- [Narrator] So, you know, we're doing a lot of research,
as are other laboratories,
trying to better understand multiple sclerosis.
We've been categorizing, lumping patients
into relapsing-remitting
or primary progressive or secondary progressive,
but we think that the disease is much more varied
and that even different types of inflammation
could be involved in one person versus the other.
We use a mouse model in which we induce an MS-like syndrome
by deliberately provoking an immune response
against the myelin sheath.
And these mice succumb to a syndrome which looks like MS.
In fact, they have relapses and remissions like patients do.
And we, several years ago, published our findings
that we could induce this MS-like disease
with different types of inflammatory cells,
but it looked the same in terms of
the type of deficits the mice developed.
And here we also saw different patterns
in terms of the inflammation.
This is a spinal cord of a mouse with the MS-like disease.
And right here, these dark areas,
indicate inflammatory cells,
and you could see there, at the edge of the spinal cord.
The other type of MS we induced
with other types of inflammatory cells had the infiltrates
or inflammation which extended deeper
into the spinal cord tissue, seen here.
And there were different types of white blood cells
that were producing different types of toxic factors.
So this paper actually got a lot of attention
because it suggests that perhaps among individuals with MS,
there may be different triggers
and different types of damage being done.
And that may explain why some patients respond
to one drug rather than another.
For example, some patients may have good control
of their disease with Copaxone
but not beta interferons like Avonex or Rebif.
In other patients it may be the reverse.
Why is that?
Well, we believe it's because these patients
have different types of inflammatory damage
that respond differently to single agents.
And as we understand the types
of inflammation better and better,
we hope one day to customize therapies
that fit an individual and stop the disease effectively.
So we've also begun looking at the immune response
in patients with multiple sclerosis.
We've been collecting blood from some patients
on a monthly basis over the course of a year,
and we've been analyzing whether there are
inflammatory cells producing toxic factors.
And this is just to show you
that we see different patterns in different individuals.
So compared to healthy individuals,
there's a lot more activity in the blood of the MS patients.
But these open circles and closed,
I'm sorry, these closed circles and open squares
represents different types of inflammation,
different types of factors
that are being produced by the blood cells.
And in one group of patients, we see more of the factor
that corresponds to the open squares.
In another group of patients, we see more of the factors
that correlate with these closed circles.
And then in other patients, it's more of a mixed pattern.
So we're beginning to understand how the immune system
could be abnormal in different ways between individuals,
and maybe we could use this information
to develop better drugs that are more suited
to the type of inflammation someone has.
How much time do I have, David?
Five minutes?
Okay, so I will just quickly go through
the last part of the talk, in which I wanted to
concentrate a little bit on the secondary progressive form
of MS, because that's the form of MS,
also primary progressive MS,
for which we have the least treatments.
And this is a patient of mine
who came to me at the age of 38.
In the year 2000, he had tingling in his fingertips.
His hands and his legs were weak.
He had bladder control issues.
And he also had that Lhermitte's sign.
When he bent his neck down,
he got that electric shock sensation down his back.
So this meant that he had some damage
in the spinal cord in the neck.
But he recovered from that.
Four years later, he noticed that he would drag
his right foot after exertion, for example, mowing the lawn.
And then the next year, he had a very discrete episode
of gait imbalance, double vision, and vertigo.
At that point, his doctors ordered MRI scans
and a spinal tap, leading to the diagnosis of
multiple sclerosis.
And he was started on a drug called Copaxone.
So this is a typical relapsing-remitting pattern.
He had these discrete lesions,
which were particularly bad over a time period.
He recovered from them.
And then four years later or a year later,
he developed a new set of symptoms.
He eventually developed optic neuritis,
cloudy vision in the left eye.
But then starting in 2008, he had a more gradual
accumulation of deficits, in that his gait got
more and more labored.
He had some weakness in raising his right leg and fatigue,
some difficulties with short-term memory,
but these were very slowly evolving.
He couldn't actually pinpoint a particular week
or a month when they started or got worse.
And he started using a cane by 2009.
So this is an illustration of someone
who had the relapsing-remitting disease
and then went into secondary progression.
Now, we have some very effective drugs
to stop the relapsing-remitting disease
or to suppress it significantly,
and the drugs are getting better and better
and more and more effective.
And today the outlook for patients with
relapsing-remitting disease, if they're diagnosed early,
is much brighter than it was in the past.
But we haven't made as much progress
when patients enter this progressive phase.
We're hopeful that patients who are treated
with these new generations of drugs
that are better at suppressing relapses
may delay their entry into progression or even prevent it.
Time will tell because those drugs haven't been around
long enough for us really to be able
to draw definitive conclusions.
But for patients who are already in this stage,
we're trying to focus more and more research
on understanding it better and developing
more effective drugs.
And the last thing I wanted to say is
in terms of some of the research we're doing.
It turns out that in the progressive phase,
patients don't respond well to the Copaxone
and beta interferons that worked earlier on.
And people say, well, that's 'cause there's
less inflammation.
But there is a subset of patients we're finding
with progressive disease who do have inflammation.
And in fact, this is the MRI scan
on the individual I told you about earlier.
And when we added the gadolinium,
he actually did active inflammation around the plaque,
even though he was in the progressive phase of disease.
The patients who have this inflammatory type of activity
in the progressive phase, you could only capture them
by doing multiple MRI scans and studies
'cause the inflammation is less frequent.
But we found in our study and some other clinical trials
have found that if you do multiple MRI scans,
for example, monthly or every other month
for three to six months, you'll find about 30%
of patients with progressive disease will have
some evidence of inflammation.
And it turns out, it's beginning to look like
that percentage of patients may respond better
to the drugs that work in relapsing-remitting disease,
as opposed to patients who don't have any
inflammatory activity, which is still the majority.
But if we can pinpoint the group of patients
who do have some inflammation going on,
we may be able to more effectively treat them,
as long as we could identify them.
And we're proposing a big study through the VA system
to look at this in great detail in progressive MS.
So just to sum up, what I just told you is a theory.
There is a subset of individuals with progressive MS
who have evidence of inflammation.
It's about 30% in our studies, and that's been
reproduced in some larger trials.
They may respond to drugs traditionally used
in relapsing-remitting MS.
That leaves us 70% of patients where we have to do
a better job of getting new drugs
and understanding the disease better.
Multiple sclerosis has traditionally been divided
into three main categories based on the clinical course,
relapsing-remitting, secondary progressive,
and primary progressive.
However, we feel that this is really kind of crude
and that in the future we hope to be able
to classify patients based on the type
and degree of inflammation that they have
and the nature of the damage in the central nervous system.
And if we do this, that's gonna allow us
to diagnose the disease more accurately
and also to develop better, more specific drugs
that will probably be customized in the future
on a case-by-case basis.
So we already have drugs that suppress MS relapses.
I could tell you there's a lot of exciting data
about newer drugs that are even more effective
than the ones we have now.
But we need to increase our understanding
of the basis of progressive MS.
And really the research community,
I'm a big proponent of beginning to focus
on that stage of disease as intently as we have
on the relapsing-remitting stage.
So that's where I'm gonna end this part of the talk.
And now Dr. Braley is gonna tell you about some of those
new emerging treatments for relapsing-remitting disease
and some symptomatic treatments, as well.