>> Thank you very much for
joining us today no matter when

or how you're tuning in.

I'm Dr. John Iskander.

It's my pleasure to welcome you

to CDC Public Health Grand
Rounds for April of 2017

on the National Amyotrophic
Lateral Sclerosis,

or ALS, Registry.

A reminder that Public Health
Grand Rounds has continuing

education credits available for
physicians, nurses, pharmacists,

veterinarians, health
educators and others.

Please see the Public
Health Grand Rounds website

for more details.

Our required disclosure for this
session is noted on this slide.

This month, Public Health
Grand Rounds is streaming

on Facebook Live, and
it's also available

on Webcast Live on our website.

Please send comments
or questions

to grandrounds@cdc.gov.

Along with today's presentation,

we provide interview
segments posted on YouTube

and our website called
Beyond the Data.

This month, I interviewed
both Dr. Paul Mehta

and Miss Becky Kidd, a
person living with ALS.

Please watch those online.

They're quite memorable.

We've also partnered with
CDC Public Health Library

to highlight scientific
articles about ALS.

And we periodically
publish follow-up articles

from past sessions
in CDC's morbidity

and mortality weekly report.

Here's a preview of upcoming
Grand Rounds sessions.

Please join us live or on
the web at your convenience.

In addition to our
outstanding speakers,

I'd also like to acknowledge
the important contributions

of the individual listed here.

Thank you.

And now, to open our
session, we will have remarks

from CDC's acting director,
Rear Admiral Anne Schuchat.

>> Well, thanks so much.

And welcome, people here in
the room, and those watching

from our other campuses
and watching

through the live stream as well.

I personally found the
materials put together

for today's Public Health Grand
Rounds extremely compelling.

And I hope that you will too.

It brought to mind memories
from my first few months

of internship, which is, of
course, a critical period

for every young doctor
in training.

During that period, I cared
for a patient with ALS who was

in our hospital's intensive
care unit for several weeks.

I was struck at the time with
his calm and dignity as he coped

with a body that was no
longer cooperating with him.

And as he tried to help his
family adjust to what he knew

to be the inevitable next phases
of his deteriorating condition.

In 2008, congressional
legislation led ATSDR

to establish a registry to
count, and at the same time,

connect people with ALS with
researchers and partners.

Now, as you will hear, we have
numbers for people affected,

but we have so much more.

The innovative strategies

that the ALS registry
adopted are applicable

to other conditions.

And through the work of this
registry and many partners,

you can see the beginning
of hope for people with ALS

and their families emerge.

So please enjoy today's session.

>> Our first speaker
is Dr. Kevin Horton.

>> So good afternoon.

Thank you all for coming today.

I'd like to extend a big welcome
to our pals or our patients

with ALS who made
the journey here.

We know it's not easy
for you to get here,

but we really appreciate
everything that you're doing.

And especially supporting
the registry.

So today I'm going to
be talking about ALS,

or Lou Gehrig's disease.

And ALS is a rapidly progressive
fatal neurological disease

caused by the degeneration
of motor neurons.

Unfortunately, ALS has a
very high case fatality rate,

as approximately 80% of cases
die within two to five years.

We do know a little bit
about the epidemiology of ALS

in that an estimated 10% of the
cases are familiar or genetic.

And the remaining 90% are
considered sporadic cases.

And of these sporadic cases,
the etiology is largely unknown.

And unfortunately, there's been
no definitive cause to date

that has pinpointed
what's behind ALS.

Now, there have been
a number of hypotheses

that have been looked at.

And these include things
such as chemical exposures,

things such as heavy metals,

volatile organic
compounds, pesticides.

Other things that
have been looked

at include infectious agents,

nutritional intake,
physical activity.

And then probably one of
the ones you've been hearing

in the news lately
is head trauma.

Unfortunately, ALS
does not have a cure.

So currently, there's only
one FDA-approved drug for ALS,

and this is called Rilutek.

But this drug only
prolongs life by about two

to three months, on average.

So ALS, like many
non-communicable disease,

is not a notifiable
disease in the U.S.

And this is an important
thing to note.

This means that doctors

and healthcare facilities
are not required

to report newly diagnosed cased
to state health department,

which, in turn, notifies CDC.

And without these case
counts, there's really a lack

of reliable incidence
and prevalence estimates

for the U.S. So in October,
2008, as was mentioned,

Congress passed and
President Bush signed the ALS

Registry Act.

And I just want to say that
this act was largely passed

because of the grassroots
efforts of patients, caregivers,

various ALS organizations
around the country.

And while the act did not
make ALS a notifiable disease,

it did give us footing
here at CDC/ATSDR

to create a population-based
ALS registry for the U.S. And so

if you look at the
objective that Congress laid

out before us, these
are the main ones here.

Really, to describe the
incidence and prevalence of ALS.

So in other words, how
common is this disease?

Also, to look at
the demographics

of those living with
the disease.

So who gets the disease?

How does it affect Caucasians

versus African-Americans
and so forth?

And then I guess
perhaps the biggest

in my book is what are the
risk factors for the disease?

So given that ALS is a
non-notifiable disease,

ATSDR had to develop
novel case finding methods

to identify and track ALS cases.

And this was particularly
challenging given

that ALS is considered
a rare disease.

And the U.S. has over
300 million people.

So the proverbial needle

in the haystack saying is
certainly appropriate to ALS.

And so after several years

of pilot testing various
case finding methodologies,

ATSDR launched the National ALS
Registry in October of 2010.

And so through our
pilot efforts,

we identified two primary
ways for capturing ALS cases.

The first approach

on the left-hand side applies
a pilot-tested algorithm

to large national databases
to identify cases of ALS.

And these databases
include Medicare, Medicaid,

a couple of databases
from the VA.

And some of the variables
that go

into the algorithm include
the diagnostic or billing code

for ALS used by physicians
and providers.

And this is also
known as the ICD code.

We also look at frequency
of visits to neurologists.

And then we look at
prescription drug usage.

So is a person on Rilutek?

The algorithm helps
classify individuals

as cases or non-cases.

And so those who are
identified as cases go directly

into the registry, while those
non-cases obviously don't go

into the registry.

And those, if you see here,
the potential ALS patients,

that just means we don't
have enough information

to make a decision
one way or the other.

Are they a case or
are they not a case?

And then on the right-hand
side, this is probably

where most people know us from.

This is a secure web
portal that allows people

with ALS to self-identify.

And patients with
ALS answer a series

of online validation questions.

And these are things such as,

has a doctor ever
diagnosed you with ALS?

And depending upon
how they answer,

they're either considered
a case or not.

And those were cases where
the electronically-consented,

and they were set
up an online account

so that CDC can capture
relevant demographic data.

Another important thing about
the web-based approach is

that it allows ALS enrollees

to take brief online
risk factor surveys

that helps CDC learn more about
the possible causes of ALS.

And again, we look at things
such as occupational history,

residential history,
history of head trauma.

And Paul is going to be talking
more about these risk factors.

So cases then from both
approaches are merged,

deduplicated, and
this is to ensure

that we're only counting
a case one time.

So ATSDR, we publish annual
reports of our findings,

and CDC's morbidity
and mortality report.

And our first two published
reports covered calendar years

2011 through 2013.

Our third report for calendar
year 2014 is anticipated

to be published in late
summer of this year

or possibly early fall.

And you're going to hear more

about previous findings
shortly from Dr. Mehta.

So one of the things
that I think is important

to emphasize here is while, you
know, determining epidemiology

of ALS is one of the main
objectives of the registry,

the registry also conducts
other important activities

to help both patients

and researchers learn
more about the disease.

So, for example, the newly
integrated national ALS

Biorepository that we
just launched in January,

we collect pre and
postmortem biospecimens.

And these are things such as
hair, nails, blood, tissue,

from registry enrollees, to help
researchers better understand

the genetics of ALS.

And this is really the only
Biorepository of its kind

that pairs detailed
epidemiological data

with high quality biospecimens.

And to date, thousands of
biospecimens have been collected

from patients around
the country.

And they are currently
being used by researchers

around the country as well.

The registry also
funds external research

to help the ALS community
learn more

about the etiology
and risk factors.

And so to date, we've
funded 13 research projects.

And these include things such
as large scale genome wide

association studies,
or GY studies.

Gene environment
interaction studies,

and studies involving biomarkers
and risk factors of ALS.

Another important activity
is using the registry

to recruit patients
into clinical trials

and epidemiologic studies.

As you can imagine, clinical
trials are very important

for patients, not only to
learn more about the disease,

but to potentially
get some therapy

that may be able to
treat the disease.

And so clinical trial
enrollment, in general,

is pretty difficult,
and it's costly.

The registry actually
speeds up recruitment time.

It increases study sample size.

It helps achieve racial and
ethnic and geographic diversity.

And best of all, it's a
free service to researchers.

And so to date, the registry has
helped scientists in the public

and private sectors to
recruit hundreds of patients

into 26 research
studies at the moment.

And I just want to
say a little bit

about how we promote
the registry.

You know, if you build a
system, you have to make sure

that people understand
that the system exists

and that it's there.

And so we work with a
number of partnered groups

around the country to
promote the registry.

Obviously, patients are
a target population.

And we engage directly with
them through patient forums,

advocacy meetings, ALS walks,
social media and so forth.

We also work with large national
ALS patient organizations

to promote the registry.

And these organizations
represent a majority

of ALS patients throughout
the U.S.,

and they help us
promote the registry

through their multidisciplinary
clinics, through their chapters

and offices, which covers most

of the U.S. Another important
partner are healthcare

providers, such as neurologists.

And these folks are critical
because they see patients

on a daily basis, and they can
really serve as a mouthpiece

for the national ALS registry.

And we interact with
many of these clinicians

at national meetings
and conferences.

ATSDR, we also work with
other federal agencies.

This includes agencies such
as the Centers for Medicare

and Medicaid services, the
Department of Veterans Affairs.

And we work with these groups
to secure administrative data.

We also work with NIH.

And they've been helping this
genotype or biospecimens.

And then we also partner
with research institutions

by providing epidemiologic
data and biospecimens

to help support their
research projects.

And so just in conclusion, from
my slide, this is the first

and only population-based
ALS registry

for the U.S. that's quantifying
the epidemiology of the disease.

As I've mentioned, it's being
used as a recruitment tool

for research, specifically
for clinical trials.

We are awarding funds for
external research to look

at risk factors and etiology.

And we're also providing
epi and biospecimen data

to scientists conducting
research.

And really at the end
of the day, we're trying

to build the evidence to better
describe the ALS experience

in the U.S. And so now I'm
going to turn the presentation

over to Dr. Mehta,
who will be discussing

in more detail the
ALS epidemiology.

[ Applause ]

>> Thank you.

Thanks, Kevin.

Good afternoon.

My name is Paul Mehta,
and I'll be talking

about the known and
unknowns of ALS.

Lou Gehrig was diagnosed
with ALS in 1939.

Over 75 years have gone
by, and ALS continues

to frustrate researchers
and patients with the lack

of information about etiology,
as well as viable treatments.

Currently, there are more
unknowns than knowns about ALS.

No one knows what causes ALS,
but progress is being made.

The latest probable
assessments of ALS

for 2013 show almost
16,000 cases in the U.S.,

or a prevalence rate
of 5 cases per 100,000.

As with any surround
system, it is impossible

to capture all of
the cases of ALS.

We know there are missing cases.

For example, those
patients who get their care

from private insurance rather
than Medicare, Medicaid,

or the Veteran
Administration.

ALS continues

to disproportionately
affect whites, males,

and those between the
ages of 60 and 69.

We are not sure why ALS affects
whites, especially males,

more so than any other group.

This continues to be a
vexing issue for researchers.

There is another group that
impacts ALS as a higher rate.

It is our military
veterans, specifically men.

Those who have served are
at a greater risk of ALS

than those who have not served.

For example, vets
who have served

in the first Gulf War were
twice as likely to develop ALS

as those not deployed
to the Gulf.

We are not sure why
veterans are at risk,

but it may be environmentally
linked.

More research is needed
to investigate etiology.

Sports and ALS have also
been in the news recently,

specifically football.

It is unknown why football
players are at a greater risk

of ALS than the general
population.

But it is believed it may be
due to repeated concussions.

More research is necessary

to fully understand the
pathophysiology of ALS,

especially among
football players.

Nationally, the incidents of
ALS does not occur to be rising.

Prevalence continues
to inch upward

for several proposed reasons.

First, patients are living
longer with confidence of care

from their multidisciplinary
centers

where they get their
care at one location.

These large ALS clinics
provide patients

with their neurological,
nursing, dietary,

physical therapy at one center.

However, not all patients
get their care this way,

and those living in rural areas
see their local primary care

physician or neurologist.

In addition, the register
continues to mature

and does a comprehensive
job capturing more cases.

That is better case
ascertainment.

ALS etiology is elusive, but
we know there are two types

of ALS, sporadic or familial.

Sporadic ALS accounts
for the majority

of cases, approximately 90%.

Familial ALS is the rest at 10%.

Familial can be linked to
certain genes shown above.

There are currently
around 20 genes for ALS,

and more continue
to be identified.

C9ORF72 and SOD1 are the most
commonly identified in patients.

Familial ALS is most
often autosomal dominant.

Parents with this
mutation have a 50% chance

of passing it on
to their children.

Not all who inherit the
gene will get ALS, mind you.

Patients who are diagnosed

with familial ALS typically
show some [inaudible] earlier.

Counseling is available
to these patients as well.

One of the registries
helping explore ALS etiologies

through the completion of
our risk factor surveys.

Currently, patients
who have enrolled

in the online portal have
completed over 60,000 surveys.

These surveys will help
researchers further explore ALS

causes and risk factors.

Currently, the registry
has 17 risk factor surveys,

which are taken by patients

who are enrolled via
the online portal.

The purpose of these surveys is
to shed light on ALS etiology

and whether certain factors
can either be protected

or contributory to disease,
insult or progression.

The surveys are diverse, ranging
from demographics, smoking,

alcohol consumption,
disease progression,

as well as environmental
exposures,

such as the pesticides use.

There is also a survey
that allows patients

to tell us what they feel
may have caused their ALS.

Findings in the first six
surveys have already been

published, and the registry
scientists are currently

examining additional
survey findings.

In addition, these survey
data are also available

for external researchers
for analysis.

In order to further
promote ALS research,

the registry has added the
National ALS Biorepository.

The Biorepository is
part of the registry,

and patients must
enroll in the registry

in order to participate.

The registry conducted
a multiyear pilot study

to determine the feasibility
of the biorepository.

A group of external subject
matter experts provide direction

and deem the biorepository
to be feasible.

It was launched this
past January.

The goal of biorepository is
to promote research in areas

such as biomarkers, genetics
and environmental exposures,

such as to heavy metals
or organophosphates.

The sample collection scheme is
geographically representative.

That is, not all samples
will come from one part

of the country, but will
be distributed based

on demographics, sex, age
and population density.

There are two components
to the biorepository.

An in-home collection, as well
as a postmortem collection.

The in-home collection
will consist of blood,

urine and saliva, with an
annual goal of 675 samples.

The postmortem target will
be 10 collections a year.

There are a number of unique
aspects about the biorepository.

First, the samples
collected are pristine.

That is, not previously used
or leftover from another study.

Second, these samples
will be matched

with a registry survey data,

as well as a global
unique identifier, or GUD,

which will allow researchers to
track the progress of patients

in multiple studies
honestly and securely.

When researchers
request samples,

they will receive
not only samples,

but the actual epidemiological
data as well,

such as demographics,
occupation,

military history and so forth.

Lastly, we feel that nationally

by repository will facilitate
analysts' research on etiologies

and possible treatments
in the future.

Thank you.

>> And it's my pleasure for
Dr. Kasarskis to go ahead

and present on the
provider aspect of ALS.

[ Applause ]

>> Thanks very much.

It's a privilege being here

to address this group
on this topic of ALS.

I'm going to be talking

about basically research
drug development patient care

and how it impacts on
case ascertainment.

And I think part
of my goal today is

to put the considerable
achievements that you've heard

about the registry into
some perspective for those

who may not be directly
familiar with ALS.

So ALS shares some
clinical characteristics

with other neural
degenerative diseases.

So our big three
are Alzheimer's,

everyone's familiar
with, causing cognitive

and behavioral dysfunction.

Parkinson's very much more
prevalent illness causing slowed

movements and tremor.

And ALS, consisting of weakness

of most voluntary
skeletal muscles.

So the question always comes
up, does it affect the heart?

The answer is no.

Does it affect intestinal
smooth muscle?

The answer is no.

And also pervading my comments
today will be the concept

that ALS is a clinical
diagnosis.

So for non-genetic cases,

we really do not have a
definitive imaging biomarker nor

a definitive test in blood
or cerebral spinal fluid.

So it really results or rests on
the interaction between patients

and physicians to come up
with the correct diagnosis.

So the clinical characteristics

of ALS are pretty
much listed here.

So typically, weakness will
begin in one bodily region.

Roughly 80% of the
time in a limb.

So it will begin very
insidiously, very subtly,

with perhaps a flip drop,
or just a little bit

of weakness with hand function.

The remaining 20, 25%

of the individuals will
have difficulty beginning

in the so-called bulbar
region, which means difficulty

with articulation of speech, or
chewing or swallowing function.

So the formation of concepts
in language is preserved,

that the pronunciation and
articulation is imperative.

As clinicians, we look for
many things that are preserved

or normal, or relatively normal.

So sensation is normal,
unless, of course,

you have another cause
for numbness on your feet

like diabetes as an example.

But ALS by itself spares
sensation as a general rule.

Sphincter control, voluntary
control of one's bladder

and bowel function is normal.

Eye movements.

By and large, even though this
is under our voluntary control,

eye movements remain normal,
which was a tremendous statement

because it is daily used by
ALS patients to communicate

if one loses their voice.

And awareness and cognition

and memory are already
spoken of are normal.

So the clinical outcomes of
ALS, you've heard this already

from Dr. Horton and Dr. Mehta.

It's really uniformly formed.

And the way it is a disease that
limits the length of lifespan is

because of ventilatory or
respiratory insufficiency.

So even though we can
stop our breathing

or start breathing
rapidly, so these are

under our voluntary control,
these muscles are also affected.

And so I'll have a slide
illustrating the progression

of weakness keyed off
of respiratory function.

Riluzole was already
mentioned as extending survival

for a short period of time.

And as you've heard already,

most ALS patients have
no family history,

no primary first degree
relative with ALS.

So they're listed as sporadic.

And the 10% are extraordinarily
informative for us

because you can do genetic
testing, map the gene

and create experimental
animals in order to study ALS.

Not shockingly, people
with a family history

with genetic-based ALS, familial
ALS usually have a younger onset

of age, and perhaps a
more rapid progression,

depending on the genotype.

Now, these are illustrations
of what ALS looks like.

And we have many
attendees to this conference

that are not here
physically present.

And so this is going to give a
snapshot of what weakness means

from the neurology standpoint.

Unfortunately, that sort of
lay term is thrown out kind

of trivially, you know,

everybody's having a bad
day, so you feel weak.

But this is what
really weakness is.

This is a patient I videoed

about three months prior
to this man's death.

And so he represents a
very advanced individual.

So in the lower right panel
here, I'm asking this individual

to simply raise his
hand against gravity.

And you can see that
he's unable to do this.

So when we're talking
about weakness,

this is really weakness.

In the lower left panel, we talk

about clinical findings
that we look for.

We look for muscle atrophy.

You can see the muscle
atrophy on this gentleman.

And we look for fasciculations

or spontaneous contractions
of muscle.

And this will be illustrated
here in this slide as well.

So it comes as no surprise

that this gentleman is
extraordinarily weak.

And these muscle fasciculations
usually are not troubling

to the patient, but
they're present.

You know, most of the time

by themselves they don't
merit medical treatment.

But it's one of the
clinical findings we look at.

Now, I already mentioned
about bulbar weakness.

And this gentleman is going
to be protruding his tongue.

You could look at this and see
also atrophy on his tongue.

And you won't be able to see
fasciculations on his tongue

because I'm asking him
to protrude his tongue.

But this is all that he can do.

So it's not a shock
that he's not going

to be pronouncing
his words clearly.

It's not a shock that he's going
to have difficulties chewing

and swallowing, swallowing
even simple stuff

like water or pills.

And the video on
the left is going

to be him responding
to a question.

So you'll hear the dysarthric
speech, meaning the difficulty

with pronunciation, and this
should come through pretty well.

[ Inaudible ]

So without even really
examining,

and besides these video clips,
you see the preserved features.

You saw him move his eyes
from one position to another.

So his eye movements
are preserved.

He's a very alert,
very intelligent man.

And he speaks complete
and clear sentences.

Mispronounced, but
complete and clear.

So he doesn't have any aphasia

or some central processing
with speech.

This is a slide that
illustrates the cause of death.

And this came from a CNTF
study that's been published.

This is a representation of
percent forced vital capacity,

which is a test, a
muscular test of breathing.

And this is used very commonly
in clinical drug trials.

And on the far right at zero
is the cohort's death due

to respiratory insufficiency.

And these data are backed up in
reference to the time of death.

And you can see at the time
of entry into this study,

the group as a group by

and large had a forced
vital capacity of around 65%

of normal, meaning already
they've lost considerable

breathing strength at the
time they were entered

into this study.

And you can see month
by month by month

by month the ventilatory
power is diminished.

And within about three months of
their ultimate demise, you know,

the breathing capacity
is only 1/3 preserved.

This is an old study.

It's, in a way, a
natural history study.

Currently, we intervene actively

when the forced vital
capacity gets to about 50%.

So there are a lot of clinical
triggers that encourage patients

and clinicians to
intervene with, for instance,

non-invasive ventilation
at night.

But this illustrates the point

of why ALS shortens
one's lifespan.

This slide illustrates some
of the topics that were talked

about already in terms of
the motor neuron disease.

In Europe, this would be known
as a motor neuron disease.

In the United States,
we say ALS.

So on the left panel in red,

this is not an Atlanta
express rate.

These are axons or projections
from motor neurons in the cortex

that project all the way
down to the spinal cord.

So when you think about this,
in order to do a wheeled motion,

like me waving my hand,
the first motor neuron,

the final common
pathway out of the brain,

is motor neurons in the cortex.

And a single nerve cell will
project physically and connect

with a motor neuron
in the spinal cord.

So depending on how
tall you are,

it might be a meter in length.

The second neuron in the
spinal cord is illustrated

on the right side.

These are the spinal
motor neurons.

These also are very
long neurons.

They will project and
connect with skeletal muscle.

And so for me to raise my
hand, nerve cell number one is

in the brain, nerve cell number
two is in the spinal cord,

connecting to the muscle,
allowing me to make that motion.

These are the cells
that are vulnerable

to ALS type degeneration.

These are the cells that
degenerate and eventually die.

And needless to say when the
electrical message does not get

through to the muscle,
it does not work,

and you get muscle
atrophy and weakness,

such as was illustrated.

Now, even though these
nerve cells are large,

you cannot image these
directly currently

with imaging techniques
such as MRI or PET scan.

I think that will
change in the future.

But currently, that's the case.

So the diagnostic
procedure is a challenge.

And it's a clinical diagnosis.

And so we look for
these clinical signs

that are illustrated
in the previous slides

and we verify many
things being normal.

But at the end of the day,
it's a diagnosis of exclusion.

So we exclude mimics that can
cause progressive weakness.

The list is quite long.

Some of the testing
will involve MRI imaging

of brain and spinal cord.

Because, of course, if you have
a stroke or a tumor or something

like that, that could
cause weakness.

EMG and their production
study, I don't have time

to go into the details.

Every patient in
the room is cringing

when they think about this.

It's not exactly the
most pleasant test.

But this directly examines
whether the problem is

in the muscle causing
weakness or backed

up into the spinal cord.

And we do lots and lots of
different laboratory studies

to exclude other illnesses

that conceivably might
cause progressive weakness.

I put down here at the end all
patients must have a second

opinion from another
neurologist.

I think this is a
dogmatic statement.

But when you're dealing with
an illness with consequences

as I've described, this is
important in my judgment.

So at the end of the day,
how good are neurologists?

Do we have any bragging rights?

Well, actually, we do
a fairly decent job.

So the clinical diagnosis has
about a 95% sensitivity compared

to autopsy examination
of brain and spinal cord.

So, you know, very, you know,
agreed upon diagnostic criteria,

they go by the names of
the [inaudible] criteria,

the early house, so we
follow these criteria.

And if we apply them and
have two neurologists,

basically we're doing a
fairly reasonable job.

A recent study coming out of
Scotland illustrates this point

about 44 individuals in their
district came to autopsy,

and the diagnosis was confirmed.

So despite these challenges,
epidemiologic research,

as we have heard, is possible.

We have tools that quantitate
muscle power, which are used

for drug testing
outcome measures.

We have a self-rating scale,
the ALS functional rating scale,

which is adopted to computer
use over the phone, caregivers.

And this will help map
the progression of ALS.

Illustrated here is a woman
doing pulmonary function

studies, such as you saw the
FVC measured, and survival

of ventilatory ventilation
free survival is another

outcome measure.

There are other measures
of muscle strength

and power and dexterity.

Physical therapists first
do the Timed Up and Go test.

This is the Purdue
Pegboard because it looks

like a cribbage board.

These sorts of things are done
as clinical outcome measures

in various combinations
of different drug studies.

So by the time people
become clinically impaired,

actually the majority of
vulnerable motor neurons,

it is believed, have
already degenerated and died.

So clinical drug studies
require a large number

of patients possibly, and this
is a major barrier to progress

in terms of time and distance
and out-of-pocket expenses.

So with all of that,
I'm standing here

with reasons for optimism.

I think the ALS research
committee,

or community, is expanding.

We're extraordinarily
passionate in what we do.

I think the national
registry stands

as our number one
example of that.

So my bold prediction, causes
will be found, genetic,

non-genetic causes
will be found,

and further treatments
will be developed.

So I'm going to turn
over to Ed Tessaro

who has fortunately
joined us to talk

about patient life with ALS.

>> Hi, everybody.

[ Applause ]

Hi, everybody.

So I'm Ed Tessaro.

And I was diagnosed at Emory
Clinic in 2009 with ALS.

I'll tell you today in the
few minutes we have briefly

about my patient experience, the
clinical trial participation,

the wonderful times I've had

with ALS families
and persons with ALS.

We call them pals.

And last, a little
bit about purpose

that I've come to understand.

So to begin with,
I love my life.

I live it with no regrets.

I've never considered myself
a victim of the disease.

Because I believe
in my heart that all

of us have a wheelchair.

In my case, it's quite literal.

400 pounds of plastic
rubber and hydraulics.

And I can kill people if I'm
not careful with that thing.

But with everything that
goes on in my long life,

every family I know has had
crisis, whether it's caring

for children or the dashed
hopes of dreams or careers

or family emergencies,
life and death issues.

We have to reckon with
the human condition.

And we can bend the
curve a little bit.

But we can't change it.

We can be kinder to people.

We can listen better.

We can seek out those from
whom we have much to learn.

And generally living our life
that way is quite a salve

quite a bromide.

The last one, in my case,
is important, having to do

with seeking out people that my
wife and I have enjoyed so much.

Those families have
changed our lives.

I think there's 150 of them,
just to pick a round number.

And it's been a very
big deal to us.

It also means learning about
activists and thought leaders

in the national community
of ALS.

And you see a few six people
in front of you there.

Seeking out those individuals
and their very private lives

that they've decided to make
public has been also very good

for the science,
for the fundraising.

Let's be clear about it.

It's very important
in this business.

And we would all agree that ALS
could be the most frightening

disease in history.

There's a good argument
to be made.

So the ongoing struggle to
encourage newly diagnosed people

to come in and talk about
their condition is a big deal.

By the way, what I
didn't mention is Ed Rapp

on the left will be here in
October to honorary chair

of our annual MDA Night of Hope.

So another national leader
who brings his spirit to a lot

to help us do what we do.

But there's an ongoing struggle

to encourage newly diagnosed
patients to come forward.

We've talked about the
fact that it's complicated.

But people have this tendency
to hide, to go inside,

to not want to have
conversations with friends

and family about the disease.

And we just have to know

that those first tendencies
have to be dealt with.

So the cost of living with ALS.

We'd all agree, and the
expenses listed there

on the screen are pre-diagnosis,
the medical community expenses.

But my point today is about the
post-diagnosis personal cost

that those in my community
have to go through.

First of all, every
disease or injury is costly.

But no injury or
disease, I think,

requires as much personal
expense as does ALS.

The basic requirements
to live with it involves,

as many of you know, home
renovation, vans with ramps,

expensive power chairs,
lifts in your home,

every sort of ramp
on the outside.

It's in the 100 to
150,000 range,

just about when you get started.

So the personal cost has to
be understood because the fear

of family financial
ruin is a very big deal.

And the consequences of
that fear are more physical.

So it's quite a vicious
circle in that regard.

So there's much to understand
about how we have to pay

and how we need help and
where do we go for resources

that we'll talk a little
bit about in a minute.

So the next subject
is the openness

of the medical community
towards researchers

and investigators include toward
new patients and their families.

Outside of major city centers
like Atlanta, patients are often

in alert, because as my
counterparts here have said,

not everybody is schooled
in an organ disease

or rare disease with
30,000 people.

Even in Atlanta with
my insurance plan,

which I would say is very
good, I was misdiagnosed

with spinal stenosis
eight years ago.

I had a major back surgery, only
to find that orthopedic people

and neurological people
don't use the same language

when they talk.

So if it can happen in
Atlanta with the kind of care

that I've had, I know
it can get even worse.

Why is that language
not more common?

I'd say that's a great question
to ask as we move forward.

It should be.

So next, the patient process
to be available to participate

in a clinical trial, that's a
pretty controversial subject,

and to get information
about those trials.

Why are only 10% of us

in a clinical trial
or study in America?

It's not like we
have better options.

You'd think the doors would be
beaten down by people trying

to get into this
type of research.

But there are obstacles,
and it won't be a surprise

to anybody in the room.

Delayed response to questions
on the trials we see listed

on clinicaltrial.gov, which is
a great site, but it's not easy

to get follow-up questions.

It's not easy to understand
the status of those trials.

Because if they go well, there
are silos to be protected.

If they go poorly, nobody
really wants to talk about them.

But patient issues
are just difficult

to get the answers you want.

Lack of awareness and trial
options, the burdens associated

that Ed mentioned with
travel and cost are factors

that also keep us
outside of the research.

Common doctor factors,
surprisingly, are the failure

to personally advocate even
to their own ALS patients

for involvement in
a study or trial.

In a study that I read,
it's called the absence

of physician influence.

Now, you would think that
would be the opposite.

But again, it's a
difficult road sometimes.

So the next point is
the counsel we need

as newly diagnosed patients,
to accept the reality

of our disease and how to
turn it into a life force.

Sounds kind of theoretical.

But there's really
little personal counseling

in the clinic playbook
that exists today.

It doesn't mean there aren't
people there to listen.

There are.

And the ALSA and MDA
clinics are outstanding.

But there's more that
the community needs.

And I'll use an example
of the Pacific Institute

on the west coast that for
decades had been helping people

through obstacles that they want
to change, but they can't do it.

So organizations like
that teach us to want

to change our experience,

not wait for our
experience to evolve.

And my wife and I have
learned in eight years

of informal conversations
in this way

that attitudes are
developed, they're not born.

And there's five things
that-- they're cliches,

but they continually come
back and mean something.

And that's to be
purposeful, to be selfless,

to be self-determined,
empowered and courageous.

Sure, cliches, but
that's what you lose

when you get a diagnosis
like this, and we've got

to fight to get it back.

The next point has to do

with the resources we
have at our disposal.

There are many more
than you think.

And those two organizations,
the MDA and the ALSA

and their Georgia chapters
are just outstanding.

They've been so good for
my family and the friends

that I've come to know.

So I don't think anybody needs
a prompt from me to go and look

at what options there
are in those sites.

But there are many.

They do so much service,
so much research both

that it's a fine thing.

ALSUntangled is a great way

to distinguish real
medicine from fake science.

And there's people
who contribute to that

from all over the world.

But it tries to tell
you that this supplement

or that drug being
tested in Morocco

or something is not
as advertised.

And they don't have any crystal
ball, but it's a great source

to help cut through
some of that blather.

The next example is-- and
this is controversial--

and that's the inherent
unfairness

of a double-blinded
clinical trial.

You won't find an ALS patient
who just recoils at the idea

of going through what it
takes to be in a trial

and perhaps be that placebo guy.

And until I went along with
many, some in this room,

ALS patients, when we went to
the conference last year in DC,

about clinical trial ALS
preparation, did I really learn

that from a science standpoint,
that will never align

with a patient with a
fatal disease.

I was an example, my Ceftriaxone
trial five years ago,

six years ago, I had a Hickman
catheter in my chest for a year,

and I carried around frozen
study drug everywhere I went.

Movies, restaurants.

I had to have that study drug.

And I ended up being
the clinical trial.

But I ended up being
the placebo guy.

But until I understood
at that conference,

and when the trial foiled,

I understood why it
has to be that way.

Because if it's not
double-blinded,

what did we learn?

So one of the roles I try to
take in my layman's ability is

to try to tamp down some of that
anger that comes from people

who are told you don't
qualify or you can't get in,

or if you do, you may have
to be a part of a 50% blind.

So, you know, people
do get angry at God,

at science, at policymakers.

And they always will because we
have so much skin in the game.

But that's important.

Then next, the ALSA, ALS
plateaus and reversals.

This is a wonderful site
that Dr. Rick Bedlack at Duke

and others continually study and
investigate within their means,

things that are outside the box.

Because we all know there are
no solutions that are going

to cure anybody inside the box.

So that team of people
publishes information

about what they think
is going on out there.

They do their own trials on
food supplements and things

that maybe wouldn't attract Big
Pharma and that sort of thing.

So that's a very big deal.

So I started a clinical trial,

I started a study drug
just a few months ago

that I wouldn't have known of
at all without going to do that.

So I'm going to end on a subject
also very close to ALS hearts.

And it has to do
with legislation

and FDA-approved
programs, Right-to-Try,

extended access programs,

both of which getting
a good run these days.

Right-to-Try, as you know, many
of you know, has become law

in 33 state legislatures.

And it was Scott Gottlieb
taking over at the FDA.

It may well have some legs.

It will get a good
look, we know.

And while I'm talking
about RTT labs,

I'll have to honor a dear friend

who passed away last
year of cancer.

He was an ALS trial
patient with me at Emory.

That's Ted Harada of Atlanta.

He has many friends
in the community

and way many friends nationally,

because he's been a tireless
advocate, haunting the halls

of state capitals and national
capitals to make the case

for better understanding and
better access for patients

through his own personal
point of view

and his force of character.

So Ted, we miss you,
but thank you.

Thank you.

Yes.

[ Applause ]

Expanded access programs are
a little less controversial.

They've been around for decades.

In the 60s, experimental
cancer drugs

and HIV AIDS drugs
reached thousands of people

under the expanded
access program

and compassionate use premise.

So that's a fine thing.

ALS patients don't
have access today.

And there's a real stumbling
point between doctors, patients,

Big Pharma, study trial people,

because they don't want
their results compromised

or they don't want, you
know, lone wolf people

out there claiming
one thing or another.

So the way I think
of EAP is that it's

about the patient is
dying, the patient can't get

in a clinical trial,
and the primary goal

of these programs is for the
patient treatment, not research.

So I think if we keep the
context of the discussion

within those objectives, I
think we'd have more converts.

And there should be a
way forward for that

in all of our communities.

So thank you for
the long listen.

It's a tough subject.

But maybe we can fling
open a door or two

in the next couple
of years of research.

I know a lot of smart
people are working on it.

And we'll change this
disease from a fatal disease

to maybe a chronic condition.

That's not sexy, but I
don't use the word cure.

I'm happy just to spell
this thing and get all of us

to another chapter in our life.

Thank you very much.

[ Applause ]

>> We can take some
questions from the audience.

[ Inaudible ]

>> Testing.

Can everybody hear?

S I'd just like to thank the
panelists for an excellent,

outstanding presentation.

I actually have two questions,
if you would allow me.

So the first question
is for ALS patients.

What's the most common
type of palliative care,

and does that include any
kind of physical therapy?

That really makes a difference.

And that's for Dr. Kasarskis
or Dr. Tessaro, or Mr. Tessaro.

>> I prefer Ed.

>> Ed. And then the second
question is for Dr. Horton.

You may have said this,
and I may have missed it.

But for the registrants
in the registry,

is there a postmortem facet
associated with that in terms

of data collection that the
registrants have to agree to?

Do you understand that question?

>> So I'll answer the
question about physical therapy

and massage therapy and
occupational therapy.

These are the real
nuts and bolts

of what our multidisciplinary
clinics do.

You may have personal
experience with that,

but in one clinic visit, which
for the patient lasts two

to three hours, they see PT
and OT, those instructions are,

you know, educated
and transferred

to the patient and family.

I mean, first off, you know,
ALS you cannot do by yourself.

I mean, it's a family
disease, a family condition.

So many people are involved
that have to take over more

and more of the function.

I mean, you saw the gentleman

that I illustrated
how weak he is.

I mean, he's not going
to comb his hair,

not going to brush his teeth,
not going to wipe his bottom,

not going to rub his nose.

So all of those functions
have to be taken

over by family members.

And there are a lot of
physical therapy things

that they have to learn.

I always tell patients that if
my wife had ALS, I would have

to learn how to do this too.

You know, you can
read it in a book,

but until you have
hands-on experience of how

to perform these functions,
you really don't know.

I presume I'm preaching
to the converted here,

but I think it bears repeating.

So a lot of those insights
from our colleagues

in the different disciplines
are transferred to patients,

and these things,
the clinics, I think,

anticipate problems
before they actually come.

And I think that that
is much appreciated

by our patients and families.

>> I'm not exactly clear
on what you're asking,

but one of the things
that we wanted to do is

to make this registry
as useful as possible,

not only for patients, but
for researchers, as well.

So one of the things that
we do, constantly do,

is we go out to conferences
and we meet with patients,

meet with researchers,
is to ask them,

how can we improve
this registry?

And one of the things that
was brought up is, you know,

the collection of samples from
living people and the collection

of samples from people who pass
away and they're generous enough

to donate their body to CDC
to harvest the biospecimens.

And so I think that we have
done a good job, at least we're

on the way to collecting, you
know, samples that can be used

for research purposes.

I mean, we probably won't
use them here at CDC,

but meeting us here,
collect the samples for CDC,

but for external scientists.

And so the more we can
shed light on this disease,

whether it's through EPI data
or biospecimens or a convert

of both, and that's
what we're trying to do.

>> One question from
Paula very quickly.

>> Yes, we have a question
from our Facebook audience.

They want to know, why not push
to make it a notifiable disease?

>> So that's a very
good question.

The issue there, we actually
get that question quite a bit.

One of the things, though, is
like when it comes notifiable,

it's for an STI or an HIV,
which is reported back

to us eventually, there are
states, and since currently

when it comes to resources,

reporting on let's say the
STIs, HIVs from right now.

But the premise is, because
of lack of resources,

if we say let's go out and back
ALS notifiable, then Parkinson's

and Alzheimer's and other
conditions may also, you know,

have their group saying, let's
also make it notifiable as well.

So the resources I don't believe
are there currently to go ahead

and make it notifiable at
the state level to go ahead

and report it to
the national level.

So that currently is just
not feasible at this time.

Yes, ma'am?

>> So first I'd like to thank
Ed for reminding us

that everyone has their own wheelchair.

But I have a question
about the registry.

Congratulations for
establishing it.

It sounds really
exciting, and something

that could serve as a model.

I'm very curious about
you have two methods

for getting patients.

One is through the
databases, and others is

through just people signing up.

And what's the relative
proportion of people

that you get from the
different methods?

And what percent
of all ALS patients

in the country do you
think are in the registry?

How much overlap do you see
between the people that you get

from the databases and
the ones who sign up.

And then lastly, and maybe you
can't deal with all of these,

you said you contact people
who are in the registry.

But some of those people you've
only gotten from databases,

not from them signing up.

And so can you contact
those people?

>> No, we can't contact
individuals

from the national Admin data
like Medicare, Medicaid.

We can contact them
with their consent

from the actual online
portal itself.

Your question was to proportion

of the databases compared
to the online portal.

It's about 85/15.

So a lot of the cases are
coming from Medicare, Medicaid,

and their VA system itself.

And there's an overlap as well.

So while I'll still see
folks, patients also

in the database used as well as
in the online portal as well.

>> I'd just like to follow up.

One of the things that
we are trying to do is

to determine how complete are
the data, as you mentioned.

And the data is only as good
as what you have in there.

So we're doing a couple things.

One is we're using
statistical techniques.

Capture, recapture.

I'm not going to go into that.

But it's a way for us to gauge
how complete the data are.

And then we've also done
active case finding efforts

in three states in eight
metropolitan areas using an

active approach versus more
or less our passive approach.

And so we're actually
comparing the cases found

in the active approach with
those found in the registry

to see, are we finding more
cases out there that, you know,

we should be capturing?

So it's an ongoing challenge,
not only for this registry,

but for any registry or any data
collection that you're doing.

You want to know how
complete the data are.

And so these are some of
the things that we're doing

to try to figure that out.

>> And just to quickly mention,
with any surveillance system,

like which this one
is, it's impossible

to capture all the cases.

>> Doctor Redd you
have a question as well?

>> It's a really
very nice session.

And it really reminds
me of Grand Rounds

from the medical training.

A question about that curve
that shows the progression,

it made me wonder whether--

I was thinking about
an incident event,

when a person actually goes
from not having the disease

to having it, and how far back
people think that is in terms

of the loss of neurons.

>> Yes, that's an
excellent question.

>> Did you all hear
the question?

>> Yeah, I think he
was on the microphone.

So there is one way of trying to
gauge the speed of progression.

I didn't make the comment, but
every patient is individual,

so we have some individuals, of
course, that progress rapidly,

and some that have
progressed slowly.

That's obviously
a group average.

And there's one technique

of saying what your ALS
functional rating scale is the

first time you encounter the
medical system and back it up to

as best you can tell
from historical data

when someone first
develops weakness.

But we know based on
the EMG information

that the process biologically
in the spinal cord goes on,

has gone on for a
long period of time.

Because when you think about
it, I didn't get into this, but,

you know, all the motor neurons
don't die off at the same time.

So we'll have one die off

and the other remaining
ones will sort of sprout

and take over the territory.

So as far as the patient is
concerned, I'm still strong.

And, in fact, you know,
Lou Gehrig was mentioned.

He was diagnosed in '39.

That's not when his
disease began.

It began in 1938.

He played the entire
year, you know?

And his batting average was
quote only 295, you know?

The previous year was like 345.

So he had a drop-off
in function.

But he continued to play.

And he played every single game.

So, you know, it's a
little bit of an artifact

of when you're diagnosed.

And that's part of, I think,
the benefit of the registry,

is the awareness
factor is out there.

So a lot of times patients
will come to the clinic

with their Google
online search of papers.

And they might be the
ones who have suggested

to the primary care doctor,
I think I have ALS, you know?

We have some backfires
on that strategy.

But still, the point is

that I think the awareness
factor is getting patients

in a little bit earlier.

The truth of the matter is that
in Europe and North America,

it's roughly 9 to 12
months before you go

through this diagnostic process
before you have a confirmatory

second opinion about ALS.

Still takes a long
period of time.

And, you know, biologically,
those are motor neurons

in the spinal cord and
brain that are dying.

And so a drug, a purported
drug treatment is fighting

for the remaining 30 or 40%

of the natural endowment
of motor neurons.

So it's a challenge.

I realize you could wipe out
those comments and say put

in Alzheimer's and
put in Parkinson's,

and I think the same
premise is there.

It's an uphill battle with these
neural degenerative conditions.

>> Thank you all very much.

We're going to have to end our
webcast and our session now.

Thanks very much to
all of our presenters.

[ Applause ]

For those who submitted
questions online,

you will receive answers.

And please join us next
month when we are going

to rebroadcast last
month's session

where we had some
technical problems.

Thank you very much.