Goals of MS Treatment

Since multiple sclerosis was first classified as a unique disease nearly a century and a half ago, the situation has greatly changed. Treatment strategies have changed. But the ultimate goal has remained the same: to bring an end to multiple sclerosis.

Although multiple sclerosis was first classified as a unique disease more than 160 years ago, the next hundred years was marked by failed experimental therapies and radical treatments aimed at shortening relapses and arresting the disease.

For nearly a hundred years, people seemed willing to try almost anything. Yet with little understanding of the disease or what caused it, doctors and their patients were left to a frustrating pattern of trial and error. Toward the turn of the 20^th century, the possibility of MS being a toxin was raised. Early treatments rationalized by these theories included tonics; potions; and metal therapies of the day, such as arsenic and silver nitrate - despite a lack of clinical proof of any lasting effect on relapses or progression. Plasma and blood transfusions, even leeches, were tried as beliefs in the origin shifted between infection and toxin.

Desperate, doctors tried more radical, almost unthinkable measures. Electric shock therapy, pyrexia (also called "fever therapy", induced by malaria or typhoid vaccine), even organ transplants were attempted in vain1. Fed up and frustrated, once cooperative patients had finally had enough.

By the early 20^th century, theories of toxin involvement were largely being abandoned. With them, to the relief of many patients and doctors alike, went many of the radical and unproven measures of previous decades.

The Treatment Era

Since its discovery, there have been three central goals for treating multiple sclerosis and improving quality of life that have remained constant:

• Controlling relapses
• Managing symptoms
• Altering the course of the disease

The theory was simple. Understand why relapses occur and why they go into remission, and we can begin to find ways to control them. Discover the reasons why a particular set of symptoms would appear or persist, and we can formulate strategies to manage them. Understand what causes a disease and why it follows a particular course and we can discover ways to alter that course - and possibly one day reverse it.

Treatment Evolution

While the cause of MS is still unknown, much has been learned since the 1960's, when understanding the disease became a central goal of its own. Speculation over possible viral origins of multiple sclerosis has led to some discussions over the possibility of an MS vaccine - a theory balanced by equal speculation as to potential responses this could set off in the immune system of a person with MS.

Still, a fair amount of research is being conducted to understand the role one or more viruses may play in MS, and whether or not prevention may one day be an attainable treatment goal.

In the 1960's, steroids were introduced onto the treatment scene, bringing with them an enormous popularity that has kept them in favor to this day. As in previous decades, this "new" medical approach of the time was applied to treatments in multiple sclerosis.

Despite the excitement behind this new form of therapy, results did little to support their continued use. High doses of methylprednisolone were introduced in the 1980's and remain in the arsenal of several doctors to this day, though side effects and certain long-term concerns persist.

Signs Point toward Autoimmunity

Today's thought leaders in multiple sclerosis generally agree that, while MS is not a virus that can be "caught" by anyone who comes in contact with it, it is possible that a type of viral infection may trigger an autoimmune response that activates MS in people genetically predisposed to the disease.

The intense focus on immunologic treatments in MS is based on this theory of autoimmunity, which is supported by a number of factors observed in multiple sclerosis characteristic of other autoimmune disorders:

• The age of onset: A genetic predisposition with a delayed onset of the disease is also established in autoimmune disorders
• A predominance in women: With a few notable exceptions, most autoimmune disorders appear with greater prevalence in women rather than in men.
• Improvements during pregnancy: As with other autoimmune diseases, MS improves favorably during pregnancy.
• Relapses with remissions and A defined clinical course: Both relapses and remissions and a clinical course of the disease are characteristics that have been observed in other established immune disorders, including systemic lupus or rheumatoid arthritis.
• Cell activity: The way cells in the immune system react in MS has led researchers to conclude that an autoimmune attack does occur, though what causes these attacks remains unknown.

• Favourable response to immunotherapy: Clearly with the introduction of immunotherapy in the past few decades, evidence of beneficial responses has been observed, further supporting the autoimmune theory.

  Immunotherapy is arguably one of the most promising frontiers of today's medicine. The 1980's are often dubbed "the treatment decade" in MS, in part because of the tremendous amount of clinical trials under way during those years, a notable part of which includes the progress made toward immunomodulatory therapies.

  There are two types of treatments that affect the body's immune system:

• Immunomodulators: These treatments modify or regulate one or more immune functions, leaving the rest of the immune system operational.
• Immunosuppressants: As the name indicates, these therapies suppress multiple functions within the body's immune system.

Immunomodulatory therapies are those which have the ability to modify or regulate one or more functions of the immune system. The primary roles of these therapies are to control relapses and modify the course of MS. Their goal is to modify the immune system in an effort to control the immune-related chain of events associated with demyelination.

More specific benefits unique to different kinds of immunomodulators may also be achieved. The most preferable and logical immunomodulatory therapy would be one which is antigen specific. This means it would control only those actions in the immune system directly related to disease activity, leaving the rest of the body's immune functions operational to protect against colds, infection, contagious diseases and viruses like the flu.

Antigens are naturally occurring proteins in the body that activate the immune system. In MS, antigens are believed to activate the autoimmune response responsible for demyelination, which is why targeting these specific antigens is a goal of newer kinds of immunomodulatory treatments.

Immunosuppressants, on the other hand, have a more system-wide effect on the body's natural immune responses, bringing down not only what specific functions may be involved in the disease process but other regular immune functions as well. Cancer chemotherapy is an example of how immunosuppressants differ from more "specific" immunomodulatory treatments. Recent strides in other autoimmune disorders, such as cancer and AIDS, are largely attributed to immunologic advancements and treatments.

New Generation, New Goals

As the clinical course of multiple sclerosis begins to reveal itself, particular processes along the way also begin to unfold. These processes serve not only as a marker for the progression of MS, but as distinct points at which science can interrupt the disease itself.

Great strides have been made in the last decade toward uncovering these processes. With these discoveries come new theories to their particular roles in the demyelination and progression of MS - and new goals for treatments.

Axons are the part of the nerve cells that carry signals throughout the nervous system. If an axon is damaged, signals can't get where they're supposed to go. While no treatment or surgery has been proven to reverse axonal damage, this discovery has led to widespread support of early intervention with immunomodulatory treatments.

Prevention of axonal damage is certainly a goal. But how is this goal measured? In fact, in a disease marked by natural remissions, how is any goal attributed to a specific treatment?