Washington University neurologist
Anne Cross, MD
, remembers a
very different world when she
first began treating patients with multiplesclerosis (MS)
almost three decades ago.
“It’s incredible—the MS Center has
changed so much,” says Cross, director of
the John L. Trotter Multiple Sclerosis Center
at Barnes-Jewish Hospital. “During the first
10 years, we had no treatments that were
effective at slowing multiple sclerosis.
Now we have an array of treatments either
already in use, in clinical trials or on their
There are so many new options
Physicians normally group patients
into one of four clinical subtypes to help
anticipate the effects of MS and which
medications may work: relapsing remitting,
secondary progressive, primary progressive
and progressive relapsing. However,
the unpredictability of MS continues to
frustrate. The way patients respond to
the new treatments, which have varied
mechanisms of action, may provide
scientists with a much more accurate sense
of what’s going wrong in the different forms
of MS and in individual patients. That
knowledge could lead to better, more targeted
treatment and improved prognosis.
Current Standard of Care
Current medications offer some benefit
for certain MS patients but fall short of
controlling the disease. For relapsing
remitting MS, the most common form,
doctors often prescribe beta-interferons or
glatiramer acetate. But they must be taken
as injections and can cause adverse side
effects, including injection-site reactions
and a flu-like illness. These factors may
explain why up to 50 percent of MS patients
treated with the drugs fail to regularly take
Additional oral medications are
becoming available for relapsing MS
; they reduce the relapse rate by
about 30 percent to 50 percent, but there
is controversy over their ability to reduce
long-term disability. For secondary
progressive MS and primary progressive
MS, no treatments have proved to be
effective at reducing progressive disability.
The latest MS pharmaceutical treatment
approved by the FDA is teriflunomide, a
compound that blocks rapid white blood
—a key component of
the autoimmune processes that cause MS.
Teriflunomide is among the first MS drugs that
can be administered orally via a daily tablet.
Another daily tablet, fingolimod, won
FDA approval in 2010
. It traps immune
lymphocytes that contribute to MS inside
the lymph glands where they develop and
is effective for relapsing forms of MS.
A multicenter trial called INFORM is
ongoing to study whether fingolimod will
also be effective as a treatment for primary
progressive MS. Neurologist Becky Parks,MD
, co-director of the MS Center, is leading
that study at Washington University and
“There’s also evidence that fingolimod
crosses the blood-brain barrier and enters the brain and spinal cord,” Cross says. “We
think that may be helpful in MS because
fingolimod can bind to SIP receptors in
the brain, which leads to an increase in
neurotrophic factors, at least in mice.”
Fingolimod is now available at the
MS Center as a treatment for relapsing
forms of MS.
In addition to the INFORM trial,
Washington University neurologists at the
center are currently participating in three
clinical trials of new monoclonal antibodies
designed for MS treatment.
- Robert Naismith, MD, is leading OPERA,
an assessment of the benefits and risks of
treating relapsing remitting patients with
a beta-interferon versus ocrelizumab, an
antibody that depletes immune B cells.
- Anne Cross, MD, is principal investigator
for a second ocrelizumab trial,
ORATORIO. This study is testing whether
ocrelizumab will slow or stop neurologic
progression in patients with primary
- Becky Parks, MD, is leading the center’s
study of daclizumab, an antibody that
increases CD56+ natural killer T cells.
Striving for Tailored Treatment
Cross notes that the alterations some of
the newest MS treatments cause in the
immune system could produce vulnerability
to infection. She says physicians have to
strike a careful balance between the benefits
of new MS treatments and potential risks,
some of which are not yet well-characterized.
“The challenging aspect of having all
these new drugs is that now we have a lot
of different options to weigh,” Cross says.
“We desperately need ways to determine
which patients will do better on which drugs
to help with these clinical decisions.”
To meet this need, Cross and colleagues
Sheng-Kwei Song, PhD, and Dmitriy
Yablonskiy, PhD, are developing new
imaging techniques to better characterize
what happens in the brains of MS patients
before, during and after treatment.
Genetics may also provide clues.
Laura Piccio, MD, Washington University
neurologist at Barnes-Jewish Hospital, is
working with the National MS Genetics
Consortium to determine whether differences
in patients’ DNA can help doctors identify
the best treatments for those patients.
“Many MS specialists think we now
need to alter our goals for MS therapy and
set our sights higher, aiming for freedom
from disease activity altogether. That means
no MS flare-ups, disability progression or
disease activity seen on MRI scans,” Cross
says. “We cannot do that for everyone with
MS yet, but it’s becoming an increasingly
feasible goal for the future.”