What is Multiple Sclerosis (MS)?
Most scientists would describe MS as an autoimmune disease that
affects the central nervous system (CNS). Between 55,000 and 75,000
Canadians suffer from MS, the majority diagnosed between the ages of
20 and 50. Its clinical course is progressive yet unpredictable: it
can be mild, moderate or severe, have periods of remission and
relapse; in some people it is characterized by acute episodes and in
others continuous decline. It affects women more often than men,
those living in temperate climates more than tropical climates.
Canada has one of the highest rates of MS in the world.
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
affects the cell's myelin which conducts electrical impulses to and
from the brain. Eventually this inflammation creates scarring or
mylenation along the axon by laying down plaque or lesions.
The disruption in electrical impulse produces functional impairment -
the symptoms of MS - including difficulty with balance and walking,
blurred vision, urinary and sexual dysfunction, speech impairment and
cognitive or emotional problems; the scarring produces irreversible
damage to nerve fibers.
Current treatment
MS is usually treated with drugs that depress the immune response,
depending on the stage of the illness and its prognosis. While these
drugs often have the affect of slowing the disease or of preventing
or delaying an exacerbation of symptoms, once functionality has been
lost it is usually not recovered. 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.
Research directions
MS as a multi-factorial, autoimmune disease affecting the nervous
system has prompted research in many different directions: 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 MS, the research both borrows from and contributes to our
understanding of the mechanisms involved in all autoimmune diseases;
indicates treatments that could work for cancer and other diseases;
uses stem cells in ways that have not been tried before; and inspires
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.
Broadly speaking, MS research is concentrating on two questions: how
can the disease progression be arrested? Can the myelin be repaired
to restore neurological functioning once it has been lost? Stem
cells are helping to answer both of these questions.
Using Stem Cells to treat MS
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 poor prognosis.
In clinical trials at the University of Ottawa, scientists are using
autologous transplantation (a graft of the patient's own stem cells
that have been purified of immune cells) rather than allogeneic
transplantation (stem cells from a donor's bone marrow). They
believe that autologous HSCT will benefit patients with an autoimmune
disease caused by a strong environmental trigger, whereas allogeneic
transplantation would be more suitable for treating autoimmune
diseases with a strong genetic basis.
By completely destroying the patient's immune system through
chemotherapy (immunoablative therapy) and reintroducing stem cells
taken from the patient's bone marrow purified of immune cells, the
immune system can be reconstituted. 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. 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.
By following patients for several years after they had immunoablative
therapy - total obliteration of the immune system followed by HSCT -
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 selected patients who have aggressive
MS, resetting their illness to a more responsive stage. Phase I-II
trials of this treatment regimen are now underway in Montreal,
Toronto and Ottawa. As more patients undergo autologous stem cell
transplantation, scientist will better understand which patients can
benefit from this therapy with the least risk and side effects.
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.
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.
Brain repair and tissue regeneration
In order to address this question, cell biologists are trying to
determine how and why immune cells create and perpetuate the
autoimmune response and by what mechanism the demylenation 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 remylenation might occur, and the
possible role of drug therapy, gene therapy or stem cell therapy.
Whether stem cells are responsible for the functional improvement
seen in some MS patients who undergo HSCT, or whether they might be
used in treatments to enhance and encourage remylenation, is the
focus of research on mesenchymal stem cells (MSC). These are stem
cells derived from the bone marrow that are destined to become neural
cells and might be implanted directly into the brain to see if these
cells are capable of repairing the brain. Animal studies have shown
that when these cells are transplanted they migrate to where the
myelin has been damaged and differentiate into the cells which are
needed to create new myelin to protect the nerve fibers. 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.
Additional Resources
MS Society of Canada: http://www.mssociet
National MS Society: http://www.national
Glossary: www.mssociety.
MS Research in North America:
www.mssociety.
www.nationalmmsocie
www.nationalmssocie
http://www.stemcell
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StemCells subscribers may also be interested in these sites:
Children's Neurobiological Solutions
http://www.CNSfoundation.org/
Cord Blood Registry
http://www.CordBlood.com/at.cgi?a=150123
The CNS Healing Group
http://groups.yahoo.com/group/CNS_Healing
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