Neurology 2001 Oct 9;57(7):1239-47
by: www.clinicaltrials.gov 
Archives of Neurology
by: Janet E. Joy and Richard B. Johnson, Jr., Editors
Institute Of Medicine - National Acedemy Press, 2001
British Medical Journal
52nd Annual Meeting of the American Academy of Neurology
by: Rohit Bakshi, MD
by: Polman and Uitdehaag
BMJ ;321:490-494 August 19, 2000
by: Elliot M. Frohman, MD, PhD; Michael Racke, MD; Stanley van den Noort, MD
by: Dina A. Jacobs, MD; Steven L. Galetta, MD
Stephen Reingold PhD
Vice President Research and Medical Programs
National Multiple Sclerosis Society (USA)
Accepted treatments for MS are few and largely confined to speeding recovery from acute attacks of disease, or to managing symptoms.
For over 20 years, AdrenoCorticoTrophic Hormone (ACTH), and more recently Oral and Intravenous Steroids, have been used to help a person in an acute attack recover more rapidly than would occur spontaneously.
While neither safe nor effective for long-term chronic use, such medications are a major part of short-term treatment of Multiple Sclerosis attacks.
Symptomatic treatments are widely used for MS: Baclofen (Lioresal) is used world-wide to help control spasticity, and a new antispastic agents such as Tizanidine (Zanaflex) in Europe and the US are being developed as well.
Fatigue is often treated with some success with Amantadine (Symmetrel), Pemoline (Cylert) or other agents.
A number of medications are used to combat Bladder and Bowel difficulties, helping to avoid Urinary Tract Infections and provide better management of these functions.
Some of the more troubling symptoms of MS, however, have proven difficult to treat: Tremors are rarely effectively treated and Cognitive problems have not yet found any means of treatment other than attempts at counseling and Cognitive retraining.
Experimental treatments for MS are based largely on concepts developed after decades of intense basic and applied research, which has established in most scientists minds that MS is a disease of Immune regulation.
Most likely AutoImmune, with complex Genetic predisposing factors, triggered by unidentified infectious agent(s), and resulting in inflammation and breakdown of White Matter (Myelin) in the Brain and Spinal Cord.
These driving hypotheses in MS have led to current clinical research on agents that we hope will control the MS Immune Response, combat infectious agents that may trigger exacerbations, and improve the conduction of Nerve Fibers where Myelin has been damaged or lost.
Independent of the type of agent that is tested, clinical trials in MS are aimed at one or more therapeutic objective:
In reality, it is likely that no one therapy will accomplish all of these goals, and, while prevention and cure are the ultimate goals, success in any of the other goals has a significant impact on lives of people with MS.
In 1994 there are dozens of well designed clinical studies underway around the world aimed at finding new, safe and effective treatments; more than ever before in history, building on years of basic and applied research.
To alter disease course and ultimately stop progression, Immune regulatory drugs are being widely explored.
In the last decade, numerous *global* ImmunoSuppressive drugs like Cytoxan, Imuran, and Cyclosporine have been used, some widely, in an attempt to slow or stop disease progression.
Results have been ambiguous at best, however, and toxicity is high, since some of these agents turn off all Immune function and leave a person susceptible to Cancers and potentially fatal opportunistic Infections.
Exciting new experimental studies focus on more specific Immune therapies, using MonoClonal AntiBodies against specific Immune cells or to prevent movement of Immune cells from the Blood to the Central Nervous System.
Or, lab produced peptides that will target only those Immune functions relating to MS, leaving the rest of the Immune System functioning normally.
Other more traditional Immunoregulatory agents and techniques, such as Methotrexate, Mitoxantrone, Sulphasalizine, and others are being investigated as well.
Several agents are being tested in definitive trials now to reduce frequency of acute attacks or relapses.
Interferon-ß-1b (Betaseron) was approved by the US Food and Drug Administration in mid 1993 for use in early stage Relapsing/Remitting MS, where it was shown to reduce frequency and severity of relapses and reduce accumulation of MRI - detected lesions in the Brain.
Interferon-ß-1b and ß-1a (Avonex) - and the synthetic compound Copaxone (Copolymer-1) are under investigation at centers in the US and abroad to determine the effectiveness and safety of their use.
In addition to being a significant help to people with MS on a day to day basis, it is projected that reduction in number of acute attacks, may, over period of years, also result in less disease progression and fewer accumulated disabilities.
Knowledge of how loss of Myelin can affect nerve signal function in the CNS has led to the development of agents that may enhance nerve conduction, even with Myelin damage.
Current studies on 4Aminopyridine (4 AP) and 3,4 DiAminoPyridine (3,4 DAP) are targeted to determine the degree of clinically important functional improvement obtained with a medication dose that is safe.
Clinical studies of new drugs to definitively show benefit and safety in MS are time-consuming, extraordinarily detailed and extremely expensive.
Safety must be demonstrated, benefit must be proven, and the agent must be shown to be useful for a large number of patients being tested at multiple clinical centers.
There are many possible drugs that may be used to target one or more aspect of MS, and now, more than ever, they are being tested at centers throughout the world.