Research time line

Research time line – multiple sclerosis

While MS has been identified as a disease for more than 120 years, for most of those years, MS therapy was based on hunches–without controlled trials that measure effectiveness. And people with MS were subjected to hopelessly ineffective treatments–such as tonsil extraction.

Today, while many questions remain to be answered, MS research has been set free by new biotechnology. Treatments under study are no longer shots in the dark. They have a rationale, supported by painstakingly acquired science on how the human body works at its most fundamental level. Four fields–where knowledge has exploded in the past two decades–are yielding important treatment ideas.

* Cell biology Knowledge of the nature of oligodendrocyte cells is building. These central nervous system cells manufacture myelin, the material that is damaged in MS.

* Genetics More than one gene governs susceptibility to MS. The search for these genes is now in progress.

* Immunology Immune reactions appear to be responsible for damage to myelin in MS. How the immune system works in MS is still unfolding…but ways to intervene are now possible.

* Virology A triggering agent has long been suspected in MS. Techniques for finding and identifying virus are now easier and faster than ever before.

1860s to 1910s

SCIENTIFIC UNDERSTANDING

* Microscope used to identify myelin, the nerve fiber insulating material (1860) Scientists learn to grow cells in lab dishes (1910s)

* Laws of genetics, ignored in 1850s, re-examined (1900) Term gone first used (1909)

* First clues to how body fights infection: antibodies found (1889)

* Existence of viruses established (1900s)

* Clinical Care

MS described as a distinct disease (1860)

Tonics and stimulants given, including: gold chloride, zinc sulfate, silver nitrate, strychnine, ergot, belladonna, electricity, hydrotherapy

No lasting benefits, no controlled studies

1920s to 1940s

SCIENTIFIC UNDERSTANDING

* Oligodendrocytes (0Iigo’s)identified as source of myelin (1928)

Nerve fibers that have lost myelin conduct nerve impulses poorly (1937)

* Lab animals are inbred to create strains susceptible to specific diseases (1933)

* Experimental Allergic Encephalomyelitis (or EAE), an MS-like disease, is caused by stimulating immune response to myelin–in inbred animals

Lymphocytes (white blood cells) have role in the immune response (1936)

Antibodies are made by lymphocytes called B-cells ‘

* A virus that infects oligodendrocyte cells of sheep and causes myelin damage is found

* Clinical Care

More 30 different treatments are tried, including: tonsil extraction, x-rays, anti-allergy injections, vasodilators and anticoagulants (to increase blood flow), psychiatry, massage, vitamins, special diets

No lasting benefits, no controlled studies

1950s to 1970s

SCIENTIFIC UNDERSTANDING

* Sodium and potassium ions found essential to nerve conduction (1950)

Tools of molecular and cellular biology developed, providing unprecedented windows into life on the cellular level

* Structure of DNA revealed (1953) Family susceptibility to MS described Genes found to control “self” and “non-self” recognition (1975)

* Immune cells called T-cells react against myelin (1965)

Immune cells that “suppress” or “help” immune reactions found

Monoclonalantibodies made in lab to seek and identity specific T-cell types (1976)

Immune reactions are regulated through cytokines, made by immune cells. They include the interferons.

Blood-brain barrier stops immune cells from entering central nervous system (CNS) (1956) Adhesion molecules involved when immune cells cross this barrier (1977)

* Search for a “triggering” virus begins (1972)

* Clinical Care

Science moves into the MS clinic

First scales to measure disability developed

First CT scans “see” MS lesions

First prevalence studies, showing gender bias and latitude effects

Study shows people with MS have higher than normal levels of antibodies against viruses

Era of controlled clinical trials in MS begins in 1960s. Early results include:

* Anti-inflammatory hormone ACTH speeds recovery from acute attacks (1969)

* Copolymer I–a synthetic look-a-like of myelin basic protein–“promising” in first pilot trial (1979)

1980s to 1990s

SCIENTIFIC UNDERSTANDING

* Brain cells called astrocytes found to cause scar tissue in MS; search for agents to block scarring begins (1980)

Oglio cells can produce new myelin in adults; work to stimulate new myelin begins (1981)

Oglio cell growth factors identified (1986) Myelin is successfully transplanted from one animal to another (1989)

* Search for MS susceptibility genes: studies of twins and MS families begin (1989); studies using fast new PCR technology begin (1991)

* Roles of the interferons in regulating immune response clarified (1989)

T-cell subsets that react against myelin tentatively identified (1991)

Monoclonal antibodies to adhesion molecules created; they stop immune ceils from crossing blood-brain barrier, which prevents EAE in lab animals (1992)

* Molecular mimicry theory explains how a virus could cause immune cells to attack the body’s own myelin (1984)

* Clinical Care

Ideas for therapy now stem directly from new science. Many treatments prove safe enough and promising enough in lab and animal studies to test with people.

Proven treatments now control many symptoms. Many other treatments are in early clinical trials. Control of MS sought. Pilot trials are asking:

* Can antibodies that block adhesion molecules stop immune activity in the human central nervous system?

* Can antibodies against myelin (or protein fragments called peptides) block anti-myelin T-cells?

* Can oral myelin components impede or eliminate anti-myelin T-cells?

Large multi-centertrials, in progress now, are due to yield definitive results:

Beta interferon–to control relapses

Copolymer I–to control relapses

4AP–to improve nerve conduction

Before 1960, at least forty-three reports described positive results in MS treatment. But the improvements turned out to be indistinguishable from changes that would have occurred without treatment.

MS “comes and goes”—a phenomenon that has deceived many well-meaning researchers. Without controlled clinical trials, physicians treated MS with the “theory of the day” electricity in the 1860’s, psychiatry in the 1930’s, drugs to increase blood flow in the early 1950’s.

In 1981, MS specialists formally agreed that double-blind, controlled clinical trials are the “gold standard” measurement of the effectiveness of therapies for MS.

Today, demonstrated therapies help mange symptoms such as spasticity, pain, urinary or bowel problems, and fatigue-and moderate or shorten exacerbations. Tomorrow, scientists are hopeful that treatments will be found to slow or stop the course of this formidable disorder.

Please note: The examples shown on these pages are illustrations–not a definitive list of achievements, and our dates are approximations reflecting the fact that scientific discoveries are actually acquired slowly over time, and always involve contributions from the past.

COPYRIGHT 1993 National Multiple Sclerosis Society

COPYRIGHT 2004 Gale Group