What is Multiple Sclerosis (MS)?

Symptoms and treatment
Importance of early treatment
Can stem cells help?
Halting disease progression
Brain repair and tissue regeneration
Looking to the future
General Information

Most scientists would describe multiple sclerosis (MS) as an autoimmune disease that affects the central nervous system (CNS). Multiple sclerosis typically has periods of remission and relapse, followed by progressive disability. The course is unpredictable with rapid progression in some people and infrequent episodes in others. The disabilities can be mild, moderate or severe.

MS affects women more often than men, those living in temperate climates more than tropical climates. Most people are diagnosed between the ages of 20 and 50.

There are probably both genetic factors that predispose someone to MS, as well as environmental factors that trigger the immune system to malfunction. In MS, immune cells attack the myelin sheath which protects nerve fibers (axons) in the brain and spinal cord, much like the insulation on an electrical wire.

The resulting inflammation causes demyelination along the axon which shortcircuits the electrical impulses that travel from the brain. Eventually, the inflammation can lead to destruction of the nerve fibers or axons, resulting in permanent disability.

Symptoms and treatments

The symptoms of MS are not specific but may affect many different abilities, including difficulty with balance and walking, trouble with coordination, numbness or ‘pins and needles,' blurred vision, urinary and sexual dysfunction, speech impairment and cognitive or emotional problems.

MS is usually treated with drugs that modulate the immune response, depending on the stage of the illness and its prognosis. These drugs often have the effect of slowing the disease or of preventing (or delaying) the exacerbation of symptoms. Scientists believe the disease returns because therapies have failed to change the immune response that gives rise to the CNS inflammation or to remove the immune ‘memory' that has learned to attack the myelin.

Importance of early treatment

Although immunoablative therapy appears to have arrested inflammation and prevented new lesions in the clinical trials mentioned above, it does not appear to have stemmed the progressive neurodegenerative aspects of MS that were already underway.

Scientists are concluding from these and other studies that early intervention (before significant disability) is critical in treating MS. Inflammation at an early stage of the disease leads to the eventual loss of axons and neurons. It is believed that at some point the disease undergoes a transition from primarily an inflammatory disease to a more progressive neurodegenerative disease.

This was confirmed in January 2009 in a study at Northwestern University in Chicago where immunoablation was done at an earlier stage in the disease. Of the 21 adults with relapsing-remitting MS who had stem cells transplanted from their own bone marrow, 17 showed improvement, none had a worsening of symptoms and 16 had no relapse after three years.

This was the first MS study of any treatment to show reversal of damage. Researchers believe this is an instance of the brain repairing itself; however, the therapeutic intervention must occur early. This approach is contrary to other studies where stem cell therapy has been tried as a treatment of last resort.

Can Stem Cells Help?

Multiple sclerosis, as a multi-factorial, autoimmune disease affecting the nervous system, has prompted research in several different specialties: cell biology, genetics, immunology and neuroscience. These streams of research are all in their own way trying to explain what triggers the disease, the wide variety of symptoms and the baffling course of progression. While the aim is ultimately to help those who suffer with the disease, the research into MS both borrows from, and contributes to, our understanding of the mechanisms involved in all autoimmune diseases.

Stem cell research into MS is developing new imaging technology and laboratory techniques that will help researchers understand what is really going on in the brain and in the genes that control the immune system. The lessons learned in treating MS might also be applicable in understanding and developing new treatments for other autoimmune diseases, such as rheumatoid arthritis, Crohn’s disease and lupus.

Broadly speaking, MS research is concentrating on two questions: how can the disease progression be arrested? Can the nervous system be repaired to restore neurological functioning once it has been lost? Stem cells are helping to answer both of these questions.

Halting disease progression

Stem cells have been used for years to treat leukemia and other blood cancers through transplantation of bone marrow. Scientists have found that the same process, known as hematopoietic stem cell transplantation (HSCT), can be adapted to arrest the progression of MS in patients who have an especially aggressive disease diagnosed early on and a poor prognosis.

There are two kinds of stem cell transplantation: autologous transplantation (a graft of the patient's own stem cells from the blood or bone marrow that have been purified of immune cells) and allogeneic transplantation (stem cells from a donor's bone marrow or bloodstream). In theory, autologous HSCT would benefit patients with an autoimmune disease caused by a strong environmental trigger, whereas allogeneic transplantation might be more suitable for treating autoimmune diseases with a strong genetic basis.

Ongoing clinical trials in Canada using autologous transplantation to treat MS are in effect testing this hypothesis. By completely destroying the patient's immune system through chemotherapy (immunoablative therapy) and reintroducing stem cells taken from the patient's own bone marrow or blood, the immune system can be reconstituted. When transplanted, the stem cells differentiate into all of the different types of blood cells, but they do not carry the immunologic memory of previous exposures to environmental triggers, making the reappearance of autoimmunity improbable.

Specialized care is required for patients undergoing the high doses of chemotherapy and transplantation because of the serious complications that could develop. To the degree that MS does not progress (new lesions are not created), it helps to prove the principle that MS is due to a learned immune response to an infectious or environmental agent rather than to a genetic predisposition.

Scientists are concluding from these and other studies that early intervention (before significant disability) is critical in treating MS since inflammation at an early stage of the disease leads to the eventual loss of axons and neurons. It is believed that at some point the disease undergoes a transition from primarily an inflammatory disease to a more progressive neurodegenerative disease.

Brain repair and tissue regeneration

In order to address the question of whether myelin that has already been destroyed by MS can be repaired, cell biologists are trying to determine how and why immune cells create and perpetuate the autoimmune response and by what mechanism the demyelination occurs. MS not only destroys myelin but it damages or kills the cells that make myelin (oligodentrocytes) and nerve cells. They are hoping to crack the cell signaling codes and interrupt the pathways that orchestrate destruction of the myelin sheath. This will help them understand under what conditions remyelination might occur, and the possible role of drug therapy, gene therapy or stem cell therapy.

Whether the transplanted stem cells are responsible for the functional improvement seen in some MS patients who undergo HSCT, or whether stopping inflammation may allow the brain to repair itself is unclear, but understanding these mechanisms might lead to treatments to enhance and encourage remyelination. This is the focus of research on mesenchymal stem cells. These are stem cells derived from the bone marrow that have immune-suppressing and regenerative properties and in theory may be capable of repairing the brain damaged by MS.

Scientists working on this aspect of MS say that "regenerating lost brain tissue is the next frontier in MS - to add repair to what we can already do to fight inflammation."

Looking to the future

Stem cell research for MS is progressing in Canada, the United States, the United Kingdom, Israel, Germany, Australia and Japan. Some researchers are concentrating on the autoimmune response, others are decoding the signals that prompt the brain to repair itself by forming new myelin when the original myelin has been destroyed. While the ultimate objective is to find a cure, current stem cell research is providing vital clues and making it possible in the foreseeable future to induce and prolong remission, or even alter the course of the disease.

Canada

Canada has one of the highest rates of MS in the world. The Multiple Sclerosis Society of Canada recently revised its estimates of the prevalence of MS in Canada from 50,000 in the 1980’s to between 55,000 and 75,000 in 2006. Prevalence rates vary significantly by region for unknown reasons, and while there is some evidence that the risk of MS is increasing, these numbers may also reflect improvements in diagnostic technology.

Scientists at the Ottawa Hospital Research Institute (OHRI) have demonstrated in early phase clinical trials that immunoablative therapy and autologous stem cell transplantation is effective for treatment of aggressive MS. By following patients for several years after they had immunoablative therapy, scientists found that the inflammatory process can be arrested, and new lesions are not formed. Further research will attempt to determine whether a lesser degree of immune ablation might still provide important benefits to those patients who have aggressive MS, resetting their illness to a more responsive stage.

Phase I-II trials of this treatment regimen continue in Montreal, Toronto and Ottawa. As more patients undergo autologous stem cell transplantation, scientists will better understand which patients can benefit from this therapy with the least risk and fewest side effects.

New technology is helping to track the progression of MS and the effectiveness of the therapeutic measures mentioned above. For example, a new MRI technique developed at the Montreal Neurological Institute can compare the areas of the brain that are remyelinating and the areas that are demyelinating.

Which is the best stem cell to use for transplantation? Researchers in Toronto and Saskatchewan are looking to the regenerative capacity of special cells found in human skin, inside the nose and in the spinal cord as autologous sources of myelinating cells. These precursor cells are multipotent, which means they can differentiate into many different kinds cells, including those that produce myelin. On the basis of successful experiments using rats, scientists are hopeful that these precursor cells can be harvested and transplanted for the treatment of neurological disease or injury.

For the Public

What is Multiple Sclerosis (MS)?

Symptoms and treatments

Importance of early treatment

Can Stem Cells Help?

Halting disease progression

Brain repair and tissue regeneration

Looking to the future

Canada

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