Milestones in the search for a cure

Strychnine and laxatives, antibiotics and vitamins, X-rays and steroids for the suppression of damaging immune reactions: Since Jean-Martin Charcot described MS for the first time as an independent disease in 1868 there have been a great many attempts to research and treat the illness. MS has many faces and it is also characterised by the fact that its symptoms can spontaneously go into remission: This makes it difficult to find therapies which really help. The history of the research and treatment of MS demonstrates how important it is to place research on a comprehensive and reliable data basis in future. Charcot initially experimented with the drugs which were then available for the treatment of neurological problems – for example auric chloride, zinc sulphate, strychnine and electro-stimulation, and later with belladonna, ergot and hydrotherapy. In the 1890s, MS was considered to be a consequence of overexertion and hysteria – patients were ordered complete bed rest and electro-stimulation.

The first vain therapy attempts

At the beginning of the 20th century it was speculated that MS symptoms were caused by a poison or metabolic anomaly. This led to therapy experiments with laxatives and stimulants and even tonsil operations were carried out. Since that time there have been scientific hypotheses which connect MS with infections and immune reactions - an assumption upon which the latest research is also based. Around 1920, patients were often treated with syphilis medication, regular injections of typhus vaccine, antibiotics and blood transfusions. In the 1930s and 1940s, physicians speculated that MS was caused by bad circulation in the brain and blood clots. As a consequence, therapies involving, for example, anticoagulants were applied.

History

During the 1950s and 1960s it was allergies which were considered to be the villains. Treatment was concentrated on antihistamines, vitamins and steroids taken within the context of various different diets. Since the seventies, research has assumed that MS is an auto-immune reaction which is possibly triggered by one or more infectious agents. On this assumption, the first tests were conducted involving the suppression of the immune system with drugs and X-rays. At the present time, treatment of MS is concentrating on reducing damaging immune reactions using steroids and other drugs. Worldwide, more than 100 clinical studies are currently testing potential MS therapies. The Ian McDonald MS Database of the Sylvia Lawry Centre records and evaluates almost all available data deriving from MS studies. These statistical profiles makes it possible to assess the efficacy of new therapies much more quickly and a great deal more cheaply: A milestone in the treatment of multiple sclerosis.

Research, studies, therapies - the chronology

1421		The first documented MS case: Saint Lidwina of Schiedam.
1868		First correlation of clinical MS symptoms with pathology of the central nervous system. The disease is designated by Jean-Martin Charcot as "sclérose en plaques".
1878		The role of myelin in nerve conduction is discovered by Louise Ranvier.
1916		First detailed microscopic description of tissue properties in a lesion of the central nervous system in diseased brain tissue by James Dawson.
1928		Discovery that myelin is formed by glia cells of the oligodendrocytes.
Before 1935		around 30 "therapies" for MS had been tried out, including some anti-infection and antiinflammatory drugs, as well as physical manipulations, psychiatric treatments and "alternative" therapy methods without unequivocal justification. Controlled studies which document a benefit vis-à-vis placebos are not yet carried out.
1933		"Acute experimental allergic encephalomyelitis" (EAE) is developed as model for MS.
1935		Discovery by Thomas Rivers of a veterinary disease which is similar to MS. In the final analysis, this indicates an auto-immune factor in the disease, whereby myelin is attacked in the central nervous system.
1937		MS is diagnosed using sensitivity to temperature: "The hot-bath test".
1948-49		First indications of raised antibody values in the fluid of MS patients. Determination that EAE is caused by immune problems in the lymphocytes. Elvin Kabat and others discover oligoclonal bands in the spinal fluid. As a result, a diagnostic test is available which indicates MS and establishes a connection with a disease of the immune system.
1935-1950		The attempts at treatment of MS concentrate on improving circulation (vasodilative agents, anticoagulants, circulation stimulants), vitamin therapy; anti-allergenic therapies and diets and physical manipulation (electrical stimulation of the spinal cord, massage, radicotomy). None of these treatments was carried out in the context of controlled studies; a clear benefit could not be determined.
1952		Discovery that EAE can be suppressed by anti-inflammatory and immunosuppressive drugs.
1953		First investigations of myelin decay in MS lesions.
1954-55		First precise and defined diagnostic criteria for MS (clinical and according to laboratory figures) and development of quantitative methods for classifying the disability.
1950s		Discovery that viruses are involved in many neurological diseases.
1963-65		Discovery of factors in blood which are toxic vis-à-vis myelin and which block nerve signals at the synapsis.
1964		First electron-microscope examination of MS lesions.
1969		Completion of the first controlled clinical studies on intramuscular ACTH in acute MS attacks; they demonstrate faster recovery from attacks than without ACTH. This is the first carefully controlled study of a successful therapy for MS using standardised diagnostic criteria and assessment scales for MS patients.
before 1970		Therapies addressing circulation and metabolic processes are tested and abandoned; various diets proposed, of which none shows any benefit. First treatment attempts for MS using immunosuppression via drugs and X-rays.
1972		First use of visual recording and otherwise elicited potentials for the support of MS diagnosis.
1978		Use of computer tomography to image MS lesions in living patients.
1979		Development of a model of EAE illustrating chronic and intermittent progress using genetically modified and easy-to-use mouse stems; determination of the important role of the immuno-regulatory system in this MS model.
1981		First magnetic resonance tomography studies (MRI) in myelin formation. The invention of MRI revolutionises the diagnosis of MS, and further research with this method have since led to the speculation that MS is sooner a permanently active disease rather than a relapsing one.
1981		Consensus on the significant role of placebo-controlled clinical double-blind studies for new therapeutic trials for new therapeutic agents in MS.
1982		MRI is used for the first time to image lesions in living patients.
1984		Use of MRI for identifying clinically silent lesions in MS patients.
1988		Using MRI, first proof that there is substantial lesion activity in the brains of MS patients, even when the disease is clinically silent.
1988		First use of magnetic resonance spectroscopy for monitoring chemical changes over time in individual MS lesions.
1989		Initials attempts to carry out MRI annually or more frequently in order to monitor the efficacy of new MS drugs.
1980s		Execution of a large number of precisely defined clinical trials in pilot or concluding studies, e.g.: Copolymer-I pilot study for intermittently progressing disease (possible effect identified); Copolymer-I studies for the chronically progressive disease (no effect); Cyclosporin A (slight effect with substantial toxicity); Alpha- and Beta-Interferon (possible effect; studies are still in progress); 4-Aminopyridin and 3,4-Diaminopyridin (possible effect in terms of improvement of symptoms); use of oral myelin to increase tolerance (possible effect).
1990-92		First valid studies on life expectancy and mortality factors in the case of MS.
1992		Berlex Laboratories applies to the FDA for a licence to market an Interferon Beta-1-b product for relapsing/remitting MS. The licence is granted in 1993. Betaseron/Betaferon is the first new drug to influence the disease cause since ACTH at the end of the sixties.
1993-2002		Avonex, Copaxon, Rebif and Novantron, the "general disease-modifying therapies", are licensed for the treatment of MS after Betaseron/Betaferon in Europe, America and worldwide.
more		Information about the history of MS can be found here