2003) http://www.medscape.com/viewarticle/447304 ) "Statin Appears Promising for MS," by Larry Schuster. Medscape Medical News. (April 2, 2003) http://www.medscape.com/viewarticle/451781 STEM CELLS ========== Several MEDLINE Abstracts are available under the following reference: Stem Cell Transplants for Multiple Sclerosis. From Medscape Neurology & Neurosurgery (Posted 10/29/2002) http://www.medscape.com/viewarticle/441708 "Hematopoietic Stem Cell Transplantation for Multiple Sclerosis: A Retrospective Multicenter Study", by Fassas AS, Passweg JR, Anagnostopoulos A, et al. J Neurol. 2002;249:1088-1097 http://www.medscape.com/viewarticle/441708 Patients: "Eighty-five patients with progressive MS were treated with autologous HSCT in 20 centers and reported to the autoimmune disease working party of the European Group for Blood and Marrow Transplantation (EBMT)." Results: "The stem cell source was bone marrow in 6 and peripheral blood in 79, and stem cells were mobilized into peripheral blood using either cyclophosphamide combined with growth factors or growth factors alone. Three patients experienced transient neurological complications during the mobilization phase. The high dose regimen included combination chemotherapy, with or without anti-lymphocyte antibodies or, with or without, total body irradiation. The stem cell transplants were purged of lymphocytes in 52 patients. Median follow-up was 16 [3-59] months. There were 7 deaths, 5 due to toxicity and infectious complications, 2 with neurological deterioration. The risk of death of any cause at 3 years was 10 (+/-7)% (95 % confidence interval). Neurological deterioration during transplant was observed in 22 patients; this was transient in most but was associated with MS progression in 6 patients. Neurological improvement by >/= 1 point in the EDSS score was seen in 18 (21 %) patients. Confirmed progression-free survival was 74 (+/-12)% at 3 years being 66 (+/-23)% in patients with primary progressive MS but higher in patients with secondary progressive or relapsing-remitting MS, 78 (+/-13)%; p = 0.59. The probability of confirmed disease progression was 20 (+/-11)%. MRI data were available in 78 patients before transplant showing disease activity (gadolinium enhancing, new or enlarging lesions) in 33 %. Posttransplant MRI showed activity at any time in 5/61 (8 %) evaluable cases." Conclusion: "Autologous HSCT suggest positive early results in the management of progressive MS and is feasible. These multicentre data suggest an association with significant mortality risks especially in some patient groups and are being utilised in the planning of future trials to reduce transplant related mortality." === A QUESTION AND ANSWER ===================== From "Suggested Management of a Patient With Secondary Progressive Multiple Sclerosis." From Medscape Neurology & Neurosurgery. (Posted 05/13/2003) http://www.medscape.com/viewarticle/453702 Question (from Dr. Sharfuddin, United Kingdom) "What management strategy would you suggest for a patient with secondary progressive multiple sclerosis (SPMS) with clinical relapses and gadolinium-enhanced brainstem and cerebellar lesions on MRI? The clinical deficits are mild -- with Kurtzke Expanded Disability Status Scale (EDSS) of 2 and cardiomyopathy with good left ventricular function. She is on interferon beta-1a, 44 micrograms 3 times a week. Response from Mark S. Freedman, MD, 05/13/2003: "The diagnosis of SPMS in this patient might be a bit of a problem, as patients with this form of multiple sclerosis (MS) usually do not present with "mild" deficits. Most SPMS patients would, by definition, have progressed, usually in motor/cerebellar functions, to an EDSS of 3.5 or greater -- the minimum inclusion criterion for all SPMS studies." "More likely, this patient has relapsing remitting multiple sclerosis but is not experiencing complete recovery from relapses. Hence it appears that she is "progressing." It is not easy at times to discern "progression" from the accumulated deficits of relapses, especially early on." "Patients do not respond to interferons for many reasons. If the patient has been treated with an interferon for at least 6 months and continues to suffer relapses and multiple enhancing lesions, then it would appear that she is not responding well. She could be a poor responder or a poor healer. She also might have developed neutralizing antibodies to interferon (these can be measured). Finally, she might have a poor prognosis with accumulated disease that presents a larger burden than the routine disease-modifying drugs can handle." "So, in escalating beyond the disease-modifying drugs, one would consider mitoxantrone for this patient. Because of the patient's cardiac condition and the cardiac toxicities possible with this agent, however, its use would likely be contraindicated, but a cardiologist's opinion should be sought before therapy with mitoxantrone is ruled out." "The alternative would be to use another immunosuppressive regimen. Before the availability of mitoxantrone, we used the Harvard regimen with great success. The regimen consists of 1 g of intravenous methylprednisolone daily for 5 days; on day 4 the first dose of cyclophosphamide is added, at 800 mg/m2. For the first year, the regimen of 1 g methylprednisolone together with cyclophosphamide is given every 4 weeks, with the cyclophosphamide dose adjusted to produce a white blood cell count nadir of ~1.5 x 109/L. It is rare to increase the cyclophosphamide dose above 1400 mg/m2. In the second year this regimen is administered every 6 weeks, and then every 8 weeks the third year. By the end of the third year, maximal doses of cyclophosphamide will have been reached. This regimen is detailed in published reports.[1]" ALTERNATIVE THERAPIES TO HELP "EASE THE SYMPTOMS" OF MS ======================================================= The following natural therapies are not new but may help to ease the symptoms of multiple sclerosis for certain individuals. From "Multiple sclerosis and alternative therapies." Disability Online. Last reviewed: 30/06/2002 http://www.disability.vic.gov.au/dsonline/dsarticles.nsf/pages/Multiple_sclerosis_and_alternative_therapies?OpenDocument Excerpts: Acupuncture: "Acupuncture can help ease MS-related pain and reduce the severity of muscle spasms." Massage "Regular massages can help a person with MS to better manage muscle pain." Yoga: "Yoga can help relieve stress, because concentrating on the postures and breathing acts as a powerful form of meditation. The gentle sustained stretches also help to improve flexibility and reduce muscle stiffness." Chiropractic: "Back pain is a common problem for people with MS, exacerbated by weakened leg muscles. Chiropractic practice is recognised as one of the most effective treatments for back pain and injury." Meditation: "Meditation is a powerful stress management therapy." Evening primrose oil and fish oil supplements: "Some studies suggest that evening primrose oil and fish oil supplements can measurably reduce the severity and length of an MS attack. However, these supplements don't seem to influence the frequency of attacks." Dubious therapies: "The following alternative therapies, which are alleged to help people with MS, have been shown through clinical testing to be ineffective: Replacing mercury dental fillings - "Mercury in dental fillings has been incorrectly blamed for causing MS. This claim was made because mercury poisoning affects the brain and can cause symptoms similar to MS, such as muscle tremors." Hyperbaric oxygen therapy - "This means inhaling oxygen under pressure. Studies around the world have found that hyperbaric oxygen therapy has no effect on either MS symptoms or disease progression." Vitamin supplements - "High doses of vitamin or mineral supplements have no demonstrable influence on MS." Special diets - "There is no evidence that dietary factors contribute to the development of MS. Like anyone else, a person with MS should eat a well-balanced high fibre, low fat diet that includes fresh fruits, vegetables, cereals, lean meats and dairy products." === The Rocky Mountain MS Center at http://www.ms-cam.org/CAMbanner.htm has an entire site devoted to alternative therapies that may help with MS. You can subscribe for free and look through all the alternatives listed on the left column. A SCIENTIFIC REVIEW OF SELECT ALTERNATIVE THERAPIES =================================================== "Complementary and alternative therapies for treating multiple sclerosis symptoms: a systematic review," by Huntley A, Ernst E. Department of Complementary Medicine, School of Postgraduate Medicine and Health Sciences, University of Exeter, Exeter, UK. Complement Ther Med. 2000 Jun;8(2):97-105. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=10859602 Abstract: "Multiple sclerosis (MS) is a chronic disease of the central nervous system without a known cure. Thus the role of complementary and alternative therapies (CATs) for the management of symptoms lies in palliative care and this is borne out by the popularity of these treatments amongst MS sufferers.This review is aimed at determining whether this use is supported by evidence of effectiveness from rigorous clinical trials. Database literature searches were performed and papers were extracted in a pre-defined manner.Twelve randomized controlled trials were located that investigated a CAT for MS: nutritional therapy (4), massage (1), Feldenkrais bodywork (1), reflexology (1), magnetic field therapy (2), neural therapy (1) and psychological counselling (2).The evidence is not compelling for any of these therapies, with many trials suffering from significant methodological flaws. There is evidence to suggest some benefit of nutritional therapy for the physical symptoms of MS. Magnetic field therapy and neural therapy appear to have a short-term beneficial effect on the physical symptoms of MS. Massage/bodywork and psychological counselling seem to improve depression, anxiety and self-esteem. The effectiveness for other CATs is unproven at this time. In all the CATs examined further investigations are needed in the form of rigorous large-scale trials." === A website recommendation: One very comprehensive website that may be of interest to you, which seems to have everything all in "one place" is the Noah Website at http://www.noah-health.org/english/illness/neuro/muscler.html == A book recommendation: "Alternative Medicine and Multiple Sclerosis," by Allen C. Bowling, M.D.,Ph.D. Read a review on the Demos Medical Publishing website: http://www.demosmedpub.com/book88.html == I hope the information I have provided is helpful and provides some interesting resources. If you need further clarification, please do not hesitate to ask and I will be happy to help if I can! umiat-ga Google Search Strategy progressive relapsing remitting multiple sclerosis AND innovative treatments +alternative +therapies for "multiple sclerosis" PubMed Search http://www.ncbi.nih.gov/entrez/query.fcgi Multiple Sclerosis Multiple Sclerosis therapy Medscape Search http://www.medscape.com/medscapetodayhome Multiple Sclerosis