Summary
- Researchers
in Canada have published results of a long-term trial of an individuals’
own (autologous) hematopoietic (blood cell-producing) stem cell
transplantation. The study involved 24 people with aggressive
relapsing-remitting MS whose disease was not controlled with available
therapies.
- Three
years after the procedure, 70% remained free of disease activity, with no
relapses, no new MRI-detected inflammatory brain lesions, and no signs of
progression.
- None of
the surviving participants, who were followed for 4 to 13 years after the
procedure, experienced clinical relapses or required MS disease-modifying
therapies to control their disease, and 40% experienced reductions in
disability.
- One of
the participants died and another required intensive hospital care for
liver complications. All participants developed fevers, which were
frequently associated with infections, and other toxicities.
- Additional
research is focusing on figuring out who might benefit from this procedure
and how to reduce its risks.
“These results suggest that
aggressive MS may be stopped with an effective but risky procedure, for a
subset of people,” said Dr. Bruce Bebo, Executive Vice President, Research, at
the National MS Society. “Additional research by investigators around the world
is focusing on figuring out who might benefit from this procedure and how to
reduce its risks, which can include death.”
Details
Background: An experimental procedure that has been explored for several
years in MS is called “autologous hematopoietic (blood cell-producing) stem
cell transplantation” – or HSCT. This procedure has been used in attempts to
“reboot” the immune system, which launches attacks on the brain and spinal cord
in people with MS.
In HSCT, the stem cells (derived from a person’s own bone marrow or blood) are
stored, and the rest of the individual’s immune cells are depleted by
chemotherapy. Then the stored stem cells are reintroduced by infusion into the
vein. The new stem cells migrate to the bone marrow and over time produce new
blood cells, including immune cells. The goal of this currently experimental
procedure is to establish a new immune system that no longer recognizes myelin
and other nervous system tissue as dangerous. In theory, this should stop the
attacks that lead to tissue damage and disability.
There are a number of laboratories around the world testing variations of HSCT
for the treatment of autoimmune diseases, including MS. Preliminary findings
suggest this is a promising, but potentially risky strategy for the treatment
of MS.
The Study: Drs. Harold Atkins, Mark Freedman and team at the Ottawa
Hospital, University of Ottawa and other institutions in Canada conducted a
Phase 2 trial of HSCT that involved 24 people with aggressive
relapsing-remitting MS whose disease was not controlled with available
therapies. No control group was used which would have enabled comparison
against the results found in the treatment group. The procedure used by this
group included complete destruction of bone marrow cells and an additional step
that enriched the transplanted cells for stem cells.
Results - Safety: One of the participants died of
transplantation-related complications that caused liver failure and another
required intensive hospital care for liver complications. The treatment regimen
was modified over the course of the study to reduce toxicity, but all
participants still developed fevers, which were frequently associated with
infections.
Results – Effectiveness: Three years after the procedure, 70% of the
participants remained free of disease activity, meaning they had no relapses,
no new MRI-detected inflammatory brain lesions, and no signs of progression.
The remaining 30% experienced progression of disability. In addition, for the
entire follow-up period ranging from 4 to 13 years after the procedure, of the
23 survivors:
- None
experienced clinical relapse, had new active inflammatory MRI brain
lesions, or required MS disease-modifying therapies to control their
disease.
- The
average rate of brain atrophy (shrinkage), a measure that has been linked
to MS progression, returned to levels associated with normal aging.
- 40
percent experienced some lasting reversal of disability such as vision
loss, muscle weakness and balance problems.
- Some
were able to return to work or school.
The results were published online on June 9, 2016 in
The Lancet. Major funding for the study came from the MS
Society of Canada and its affiliated Multiple Sclerosis Scientific Research
Foundation.
Next Steps: Rigorous clinical trials of stem cell therapies are needed
to determine their safety and effectiveness in people with MS. Trials of this
and other stem cell therapy approaches are taking place in Canada, the United
States, Europe and elsewhere. To help explore the potential of stem cell
therapy, in November 2015, the International Conference on Cell-Based
Therapy for Multiple Sclerosis was convened in Lisbon, Portugal under the
auspices of the International Advisory Committee on Clinical Trials in MS (a
group jointly sponsored by the National MS Society and the European Committee
for Treatment and Research in Multiple Sclerosis). Seventy leading researchers
and clinicians conferred on clinical trials needed to provide answers about
which types of cells, which route of delivery, and which types and stages of
disease, would be the most promising approach for treating MS. Read more about this meeting
Read more about stem cells and MS
