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Can Bone Marrow Transplantation
Help Patients With Multiple Sclerosis?
Maybe. That's what several teams of researchers in the US and
Europe are now trying to determine.
Multiple sclerosis is an autoimmune disease that attacks the
central nervous system. In patients with MS, the immune system malfunctions and
destroys myelin. Myelin is a mixture of lipids (fat) and protein that surrounds
and insulates nerves.
The exact cause of MS is unclear. Several studies suggest that
exposure to an environmental agent, possibly a virus, triggers the immune
system to malfunction in persons who have a genetic predisposition to
developing the disease. Some researchers believe MS develops 7 to 10 years
after exposure to the environmental agent.
Of the 300,000 persons in the US living with MS, most are women.
Patients are usually diagnosed between the ages of 20 and 40.
Symptoms of MS may be mild, such as numbness or weakness in the
limbs, blurred vision, clumsiness, or severe, such as paralysis, loss of
intellect and blindness. Approximately 70 percent of patients experience
symptoms only sporadically. Their life expectancy is similar to that of the
general population, although they may live with disabilities such as decreased
vision, numbness, loss of balance, incontinence of stool or urine, weakness or
loss of function of arms or legs. Some may need to use a cane or
wheelchair.
In other patients the disease progresses rapidly, severely
impairing organ function and quality of life. Patients with rapidly progressing
disease are usually bedridden, confined to a wheelchair or dead within 10
years,
Many of the symptoms and the pain associated with MS can be
managed with drugs and physical therapy. Agents that suppress the immune system
such as cyclophosphamide or prednisone have also been helpful in slowing the
progression of the disease. However, no currently available therapy cures MS.
Because the life expectancy and quality of life of patients
diagnosed with rapidly progressing MS is so poor, researchers are now studying
whether high dose chemotherapy, with or without radiation, followed by a bone
marrow or stem cell transplant can cure patients who have MS, or extend and
improve their quality of life.
Treatment of autoimmune disorders with bone marrow transplantation
(BMT) is not new. BMT has been the standard treatment for severe aplastic
anemia for many years. Other autoimmune diseases such as thalassemia and
Fanconi anemia have also been successfully treated with BMT.
Animals infected with a disease similar to MS have shown
improvement or been cured following BMT. Additionally, at least one patient who
had MS and underwent BMT to treat another disease, showed improvement in MS
symptoms following the transplant.
Richard K. Burt, one of the investigators studying whether BMT is
a promising treatment for MS, has treated six MS patients with BMT to date.
"Our first patient was a 43-year old molecular biologist who had
been functioning well until age 40," Burt told a national symposium in December
1997. "Three years after her diagnosis, she was in a wheelchair, barely able to
get out of it without help, and had severe tremors. She was incontinent, unable
to feed herself and could no longer read. Thirteen months after being treated
with BMT, she was again able to read and authored a paper about her experience
with MS."
Of the six patients treated with BMT, three have shown improvement
and three have had no further progression of their disease. Thus far, says
Burt, all patients have remained off immunosuppressive drugs. He cautions,
however, that it will be many years before researchers can reliably assess
whether BMT provides long-term benefits for MS patients.
Type of Transplant
MS may be treated by one of two types of BMT: allogeneic BMT or
autologous BMT. In allogeneic BMT, bone marrow from a donor is transplanted
into the patient. In autologous BMT, the patient's own bone marrow is used
during the transplant.
Bone marrow is rich in stem cells—the cells from which all
blood cells evolve. Following high dose chemotherapy and radiation, a patient's
bone marrow is destroyed. Until new stem cells are infused or transplanted into
the patient and begin producing new blood cells, the patient is at risk of
developing life-threatening infections and excessive bleeding.
Although bone marrow has the highest concentration of stem cells
in the body, stem cells can be moved from the bone marrow to the circulating
blood by drugs called cytokines. The stem cells may then be collected from the
circulating blood and used instead of, or in addition to, bone marrow.
Transplants that use stem cells collected in this manner are called peripheral
blood stem cell transplants.
It is not yet clear which type of transplant is best for treating
MS. Each has its own advantages and disadvantages.
Theoretically, an allogeneic transplant is more likely to cure a
patient than an autologous transplant, since disease-free marrow from a donor
is used. However, the treatment risks, including death, associated with
allogeneic BMT are significantly higher than those associated with autologous
BMT. Since MS patients with advanced disease often already have significant
central nervous system damage, they may be less likely to withstand the rigors
of allogeneic BMT than patients who undergo allogeneic BMT to treat a different
disease.
Although autologous BMT is less toxic than allogeneic BMT, there
is the risk that the patient will be reinfused with marrow that contains MS
cells that could cause the disease to recur. To overcome this problem some
researchers "purge" autologous bone marrow or peripheral blood stem cells prior
to reinfusing them into the patient, in an effort to remove as many diseased
cells as possible. Whether or not purging will provide any long term benefit
for MS patients is not yet clear.
Other Diseases Under Study
In addition to MS, the treatment of three other autoimmune
disorders with BMT is currently under investigation. Patients at high risk of
early mortality from rheumatoid arthritis, systemic lupus erythematosus or
systemic sclerosis are considered candidates for BMT at several transplant
centers in the US. Although early results are encouraging, too few patients
have been treated and follow-up has been too short to determine the value of
BMT in treating these diseases at this time. |
