Vol. 11, No. 3 • WINTER 2013 - Alpha

Vol. 11, No. 3 • WINTER 2013
1
A MAGAZINE OF THE ALPHA-1 FOUNDATION
ALPHA- -TO-ONE
Practical advice, personal experiences, and
pertinent news for people touched by ALPHA-1
Driven
to helpfind
a Cure
PAGE 4
NONPROFIT ORG
U.S. POSTAGE
PAID
MIAMI, FL
PERMIT # 8124
The Prototype
PAGE
PAGE 66
Saving More Lungs
PAGE 10
A Wonderful Year
PAGE
PAGE 12
12
FOCUS
ON THE
FOUNDATION
A year of accomplishment
for Alphas around the world
We marked the 50th anniversary of Alpha-1 in big ways
and small ones. Alphas worldwide are uniting for action.
ifty years ago, when Carl-Bertil Laurell and Sten
Eriksson published their research paper on the
discovery of Alpha-1 Antitrypsin Deficiency in
1963, they planned to study the family connection in Alpha-1 – something they suspected from the beginning. But there was no way they could have known just how
important their landmark paper was.
The alpha-1 protein they found has changed the world.
See What the World Owes to Alpha-1, page 6, for the story of
how Alpha-1 became the model for a host of seemingly unrelated conditions – including Alzheimer’s disease and some
other dementias; cystic fibrosis; mad cow disease; some
forms of Parkinson’s; and Huntington’s disease.
Alphas are changing the world, too. We are deeply involved
in research, fundraising, awareness and advocacy going way
beyond the relatively small world of Alpha-1, still listed as
one of the rare “orphan diseases.” Alphas are leading the
charge for more research on and awareness of COPD, with its
many millions of patients worldwide, and liver disease, too.
See our cover story (page 4) on Richard Johnson’s campaign
to win the Betty Jane France Humanitarian Award, which
can bring $100,000 for research and even more important,
huge awareness for Alpha-1. We urge everyone to vote for
Richard every day till Dec. 5 – our website home page makes
it easy! That’s alpha-1foundation.org.
And see pages 12-13 for a roundup on many of our 50th
anniversary events this year.
At the flagship event, the 4th International Alpha-1 Patient
Congress in Barcelona, Alphas from 23 countries around the
world shared thoughts on the most important needs of the
Alpha-1 communities in their countries. They agreed to form
an international working group to support communication
among Alphas and to work in unity to achieve those vital
goals. And the Alpha-1 Foundation promised to help.
Keeping our promise, on page 13 we announce the hiring of
a Global Program Director, who, with the help of a provisional steering committee, will begin work on an online
global communications platform. She will act as the facilitator of communication among Alpha-1 organizations seeking
to achieve those vital goals.
We wish you and your loved ones a happy holiday season
and a new year of health, happiness, and prosperity.
For information about organizing a fundraising event to benefit
Alpha-1 research, contact Angela McBride at 1.877.228.7321,
Ext. 233, or [email protected]. To learn
more about ways to give or to make an online donation, visit
www.alpha-1foundation. org/help/.
F
2
1
ALPHA- -TO-ONE
Practical advice, personal experiences, and pertinent
news for people touched by Alpha-1
VOL. 11, NO. 3
Published by the
Alpha-1 Foundation
3300 Ponce de Leon Blvd.
Coral Gables, FL 33134
1.877.2.CURE.A1 (228.7321)
www.alpha-1foundation.org
Alpha-1 Foundation Board of Directors
Executive Committee
Gordon E. Cadwgan, Jr., PhD,* Chair
Kenneth A. Irvine +, Vice-Chair
Martin Zamora, MD, Secretary
James Quill*, Treasurer
William J. Martin II, MD, Scientific Advisor
Members
Jeanine M. D'Armiento, MD, PhD
Shane Fitch +
Elizabeth Johnson*
John S. (Jack) Reid +
Joe Reidy*
Stephen I. Rennard, MD
Judith Simon*
Director Emeritus
Marilina V. Fernandez+
Editorial Board
Bettina Irvine* Michael Krowka, MD
William J. Martin II, MD Jane M. Martin, BA, CRT
Miriam O’Day Ab Rees*
Bruce C. Trapnell, MD John W. Walsh*
Executive Editor
Marcia F. Ritchie
Managing Editor
Bob Campbell
Contributing Editors
Maria Virginia Deliz
Angela McBride
Linda Rodriguez
Robert A. Sandhaus, MD, PhD, FCCP
Eileen Spiegler
Contributors
Cathy Carlomagno
Tom Neile
Advertising
If you are interested in advertising, please contact
Bob Campbell at 888.825.7421 ext 230.
ALPHA-1-TO-ONE is published by the Alpha-1 Foundation with the support
of our advertisers. No part of ALPHA-1-TO-ONE may be reproduced in any
form by any means without prior written permission of the Alpha-1
Foundation. The contents of ALPHA-1-TO-ONE are not intended to provide
personal medical advice, which should be obtained directly from a
physician. The Alpha-1 Foundation is not responsible for the accuracy
of information expressed in advertisements in this publication.
Letters to the Editor. ALPHA-1-TO-ONE would like to hear from you.
Please send letters to the editor at the Foundation or e-mail us at
[email protected]. Letters may be edited for clarity and length.
The Alpha-1 Foundation is
dedicated to providing the
leadership and resources
that will result in increased
research, improved health,
worldwide detection,
and a cure for Alpha-1
Antitrypsin Deficiency.
* Diagnosed Alpha-1 Antitrypsin Deficient
+ Diagnosed Family Member
1.877.2.CURE.A1 (228.7321)
Vol. 11, No. 3 • WINTER 2013
1
A MAGAZINE OF THE ALPHA-1 FOUNDATION
Inside ALPHA- -TO-ONE
Features
4
6
6
10
12
16
17
SPOTLIGHT
Richard Johnson, Alpha-1 ambassador
He campaigns to win $100,000 for research and a year of Alpha-1 awareness
FRONTIERS
The molecule that changed almost everything
The world owes more than you think to Alpha-1 and Carl-Bertil Laurell
Saving lungs and lives
Many more donated lungs can be used, thanks to Sharon McRee’s idea
ALPHA LIFE
What an anniversary year it was
Following up on a call to action from Alphas around the world
The first family of augmentation
A.J. Mosley lived a life both humble and heroic
IN YOUR INTEREST
Good news, bad news on Medicaid expansion
The working poor can get insurance -- except in 25 states that opt out
ALPHA 411
Spreading the word
Facebook, Twitter and email, powerful tools to spread Alpha-1 information
The perfect fit
Susan Clarke’s whole life prepared her for helping other Alphas
10
20
16
See us in Times Square
21
If you’re in New York City this holiday season,
you just might see our Alpha-1 Sucks the Life
Right Out of You video on the 26-foot-wide by
20-foot-tall CBS screen as you walk through
Times Square. If you aren’t so lucky, see it here:
https://vimeo.com/79419667
facebook.com/alphafriend
www.alpha-1foundation.org
twitter.com/alphafriend
3
SPOTLIGHT
4
The drive
for a cure
speeds up
“H
ello, Denver, this is your Alpha-1
News,” says 5-year-old Lucas Johnson
as he pretends to give the weather report to a cellphone camera. Behind
his smile and bright blue eyes, you would never
guess that Lucas has Alpha-1 liver disease, as does
his sister, Grace.
“The weather is cloudy, and remember if you smell
smoke, pinch your nose and go inside,” continues
Grace, a little expert on air quality at the age of seven.
This fall the Johnson family has sparked one of the
biggest awareness campaigns the Alpha-1 community has ever seen. Richard Johnson has been nominated for The NASCAR Foundation’s Betty Jane
France Humanitarian Award. If he wins, the
NASCAR Foundation will donate $100,000 to
Alpha-1 research, and Johnson hopes that Alpha-1
awareness will get a huge boost.
Johnson and his wife, Sarah, of St. Johns, FL, discovered Grace and Lucas had Alpha-1 in 2008,
when Lucas was born with severe jaundice. After
Lucas was diagnosed at two months, Grace, then
age two, was also tested. The couple was devastated.
“You start reading about liver transplants and lung
transplants, and you have 2-month-old child,” says
Johnson. “It’s scary.”
Fear soon gave way to determination. “After a lot of
tears and guilt, we decided we were going to become much more involved,” Johnson says.
Long before he knew how close to home it would hit,
Johnson was finding a way to help others. In 2003,
he and friend David Glocker started a golf tournament to raise money for a specialized autism school.
“We were just a couple of guys who decided we
wanted to help someone [in need],” Johnson says.
Their efforts did help: The Jacksonville School For
Autism is celebrating its 10-year anniversary.
“When you do charity work, it is amazing how
things seem to find you,” Johnson says.
In 2008, his desire to do good had new urgency.
“We’re still huge supporters of the school, but at
that point the tournament had become self-sufficient,” Johnson says. “We said, ‘we need to do
something for our kids now.’ ”
He and Sarah traveled the country speaking at
events, telling families about the importance of early
Alpha-1 testing. They took part in support groups
and eventually became support group leaders. They
spearheaded the Foundation’s family testing program, held an annual letter-writing awareness campaign, and attended fundraising events.
“Our biggest concern is getting parents involved
and aware,” says Sarah Johnson, adding that testing
is more frequently done on adults than children. “If
we can treat the liver while they’re young, we won’t
have to worry about the lungs.”
Johnson works hard to dispel the perception that
Alpha-1 is a condition suffered only by adults. He
notes that larger companies have just begun research on developing drugs for Alpha-1 liver disease. “It’s just in the last year or two there has been
more money for liver research,” says Johnson, who
works in the pharmaceutical industry.
Richard Johnson was presented with his official
NASCAR jacket by NASCAR driver Austin Dillon,
the DRIVE4COPD Ambassador.
1.877.2.CURE.A1 (228.7321)
“We know how much money and
time goes into creating a drug,
and that’s what drove us to raise
funds to find a cure,” Sarah Johnson says.
In 2012, Johnson started another
golf tournament, this time for
Alpha-1 fundraising. In its second
year, it raised more than $53,000
and has become so popular there
isn’t enough space for everyone
who wants to play.
The Johnsons have shown “incredible leadership,” says John
Walsh, president and CEO of the
Alpha-1 Foundation. “Richard
studied until he found what could Lucas and Grace Johnson, with their father, Richard at the Daytona
be done to make a difference. He’s Speedway.
provided that inspiration, that
spark, that’s ignited a whole
suffers from a rare condition that left her wrist
community.”
joints deformed.
Johnson’s uncle Buddy, his mother’s oldest brother,
She has urged fans to vote for Johnson on her social
died in his early 50s. Although they don’t know the media sites. She posted on Facebook, “Let’s make
cause of his death, Johnson’s mother and aunts have
this family’s dream a reality,” with a photo of Johntested positive for Alpha-1. Johnson is a carrier. “I
son and his kids.
have a good gene and a bad gene,” he says. “You
Johnson has also gotten a huge boost from
just wish you could’ve passed on the good gene.”
Grace and Lucas are enrolled in the Childhood Liver DRIVE4COPD, which is the country’s largest public health initiative raising awareness of chronic obDisease Research and Education Network (ChiLstructive pulmonary disease (COPD) and
DREN) study, sponsored by the National Institutes
NASCAR’s official health initiative since 2010.
for Health and the Alpha-1 Foundation. It is yieldDRIVE4COPD organized a massive awareness event
ing results: In 2012, the study found that Alpha-1
at Phoenix International Raceway Nov. 9 in which
children with liver disease often have portal hyperAlpha-1 youngsters were paired with racecar drivers,
tension, but that most are still doing well. It is the
including DRIVE4COPD ambassador Austin Dillargest longitudinal study for children with liver
lon, to create artwork that will be auctioned in May
disease ever in North America.
to support Alpha-1 research programs. Johnson and
Once a year, the family travels to St. Louis so pedihis kids participated, and his official NASCAR
atric liver specialist Jeffrey Teckman, MD, lead reFoundation video was shown on the Sprint screen
searcher in the Alpha-1 portion of the ChiLDREN
overlooking the track throughout the weekend.
study, can monitor Grace and Lucas.
“I’m just so thankful to Betty Jane France and
While Grace is close to normal, Lucas’ liver enzyme
NASCAR for giving me a platform to tell the
levels are three to four times above normal. “It gets
Alpha-1 story,” Johnson says. “We recently met parslightly worse every visit,” Johnson says.
ents of a 4-year-old who may need a liver transplant.
We are forever joined with them… This family now
Next to a photo of Lucas on his Facebook page,
knows there are other families out here. This camJohnson writes, “This is why I do what I do.” His
paign has allowed us to reach so many people, and I
charisma and ease with people have made him a
would love to be able to contribute to finding a cure.”
natural in both advocacy and campaigning, and his
supporters include fellow Jacksonville-area resident
Vote for Richard Johnson every day through Dec. 5 at
and X Factor TV show finalist Rion Paige, who also
NASCAR.com/award.
www.alpha-1foundation.org
5
FRONTIERS
6
The molecule
that changed
our world
What does the world owe
to Carl-Bertil Laurell?
A lot more than you think
n the 1960s, Robin Carrell got a medical
degree in his native New Zealand and
went to England’s prestigious Cambridge University on a fellowship to
study the pathology of hemoglobin – the protein
that carries oxygen in the blood.
Carrell’s PhD thesis was
about inherited conditions
like sickle cell anemia, the
classic genetic disease
found in African-Americans. When he presented
his research, “My senior
colleagues didn’t at first
believe my findings on familial anemia.”
The same kind of rejection
would come to him much
Robin Carrell
later in his research career,
and much more harshly.
“On nearly my last day at Cambridge,” Carrell says,
“I gave a lecture as part of a series sponsored by the
British Council.” At the end of his talk, he was approached by a young Norwegian medical researcher
named Magne Fagerhöl.
Fagerhöl had pioneered work on the Pi system,
which with later work by Canadian researcher
Diane Cox is still used today to describe the variations in the alpha-1 molecule. Their work is the
reason that Alphas describe themselves as being a
PiZZ or PiSZ genotype.
I
“Fagerhöl asked me, ‘Are you aware of the findings
in Malmo?’ Fagerhöl had been working with CarlBertil Laurell in Malmo and said he thought my research in hematology could be useful in the work
being done by Laurell’s group. It was that conversation with Fagerhöl that got me interested in studying Alpha-1.”
That was 1968, and Carrell was about to go home.
He did return, to the University of Canterbury in
Christchurch, New Zealand. But he also got in
touch with Laurell, received “enormous enthusiasm
from him,” and they decided to work together.
TEAMWORK AROUND THE WORLD
This began “an extraordinary collaboration, actually, right from one side of the earth to the other.”
The collaboration between Christchurch and
Malmo researchers – about 11,000 miles apart, in
the days before the Internet and email – went on for
decades. It was highly productive.
The two groups, sharing information freely, produced results that changed the world’s understanding of Alpha-1.
And also cystic fibrosis. And Creutzfeldt-Jacob (mad
cow) disease. And some forms of Parkinson’s. And
Huntington’s disease. And Alzheimer’s and some
other forms of dementia. And Down’s Syndrome.
Among others.
But all that was much later. In 1968, Robin Carrell
had just found out what he wanted to do with his
newly earned expertise in blood diseases: he wanted
to work with Laurell on Alpha-1 research.
“The first thing to do after getting back to New
Zealand was to set up a group. It took a while, and
then we set about identifying the sequence of alpha-1
antitrypsin. We focused on identifying the abnormalities in the common variant. Maurice Owen
made the first breakthrough, in identifying the S
mutation in 1975.”
Shortly after that, Laurell and his wife visited New
Zealand.
Maurice Owen recalls Laurell’s visit: “When we described the process by which we characterized the S
mutation, he seemed a bit taken aback. But he
brought our methods to Malmo when he returned.
Shortly after that, Jan-Olof Jeppsson identified the
Z mutation.”
1.877.2.CURE.A1 (228.7321)
THE ANTITRYPSIN TEAM — The team of New Zealand and Swedish researchers who collaborated for
decades to research Alpha-1. Maurice Owen of New Zealand, who identified the S mutation, is sitting at far left;
Jan-Olof Jeppsson of Malmo, Sweden, who identified the Z mutation, is standing at right. Robin Carrell is standing next to Jeppsson. The photo was taken in Christchurch, NZ, in 1980.
THE BIRTH OF THE SERPINS
“Now we were a team working together and the
aim was to identify the sequence of alpha-1 antitrypsin and understand its significance,” says Carrell.
“Once we had identified the sequence of antitrypsin, we realized it could be associated with another protein. Ross Boswell in our group showed
that antitrypsin could be aligned with antithrombin. This was the beginning of our understanding a
new family of proteins, what we called the birth of
the serpins.”
The new family they called the serpins built on the
earlier work of two researchers, Hunt and Dayhoff,
who in 1980 described "a surprising new protein
superfamily containing ovalbumin, antithrombinIII, and alpha-1 proteinase inhibitor."
Many more serpins have been identified since, and
Carrell is still researching them. He’s now emeritus
professor of hematology at Trinity College, Cambridge. He “retired” in 2003, but kept working in
research. “I’m still working in the field, but more
with other members of the serpin family,” he says.
www.alpha-1foundation.org
THE LANDMARK STUDY IN NATURE
In 1982 Carrell wrote to the scientific journal
Nature. He proposed to write a paper about the
group’s determining the sequence of the alpha-1
molecule. The editors replied with an invitation to
expand it to a 4-page review of the work if he could
write it in the next six weeks. “There was a lot of
communication between Malmo and Christchurch”
before the article, Structure and Variation of Human
Alpha-1 Antitrypsin was published. Carrell, a fairly
modest man, calls the paper “a landmark work.”
He provided the black-and-white photo published
here. It was taken in New Zealand in 1980; Carrell
says “this is the conjoint team that determined the
definitive ‘structure and variation of human alpha-1
antitrypsin’ published in Nature in 1982.”
The big question remained: How did the alpha-1
molecule work?
The tool used to find out is called X-ray crystallography: it uses X-rays to determine the structure of a
molecule in three dimensions.
In 1984, Laurell sent off some alpha-1 genetic ma-
7
FRONTIERS
terial to German crystallographer Robert Huber.
This began a 16-year effort to prove how the alpha1 protein destroyed the protease emitted by white
blood cells in the lungs. The protease is called neutrophil elastase, and when uncontrolled by the
alpha-1 protein, it damages lung tissue.
Huber crystallized (showed by X-ray crystallography) the three-dimensional structure of the alpha-1
molecule. “But this was after (the alpha-1 molecule) was spent. It had already interacted with the
protease. We needed the molecule before it acted on
the protease.”
Eventually, “Penny Stein (Penelope Stein, Carrell’s
first graduate student when he became a professor
at Cambridge) crystallized the first intact molecule,” says Carrell. “An extraordinary springlike action had taken place.”
So in 1991 Carrell published a paper that “presented the case for the idea that antitrypsin, and the
serpins in general, were all acting much like a
spring in a mousetrap. The evidence based on studies of abnormalities that caused dysfunction in disease was strong. I waited for the reaction from my
colleagues and the field in general. And when it
came, I can tell you it was absolutely catastrophic,
it was worse than unpleasant. They said that we’d
built our argument on medical freaks.”
Carrell had a problem. The critics were blistering
him. And he couldn’t prove them wrong.
MAKING THE MOLECULAR MOVIE
“Somehow we had to show what was happening in
antitrypsin at the atomic level in one millisecond.
And there’s only one way in microscopic crystallography that you can show something that’s beyond
any question at all, and that’s with structures, and
with moving structures that means a video. How
can you make a video that occurs at the atomic level
in one millisecond?”
His answer: “Daunting but not impossible. To
make a video, all you need are six or seven frozen
frames (of alpha-1 protein reacting to its protease).
We had the first and last frames (by Stein and
Huber). And in the year 2,000, the final critical
frame was solved by my colleague Jim Huntington.
With this we had the whole picture and we could
show the video.”
So he showed it. He calls it “15 years of work (1984
to 1999) in 15 seconds.”
8
Carrell dramatizes the video showing:
“And when we showed that, there was silence from
all the critics save one, and he stormed out of the
room and was never seen again. So it was a triumph for alpha-1 antitrypsin… and for Carl-Bertil
Laurell.”
(To see Prof. James Huntington’s video, see
http://tinyurl.com/serpins.)
THE CONFORMATIONAL DISEASES
David Lomas, now well known as an Alpha-1
physician and researcher, had joined the Cambridge
group as a research fellow in 1990.
In 1997, Carrell and Lomas published a paper in
The Lancet in which they used the title Conformational Diseases to propose a new category of diseases.
Carrell says the Lancet article discusses “the changes
that occur in the Alpha-1 S and Z mutations in cirrhosis, and how this provides a model for the
changes that occur in other diseases where proteins
aggregate and which result in a whole range of
pathologies, but in particular in the dementias. We
showed that there is a common feature. The common feature is a change in conformation (a change
in shape), where a protein that is normally stable,
when it changes shape, it self-aggregates (it clumps
or forms long chains) and it’s the aggregation
within the cell that causes the disease. If this aggregation occurs in the liver, the consequence is cirrhosis; if it occurs in the neurons (brain cells) the
consequence is dementia. That was argued in the
Lancet article, which has very much been taken up, I
think it was quoted something like 500 times.”
What makes Alpha-1 the prototype of conformational diseases?
“The structure of antitrypsin was done years before
antithrombin,” Carrell says. “With the structure of
antitrypsin, we were able to deduce the way that
heparin binds to antithrombin and inactivates it before we knew the structure of antithrombin. It was
the findings about antithrombin and the relationship between the two (antitrypsin and antithrombin) that convinced us that we were looking at a
family of proteins and not just a single stand-alone
protein. Antithrombin was essential to the recognition of the serpin family of protease inhibitors.”
Polymers – the long chains or clumps of proteins
that get stuck in the liver cell and cause Alpha-1 –
are typical in the many conformational diseases.
1.877.2.CURE.A1 (228.7321)
THE SZ TEAM — Jan-Olof Jeppsson, left, who identified the Alpha-1 Z mutation, and Maurice Owen,
right, who identified the S mutation, pose with Bob
Campbell of the Alpha-1 Foundation — who has both
an S and a Z mutation. They were attending the "50
Year Jubilee Symposium," a scientific conference on
the 50th anniversary of the discovery of Alpha-1, held
in Malmo, Sweden, in September. Eeva Piitulainen
headed the organizing committee for the event, which
was held in the same Malmo hospital where CarlBertil Laurell and Sten Eriksson worked when they
published the first paper on the landmark discovery in
1963. Eriksson was the honored guest.
SOME CARRELL OPINIONS
On augmentation therapy:
“Sadly, we can only justify giving replacement (augmentation) therapy after respiratory problems have
already developed. By that stage, (Alphas) are already beginning to lose elasticity in their lungs, so
that any change you can make by adding Alpha-1
replacement protein is going to be very difficult to
detect, because deterioration is well advanced, and
even under the best of circumstances, all you will
do is slow it down.
“The second point is that we are not at all sure that
the replacement of antitrypsin in the blood is sufficient to provide the antiprotease defense that is
needed in the connective tissue of the lung. I don’t
know anyone who doesn’t believe that we are looking at a problem as Jim Travis notably propounded,
of protease-antiprotease imbalance. But we all realize that this may be over-simplifying it. The problem is trying to prove it, and that has been very
disappointing to everyone.”
Nevertheless, he considers it “very sensible” for Alphas to take augmentation therapy if it is available to
them. “If I were in your shoes, I would do the same.”
www.alpha-1foundation.org
On the possibility of a cure for Alpha-1:
“Progress has been disappointing,” he says, on
Alpha-1 and on conformational diseases in general.
“As well as science, it’s going to require an element
of serendipity – someone who tries something that
works for the wrong reason.”
He points out that the discovery of Alpha-1 itself is
an example of serendipity – finding something
valuable seemingly by accident: A Swedish lung
specialist sent electrophoretic strips of the serum of
every one of his patients to Carl-Bertil Laurell in
the early 1960s; Laurell, looking at these strips,
found two strange samples with the alpha-1 protein
band missing on them; and then he asked Sten
Eriksson to do the study that led to their landmark
paper in 1963, announcing the discovery of Alpha-1
Antitrypsin Deficiency.
On Carl-Bertil Laurell:
“A measure of people of great ability is the type of
people they attract to them and the message that
they give them. The mark of Laurell's overwhelming contribution as a research leader is the way others in the group also made seminal contributions
that opened new fields of understanding – Larsson,
Ohlsson, Jeppsson, Sveger amongst others in Sweden, and my own group in New Zealand, amongst
others abroad.”
On the alpha-1 protein:
“Alpha-1 antitrypsin, because it has been so well
studied, has provided the paradigm, the template
model, for the changes that take place in the other
members of the (serpin) family. It’s become an industry; I think there’s now been 56,000 papers published based on the (serpin) family and how they
function. And it all started off with Carl-Bertil Laurell in Malmo, Sweden.” Carrell pauses and adds:
“And I like to think that I gave it a nudge along.”
Maurice Owen, a longtime member of Carrell’s research team in Christchurch, says that last statement
“is typical of (Carrell’s) modesty and understatement. He certainly gave it more than a nudge!”
In 2004, Carrell published a review in the first issue
of the journal COPD. The title was What the World
Owes to Alpha-1 Antitrypsin and to Carl-Bertil Laurell.
Today, an appropriate review might be called,
“What the World Owes to Alpha-1 Antitrypsin Deficiency and to Robin Carrell.”
9
FRONTIERS
Shorter wait lists.
Longer lives.
Respiratory therapist
Sharon McRee’s protocol
saves donor lungs for
life-saving transplants
or an Alpha with lung disease, sometimes a lung transplant is the only hope.
That’s a fact. Organ transplant wait lists
are another fact.
When these two facts combine, the only solution
appears to be this: make more donated lungs available for transplant.
One way to do that is to convince more people to
become organ donors. But there’s another complication:
most
donated in
lungs
they simply
is
study,
published
the are
Newunusable
England –Journal
of
don’t
function
well
enough.
What
if
more
of them
Medicine in 1987, used concentrated and purified
could beprotein
made usable
for pooled
transplant?
alpha-1
from the
blood plasma of
healthy
human
volunteers.
Made
by
Cutter Labs,
this
North Carolina respiratory care practitioner
Sharon
product
later became
Prolastin.
in 1988,
McRee figured
out exactly
how Launched
to accomplish
that.
Prolastin
first
augmentation
therapy
apAnd in thewas
lastthehalf
decade,
her idea has
dramatiproved
by the Food
and DrugofAdministration
(FDA).
cally increased
the number
lungs that can be
saved21
forAlphas
transplant.
“The
in this study were really pioneers, accepting
could
turnedwhen
out to
substantial
In 2007,what
McRee
washave
on duty
anbe
organ
risks
for augmentation
infusions,”
donor/trauma
patient was
broughtWewers
into thesays.
neurotrauma
intensive
unitthat
(ICU)
at Mission had
HospiThe
pivotal
studycare
found
augmentation
tal in Asheville,
NC. The patient
waswhich
brain-dead
demonstrated
“biochemical
efficacy,”
the
and could
not be
but the
lungs werethe
in prisFDA
accepted
as asaved,
rationale
for approving
drug
tine
condition
–
not
damaged
by
smoking,
disease,
in December, 1987.
or injury.article
However,
Wewers’
also the
saidpatient’s
it wouldpartial
take anoxygen
estimated
pressure
(PaO2)
was
plummeting.
PaO2 levels
300 to 500 Alphas in both arms ofLow
a doublewould disqualify
lungs
blinded
study for the
three
yearsfortotransplant.
show clear“They
levels of
would
be
deemed
‘poor
function’
even though
clinical effectiveness for augmentation
therapy.we
knew they were not,” says McRee.
“I still find it a difficult discussion with my Alpha-1
An organwhen
procurement
coordinator
for LifeShare
of
patients,
we talk about
the reasons
why they
the
Carolinas
was
present,
and
asked
McRee
if
she
might consider augmentation – since there’s still no
could that
remedy
proof
thisthe
willproblem.
slow down their loss of lung
“Before this,
brain-dead
were
put
function.
I believe
there patients
is no harm
innormally
augmentaon generic
settings,”harm.
McRee
tion,
other ventilation
than the economic
Thesaid.
cost“There
of inhad never
seemed to be a need to do more than that.
fusions
is high.”
F
Sharon McRee with a patient
In this case, we decided to use very aggressive settings, thinking that it might keep the lung functioning well enough to be viable for transplant.”
In addition to changing the ventilator settings,
McRee decided that repositioning the donor’s body
would also be beneficial. The weight of the lungs,
heart and chest wall can push down on the lower portion of the lungs and prevent the tiny air sacs in that
area from inflating, even when the ventilator is used.
“We also needed to simulate the effects of coughing
in order to keep secretions from building up in the
donor’s lungs and causing pneumonia,” McRee explained. “For that, we used a quad cough technique
– similar to a Heimlich maneuver.”
Thanks to this aggressive approach, the dead patient’s
lungs were saved for transplant. Suddenly, it became
clear to McRee that more donors’ lungs could be
saved – and be used for life-saving transplants.
She was on duty on several occasions when more
donors came into the ICU under similar circumstances – and she repeated the process each time.
WEWERS ON TODAY’S ALPHA-1
10
1.877.2.CURE.A1 (228.7321)
And sure enough, lungs that might have been unusable were procured for transplant.
“My ICU manager advised me to write down the
parameters I used so that other therapists would
know what to do,” she said. The result was the Mission Lung Donor Ventilator Management Protocol.
Why had no one done this before?
“In part, because no one knew the right questions
to ask,” said McRee. “Respiratory therapists weren’t
aware of the stringent PaO2 standards that were
vital for lung procurement. And LifeShare wasn’t
aware that respiratory therapists had ways to help
donor lungs meet those standards.”
The Mission protocol was eventually adopted by
LifeShare of the Carolinas and distributed to all 40
of their affiliated hospitals in North Carolina. It was
eventually adopted as a National Best Practice and
is now a standard of care for lung donors.
Nationally, about 18 percent – less than one in five
– of donor lungs are found suitable for transplant.
Since the Mission protocol has been adopted at the
40 member hospitals of LifeShare of the Carolinas,
that figure has been about 30 percent.
“Many hospitals may not be attuned to the needs of
lung procurement specialists,” said Thomas Kallstrom, executive director/CEO of the American Association for Respiratory Care. “This is an
important advancement. It’s especially significant
that this protocol was conceived and implemented
by a respiratory therapist.”
In recognition of her work, McRee has been given
awards by numerous national donor procurement
agencies. In 2012, the North Carolina Society of
Respiratory Care named her Respiratory Care Practitioner of the Year, and she has presented at national and international conventions.
Lung donation is McRee’s passion. “Lives are forever changed by the way we handle procurement,”
she said. “The entire Mission team works hard to
save donor lungs so they can be transplanted and
save lives. It’s a very big deal.
“We could more than double the number of available donor lungs across the U.S. if we use ventilators properly. Aggressive protocols like this could
annihilate lung wait lists if they were widely used.
That’s why I’m passionate about organ donation. If
you donate this precious gift of life to save others,
we need to do everything possible to make sure the
gift can be used. It’s that simple.”
www.alpha-1foundation.org
Lung allocation scores:
Are they fair to Alphas?
In 2005, the United Network for Organ Sharing (UNOS) and its parent organization, the
Organ Procurement and Transplantation Network (OPTN) implemented a new method of
allocating lungs for transplant. The new Lung
Allocation Scoring (LAS) System replaced the
previous method, under which a person who
had been longest on the list got priority over
sicker people who were much more in need of
a transplant.
How has the new system affected Alphas?
“Because the new system gives about twice as
much weight to a patient’s likelihood of dying
on the waitlist as it gives to their chances of
post-transplant survival, it has greatly benefited people with rapidly progressive lung disease,” said Robert Sandhaus, MD, PhD,
clinical director of the Alpha-1 Foundation.
“Alphas typically survive well even with severe lung disease. We wanted to see if they
were being adversely affected by the LAS.”
Sandhaus asked UNOS for the most recent data.
The results showed that transplants for Alphas
dropped under the new system – from 10 percent to below 4 percent of patients who get
lung transplants. The five-year post-transplant
survival rate for Alphas is 65 percent, better
than any group except lymphangioleiomyomatosis (LAM) patients. “But there are a small
number of LAM transplants and the recipients
tend to be young adult women,” Sandhaus said.
“This confirms what we already suspected,”
said Sandhaus. “Fewer Alphas are receiving
transplants, and Alphas do well in long-term
survival. These data do not fully explain the
small percentage of Alphas receiving transplants. Perhaps fewer Alphas need transplants
than in the past. More likely, the LAS unduly
penalizes Alphas because of the bias toward reducing waitlist mortality. Since fewer Alphas
get on the waiting list, it’s possible that some
of those not qualifying for transplant are
dying before even being listed. This missing
piece of the puzzle should be addressed.”
See more on Alphas and lung transplant
allocation in the spring Alpha-1-To-One.
11
ALPHA LIFE
12
A year to
Remember
A move for world action
in 50th anniversary year
mid the sights and sounds of the
Mediterranean coast and in the shadows
of the famed Gaudi cathedral, more than
250 Alphas, clinicians, researchers and
delegates from 23 countries gathered for the 4th International Alpha-1 Patient Congress in Barcelona.
The Congress, held in April, commemorated the
50th anniversary of the discovery of Alpha-1 by
Swedish researchers Carl-Bertil Laurell and Sten
Eriksson in 1963.
Alphas from around the world – from as far away as
Australia and New Zealand – talked about the
greatest needs for the Alphas in their own countries.
In a call to action that concluded the Congress, they
decided that the global Alpha-1 community needed
to unite their efforts to make a real change for
awareness and access to care. (See Global program director, page 13.)
Alongside the Congress, scientists met at the
Alpha-1 International Research Conference, which
for the first time focused on liver disease.
The Barcelona Congress was the flagship of the
many events marking the 50th anniversary of the
discovery of Alpha-1.
Later in April at the University of Massachusetts
Medical School, Ronald Crystal, MD, was honored
with the Sten Eriksson Distinguished Achievement
Award for spearheading the clinical trials that led to
the approval of augmentation therapy in 1987. The
event, in non-scientific language intended for a
general audience, included presentations by Crystal
and other Alpha-1 researchers, who spoke about
new treatments and research involving adult stem
cells, gene therapy, and advancements in augmentation therapy.
In June, Alphas gathered in Washington D.C. for
the Alpha-1 Association National Conference. In his
talk at the conference, Walsh presented a video sum-
A
Some anniversary year highlights, Clockwise from top
left: Team Alpha-1 at Escape to the Cape; special
guests at the Barcelona Congress; the New England
Celtic Connection; the George Washington Bridge
Walk; one of our three “Get the Scoop on Alpha-1”
events, this one in Iowa; Mark Brantly, MD, sees himself on an iPad video at the Alpha-1 Foundation's
“Mission Possible” both at the Alpha-1 Association’s
National Education Conference; Ronald Crystal, MD,
receives the Sten Eriksson Award from John Walsh.
mary of the Barcelona Congress to share the excitement and hope he saw in the international delegates.
Marilyn Black of New Zealand said it best: “I want
to go home and share the feeling that we belong to
a family of Alphas — that New Zealand isn’t just a
little group of people, isolated on their own. To get
everybody together and have a New Zealand-wide
organization – and world-wide!” (See the video at
http://www.alpha-1foundation.org/barcelona.)
In its 18th year, the September Escape to the Cape
bike trek around Cape Cod embodies the feeling
Black describes. Over the year, there were many
1.877.2.CURE.A1 (228.7321)
Global Initiative
director named
Building Friends for a Cure events, from walks
across historical landmarks to ice cream socials to
golf and croquet tournaments, but “the Escape” is
the granddaddy of them all. It is unique because it
brings together people from every segment of the
Alpha-1 community — Alphas, lung- and liver-affected, clinicians, researchers, the pharmaceutical
industry, friends and family.
In a way, Escape to the Cape is a microcosm of what
the 50th anniversary has done for the global Alpha-1
community. It has been the great Alpha-1 family
reunion: raising awareness, raising funds for research, and bringing Alphas together to let them
know they are not alone.
As the 50th anniversary year nears its close, we are
taking stock: What have we achieved this year, and
how will that improve life for generations of Alphas
to come? With your help, the Alpha-1 Foundation
will continue to fulfill its mission.
The Foundation has produced a short video of the
50th Anniversary Year in review (See the video at
www.alpha-1foundation.org/50th).
www.alpha-1foundation.org
Alpha-1 leaders ended the 4th International
Alpha-1 Patient Congress with a call to action: They would form an international working group to act on the needs they considered
most important. Their priorities were more
awareness of Alpha-1; access to treatment, especially augmentation therapy; and more testing, so that Alphas can be properly treated
without the usual years of delay in diagnosis.
At the Congress, the Alpha-1 Foundation offered its resources to help build a Web-based
communications platform for the global
Alpha-1 community. The goal: to connect
Alpha-1 organizations and individuals around
the world to work together on these priorities.
The Foundation has hired
Hillegonda (Gonny)
Gutierrez as Global Program
Director to help organize the
Alpha-1 community. Gutierrez is a Dutch citizen, now
living in Denver, CO, with
extensive project management and coalition-building
experience in the international not-for-profit
world.
A provisional steering committee of representatives from around the world is being formed
to choose the content of the global communications platform and to help develop a needs
assessment survey tool that can be used by
Alpha-1 communities anywhere.
Gutierrez will also help to build an advocacy
toolkit – to help improve access to care, including augmentation therapy – which may
be adapted for use by any country in their
own language. She will conduct educational
workshops with these countries to help with
effective use of the toolkit.
The Alpha-1 Foundation will act as a resource
for medical, public policy, and economic
health experts to build specific cases for presentation to health agencies and ministries.
For information about the Alpha-1 Global
Initiative, contact Gonny Gutierrez, ggutierrez
@alpha-1global.org or (305) 567-9888,
ext. 212.
13
One place.
All things Alpha.
CareZ is the place to go to find all of the
support you want to meet your specific needs.
With a comprehensive array of Alpha-1 support
services, we focus on the whole you and
provide a customizable community of care
built around your Alpha-1 and your life.
To find out more, contact
the CareZ community at:
1-888-415-2167
Monday-Friday, 8:00 AM to 5:00 PM CT
Please see Brief Summary of full Prescribing Information on following page.
CareZ is a registered trademark of CSL Behring LLC.
©2010 CSL Behring LLC
1020 First Avenue, PO Box 61501, King of Prussia, PA 19406-0901 USA
www.CSLBehring-us.com 09-ZMR-041 6/2010
Your home for Alpha-1 help
You are encouraged to report negative side effects of prescription drugs to the FDA.
Visit www.fda.gov/medwatch or call 1-800-FDA-1088.
ALPHA LIFE
16
The first
family of
augmentation
e is not famous. Today he is remembered
mostly by his family and friends.
But some former researchers at the National Institutes of Health (NIH) still
keep a photo of A.J. Mosley making history. The
photo shows A.J. receiving the first infusion in the
clinical trial that won approval of augmentation
therapy – still the only specific therapy for Alpha1-related lung disease.
In his early 50s, A.J. was diagnosed with emphysema. He had never smoked; he exercised every day.
“The diagnosis was a real shock,” says Mosley’s son
James, 63. A few years later, A.J. was diagnosed
with Alpha-1 and told it was hereditary. He insisted
that his sons, James, Jerry, and Phil, be tested.
“We were all a little uneasy,” James says. “We were
told that we each had a 25 percent chance of having
Alpha-1. And then all three of us were diagnosed as
Alphas. I guess we ‘beat the odds’ so to speak.”
A.J. worried about his sons. “Our dad was more
concerned about us than with his own health – he
would have done anything to help find a cure for
this disorder,” says James. So when A.J. found out
about a study for Alpha-1 patients, he was soon on
his way to the National Institutes of Health (NIH)
in Bethesda, MD.
Mark Wewers, MD, conducted the study, in which
Alpha-1 patients received infusions of purified
alpha-1 protein, hoping to increase the protein in
the lungs to a level high enough to be protective
and slow the loss of lung tissue.
“The 21 Alphas in this study were really pioneers,
accepting what could have turned out to be substantial risks for augmentation infusions,” Wewers
said in 2011.
“I’m not sure how my Dad became the first patient
to receive an infusion but he probably insisted that
he be first,” James says. “Dad only thought about
H
all the good he was going to do for others, mainly
us boys. But it was scary for us—we were well
aware of the risks.”
A.J. moved to Bethesda for six months, received a
weekly infusion, and underwent constant testing.
The New England Journal of Medicine published the
article based on this study in April, 1987. To the
surprise of many, the Food and Drug Administration (FDA), approved the new therapy in December, 1987 and the first infusion product, Prolastin,
became available in early 1988.
James and his brothers joined the FDA-required
Phase 4 study of 1,129 Alphas from 1989-96. The
Mosleys became the first family of augmentation.
A.J. remained on augmentation therapy. “It really
slowed down the lung deterioration nicely,” James
says. “Dad stayed on it religiously for 10 years.”
A.J. and Mary Frances Mosley in 1987. Behind them,
from left, Buford (Phil), Jerry and James.
But in the late 1990s, A.J.’s lungs had deteriorated,
and he had lung volume reduction surgery. His
breathing improved dramatically for several years
until 2001, when he began to have constant lung infections. A.J. died at 74 on Valentine’s Day, 2002.
James had a lung transplant in 2012. After a long
year of battling infections and complications, he’s
doing much better. Phil and Jerry are in good
health, with little to no lung deterioration. All the
Mosleys are from Mobile, AL.
“I hope I’ve been a good example to you boys,” were
A.J.’s last words to James. “Of course I told him
that he was,” James says. “He was the most wonderful man I've ever known.”
1.877.2.CURE.A1 (228.7321)
esidents in 25 states may soon face
higher insurance premiums and health
care costs, if the governments of those
states continue to refuse participation
in a critical part of the Affordable Care Act (ACA)
or Obamacare.
Under the ACA, the Medicaid program will be expanded to include as many as 21 million low-income individuals and families. This will provide
health care coverage for the “working poor” who
have traditionally not been eligible for Medicaid,
a joint federal and state government health care
program.
Legislators in 25 states are currently refusing to participate in this expansion, even though the federal
government will finance 100 percent of the expansion through 2016 and 90 to 95 percent of the expansion through 2022.
“Hospitals in these states will have to continue to
do business as usual, treating many of these uninsured residents in their Emergency Departments
rather than in primary care settings,” says Miriam
O’Day, senior director of public policy for the
Alpha-1 Foundation. “Hospitals have lobbied hard
for the Medicaid expansion.”
Treating uninsured patients for all their health care
needs in the Emergency Department is the most expensive way possible, resulting in billions of dollars
of unpaid hospital bills each year. These unpaid
bills raise health care costs for everyone else.
Each state has different eligibility requirements for
its Medicaid program, which traditionally provides
health care coverage for the very poor – mostly children and families, disabled and elderly in nursing
homes. In some states Medicaid has only provided
health care coverage for individuals with incomes as
low as half the federal poverty level.
However, under the ACA, eligibility for Medicaid
in all states would be expanded in 2014 to include
anyone whose income is at or below 138 percent of
the federal poverty level ($23,550 for a family of
four in 2014). Even with subsidies, the insurance
R
www.alpha-1foundation.org
States Choosing to NOT Participate in the
Affordable Care Act Medicaid Expansion
Program as of Oct. 30, 2013:
Alabama
New Hampshire
Alaska
North Carolina
Florida
Oklahoma
Georgia
Pennsylvania
Idaho
South Carolina
Indiana
South Dakota
Kansas
Tennessee
Louisiana
Texas
Maine
Utah
Mississippi
Virginia
Missouri
Wisconsin
Montana
Wyoming
IN YOUR INTEREST
Medicaid Expansion:
Good news, bad news
plans offered in the new health care marketplaces
are out of reach for those with income as low as 138
percent of federal poverty level.
“With the Medicaid expansion and other coverage
provisions in the ACA, the number of uninsured [in
America] would be cut by 48 percent,” according to
the Urban Institute and the Kaiser Commission on
Medicaid and the Uninsured, (a part of the Kaiser
Family Foundation, a non-profit foundation focused
on major health care issues).
Greatly reducing the number of uninsured people
reduces or eliminates the effect of unpaid hospital
bills being passed on to others in the form of higher
health costs and higher insurance premiums.
The 25 states now rejecting Medicaid expansion
have about 5 million people who would have been
covered by the program. They still have until January 2014 to decide to participate in the expansion
program. “President Obama’s administration has
left the door open—these states could still change
their minds without any penalty,” O’Day says. “So I
predict the majority will change their minds and decide to expand Medicaid eligibility in their state.”
Nebraska
17
IN ALPHA-1 ANTITRYPSIN (AAT)
AUGMENTATION
EXPERIENCE
THE LIQUID
THE FIRST
DIFFERENCE
AND ONLY
OF LIQUID GLASSIA
READY-TO-INFUSE
1-4
BENEFITS OF LIQUID GLASSIA:
• Fewer steps—no reconstitution required1
• Safety considerations—reduces the chance for preparation errors1,5
ASK YOUR DOCTOR TODAY IF LIQUID GLASSIA IS RIGHT FOR YOU.
INDICATION FOR GLASSIA [ALPHA1-PROTEINASE INHIBITOR (HUMAN)]
GLASSIA is for adults who have an inherited deficiency of alpha-1 antitrypsin (Alpha-1) and emphysema. GLASSIA is used to
replace the alpha-1 protein that is deficient. The effect of Alpha1 protein replacement with GLASSIA on pulmonary exacerbations
and on the progression of emphysema has not been shown in clinical studies.
• The long term effects of chronic replacement therapy of patients with GLASSIA treatment are not available.
• GLASSIA is not for use in patients with lung disease who do not have the diagnosis of Alpha-1.
DETAILED IMPORTANT RISK INFORMATION FOR GLASSIA
GLASSIA should not be used by patients with an IgA deficiency due to the risk of severe allergic reactions.
GLASSIA should not be used by patients with a history of severe allergic reactions to other Alpha-1 products.
Early signs of an allergic reaction to GLASSIA may include hives, itching, chest tightness, shortness of breath, faintness, low
blood pressure, and anaphylaxis. If any of these symptoms occur, stop the infusion immediately and contact your
healthcare provider or call emergency services.
GLASSIA is made from human plasma and may contain infectious agents that can cause disease, for example, viruses and
theoretically, the Creutzfeldt-Jakob disease (CJD) agent.
GLASSIA should be infused at room temperature within three (3) hours after entering the vial and should be given alone.
Do not mix GLASSIA with other medicines.
Safety and effectiveness in patients over 65 years of age have not been established.
In clinical studies, the most common adverse reactions reported in at least 5% of subjects receiving GLASSIA were headache
and dizziness.
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch
or call 1-800-FDA-1088.
Please see Brief Summary of Full Prescribing Information on the adjacent page.
References: 1. GLASSIA [Alpha1-Proteinase Inhibitor (Human)] Prescribing Information. Westlake Village, CA: Baxter Healthcare Corporation; June 2012. 2. ZEMAIRA [Alpha1-Proteinase Inhibitor
(Human)] Prescribing Information. CSL Behring, LLC: Kankakee, IL; April 2013. 3. ARALAST NP [Alpha1-Proteinase Inhibitor (Human)] Prescribing Information. Baxter Healthcare Corporation: Westlake
Village, CA; April 2010. 4. PROLASTIN-C [Alpha1-Proteinase Inhibitor (Human)] Prescribing Information. Talecris Biotherapeutics, Inc: Research Triangle Park, NC; January 2013. 5. ASHP guidelines on
preventing medication errors in hospitals. American Society of Health System Pharmacists Web site. http://www.ashp org/s_ashp/docs/files/MedMis_Gdl_Hosp.pdf. Accessed June 18, 2013.
Baxter is a registered trademark of Baxter International Inc. Glassia is a registered trademark of Kamada Ltd.
October 2013
USBS341130002
Adverse Reactions1 Occurring in > 5% of Subjects
During the First 12 Weeks of Treatment
GLASSIA [Alpha1-Proteinase Inhibitor (Human)]
Brief Summary of Prescribing Information. Please see package insert
for full prescribing information.
INDICATIONS AND USAGE
Prolastin
No. of subjects: 17
No. of subjects with
adverse reactions1
(AR) (percentage of
all subjects)
No. of subjects with
adverse reactions1
(AR) (percentage of
all subjects)
Cough
3 (9%)
4 (24%)
Upper respiratory tract
infection
3 (9%)
0 (0%)
Headache
3 (9%)
3 (18%)
Sinusitis
2 (6%)
1 (6%)
Chest discomfort
2 (6%)
0 (0%)
Dizziness
2 (6%)
0 (0%)
Hepatic enzyme
increased
2 (6%)
0 (0%)
Adverse Event (AE)
Alpha1-Proteinase Inhibitor (Human), GLASSIA is indicated for chronic
augmentation and maintenance therapy in adults with emphysema due to
DPOHFOJUBMEFmDJFODZPGBMQIB1-proteinase inhibitor (Alpha1-PI), also known
as alpha1BOUJUSZQTJO""5
EFmDJFODZ
• The effect of augmentation therapy with GLASSIA or any Alpha1-PI product
on pulmonary exacerbations and on the progression of emphysema in
Alpha11*EFmDJFODZIBTOPUCFFOEFNPOTUSBUFEJOSBOEPNJ[FEDPOUSPMMFE
DMJOJDBMUSJBMT
• Clinical data demonstrating the long-term effects of chronic augmentation
BOENBJOUFOBODFUIFSBQZPGJOEJWJEVBMTXJUI(-"44*"BSFOPUBWBJMBCMF
• GLASSIA is not indicated as therapy for lung disease in patients in whom
severe Alpha11*EFmDJFODZIBTOPUCFFOFTUBCMJTIFE
DOSAGE AND ADMINISTRATION
• For Intravenous Use Only.
• 6TFBTFQUJDUFDIOJRVFGPSBMMQSFQBSBUJPOBOEBENJOJTUSBUJPOTUFQT
• *OTQFDUUIFWJBMPG(-"44*"5IFTPMVUJPOTIPVMECFDMFBSBOEDPMPSMFTT
UPZFMMPXHSFFOBOENBZDPOUBJOBGFXQSPUFJOQBSUJDMFT%POPUVTFJGUIF
QSPEVDUJTDMPVEZ
• "ENJOJTUFS(-"44*"BMPOFEPOPUNJYXJUIPUIFSBHFOUTPSEJMVUJOHTPMVUJPOT
• Administer product brought to room temperature within three hours of
FOUFSJOHUIFWJBMT
GLASSIA
No. of subjects: 33
1
An adverse reaction is any adverse event which met any of the following criteria:
(a) an adverse event that began within 72 hours following the end of product infusion,
or (b) an adverse event considered by either the investigator or sponsor to be at least
possibly related to product administration, or (c) an adverse event for which causality
BTTFTTNFOUXBTNJTTJOHPSJOEFUFSNJOBUF
Treatment of Congenital Alpha13URWHLQDVH,QKLELWRU'HÀFLHQF\
The recommended dosage of GLASSIA is 60 mg/kg body weight
BENJOJTUFSFEPODFXFFLMZCZJOUSBWFOPVTJOGVTJPO%PTFSBOHJOHTUVEJFT
VTJOHFGmDBDZFOEQPJOUTIBWFOPUCFFOQFSGPSNFE5IFSFDPNNFOEFE
EPTBHFPGNHLHUBLFTBQQSPYJNBUFMZNJOVUFTUPJOGVTF5IF
JOGVTJPOSBUFTIPVMEOPUFYDFFEN-LHCPEZXFJHIUQFSNJOVUF
Postmarketing Experience
5IFGPMMPXJOHSFBDUJPOTIBWFCFFOJEFOUJmFEEVSJOHQPTUNBSLFUJOHVTFPG
(-"44*"JODMJOJDBMQSBDUJDF#FDBVTFUIFZBSFSFQPSUFEWPMVOUBSJMZGSPN
BQPQVMBUJPOPGVOLOPXOTJ[FFTUJNBUFTPGGSFRVFODZDBOOPUCFNBEF
The reactions, which have been chosen for inclusion due to either their
seriousness, frequency of reporting, possible causal connection to GLASSIA,
PSBDPNCJOBUJPOPGUIFTFGBDUPSTJODMVEF)FBEBDIF%ZTQOFB'BUJHVF
BOE/BVTFB
CONTRAINDICATIONS
USE IN SPECIFIC POPULATIONS
(-"44*"JTDPOUSBJOEJDBUFEJOJNNVOPHMPCVMJO"*H"
EFmDJFOUQBUJFOUTXJUI
BOUJCPEJFTBHBJOTU*H"
Pregnancy
Pregnancy Category C
GLASSIA is contraindicated in individuals with a history of severe immediate
hypersensitivity reactions, including anaphylaxis, to Alpha11*QSPEVDUT
"OJNBMSFQSPEVDUJPOTUVEJFTIBWFOPUCFFODPOEVDUFEXJUI(-"44*"*UJT
also not known whether GLASSIA can cause fetal harm when administered
UPQSFHOBOUXPNFOPSDBOBGGFDUSFQSPEVDUJWFDBQBDJUZ(-"44*"TIPVMECF
HJWFOUPBQSFHOBOUXPNBOPOMZJGDMFBSMZOFFEFE
WARNINGS AND PRECAUTIONS
Hypersensitivity to IgA
(-"44*"NBZDPOUBJOUSBDFBNPVOUTPG*H"1BUJFOUTXJUITFMFDUJWFPSTFWFSF
*H"EFmDJFODZBOEXJUILOPXOBOUJCPEJFTUP*H"IBWFBHSFBUFSSJTLPG
EFWFMPQJOHTFWFSFIZQFSTFOTJUJWJUZBOEBOBQIZMBDUJDSFBDUJPOT.POJUPSWJUBM
TJHOTDPOUJOVPVTMZBOEPCTFSWFUIFQBUJFOUDBSFGVMMZUISPVHIPVUUIFJOGVTJPO
IF ANAPHYLACTIC OR SEVERE ANAPHYLACTOID REACTIONS OCCUR,
DISCONTINUE THE INFUSION IMMEDIATELY. Have epinephrine and
other appropriate supportive therapy available for the treatment of any acute
BOBQIZMBDUJDPSBOBQIZMBDUPJESFBDUJPO
Transmissible Infectious Agents
Because this product is made from human plasma, it may carry a risk
of transmitting infectious agents, such as viruses, and theoretically, the
$SFVU[GFMEU+BLPCEJTFBTF$+%
BHFOU5IFSJTLPGUSBOTNJUUJOHBOJOGFDUJPVT
BHFOUIBTCFFONJOJNJ[FECZTDSFFOJOHQMBTNBEPOPSTGPSQSJPSFYQPTVSFUP
certain viruses, by testing for the presence of certain current virus infections
and by inactivating and removing certain viruses during the manufacturing
process (see Description [11] in full prescribing information for viral reduction
NFBTVSFT
%FTQJUFUIFTFNFBTVSFTTVDIQSPEVDUTNBZTUJMMQPUFOUJBMMZ
USBOTNJUIVNBOQBUIPHFOJDBHFOUT5IFSFJTBMTPUIFQPTTJCJMJUZUIBUVOLOPXO
JOGFDUJPVTBHFOUTNBZCFQSFTFOUJOTVDIQSPEVDUT
5IFQIZTJDJBOTIPVMEXFJHIUIFSJTLTBOECFOFmUTPGUIFVTFPGUIJTQSPEVDU
BOEEJTDVTTUIFSJTLTBOECFOFmUTXJUIUIFQBUJFOU
All infections thought by a physician possibly to have been transmitted
by this product should be reported by the physician or other healthcare
provider to Kamada Ltd. at 1-866-GLASSIA or FDA at 1-800-FDA-1088 or
www.fda.gov/medwatch.
No seroconversions for hepatitis B or C (HBV or HCV) or human
JNNVOPEFmDJFODZWJSVT)*7
PSBOZPUIFSLOPXOJOGFDUJPVTBHFOUXFSF
SFQPSUFEXJUIUIFVTFPG(-"44*"EVSJOHUIFDMJOJDBMTUVEJFT
ADVERSE REACTIONS
The serious adverse reaction observed during clinical studies with GLASSIA
XBTFYBDFSCBUJPOPGDISPOJDPCTUSVDUJWFQVMNPOBSZEJTFBTF$01%
The most common drug-related adverse reactions considered by the
investigator to be at least possibly related to GLASSIA administration observed
BUBSBUFPGJOTVCKFDUTSFDFJWJOH(-"44*"XFSFIFBEBDIFBOEEJ[[JOFTT
Nursing Mothers
It is not known whether Alpha11*JTFYDSFUFEJOIVNBONJML#FDBVTFNBOZ
drugs are excreted in human milk, caution should be exercised when GLASSIA
JTBENJOJTUFSFEUPBOVSTJOHXPNBO
Pediatric Use
4BGFUZBOEFGGFDUJWFOFTTJOQFEJBUSJDQBUJFOUTIBWFOPUCFFOFTUBCMJTIFE
Geriatric Use
Clinical studies of GLASSIA included 11 subjects of 65 years of age or
PMEFS5IJTOVNCFSPGTVCKFDUTXBTOPUTVGmDJFOUUPEFUFSNJOFXIFUIFSUIFZ
SFTQPOEEJGGFSFOUMZGSPNZPVOHFSTVCKFDUT"TGPSBMMQBUJFOUTEPTJOHGPS
HFSJBUSJDQBUJFOUTTIPVMECFBQQSPQSJBUFUPUIFJSPWFSBMMTJUVBUJPO4BGFUZBOE
FGGFDUJWFOFTTJOQBUJFOUTPWFSZFBSTPGBHFIBWFOPUCFFOFTUBCMJTIFE
PATIENT COUNSELING INFORMATION
• Inform patients of the early signs of hypersensitivity reactions, including
IJWFTHFOFSBMJ[FEVSUJDBSJBDIFTUUJHIUOFTTEZTQOFBXIFF[JOHGBJOUOFTT
IZQPUFOTJPOBOEBOBQIZMBYJT"EWJTFQBUJFOUTUPEJTDPOUJOVFVTFPGUIF
product and contact their physician and/or seek immediate emergency care,
EFQFOEJOHPOUIFTFWFSJUZPGUIFSFBDUJPOJGUIFTFTZNQUPNTPDDVS
• Inform patients that GLASSIA is made from human plasma and may contain
JOGFDUJPVTBHFOUTUIBUDBODBVTFEJTFBTFFHWJSVTFTBOEUIFPSFUJDBMMZ
UIF$+%BHFOU
&YQMBJOUIBUUIFSJTLPG(-"44*"USBOTNJUUJOHBOJOGFDUJPVT
agent has been reduced by screening the plasma donors, by testing the
donated plasma for certain virus infections, and by a process demonstrated
to inactivate and/or remove certain viruses during manufacturing (see
Warnings and Precautions
4ZNQUPNTPGBQPTTJCMFWJSVTJOGFDUJPOJODMVEF
headache, fever, nausea, vomiting, weakness, malaise, diarrhea, or, in the
DBTFPGIFQBUJUJTKBVOEJDF
• Inform patients that administration of GLASSIA has been demonstrated to
raise the plasma level of Alpha1-PI, but that the effect of this augmentation on
the frequency of pulmonary exacerbations and on the rate of progression of
FNQIZTFNBIBTOPUCFFOFTUBCMJTIFECZDMJOJDBMUSJBMT
#BYUFSJTBSFHJTUFSFEUSBEFNBSLPG#BYUFS*OUFSOBUJPOBM*OD
(MBTTJBJTBSFHJTUFSFEUSBEFNBSLPG,BNBEB-UE
Baxter Healthcare Corporation, Westlake Village, CA 91362 USA
*TTVFE0DUPCFS64#4
ALPHA 411
20
Social media
ambassadors
for Alpha-1
ith a little time, work, and commitment,
hundreds of members of the Alpha-1
community have become Alpha-1 awareness ambassadors via social media. They
increase awareness about Alpha-1 worldwide,
connecting Alphas to Alpha-1 programs, websites,
e-newsletters, support groups and more.
Here are comments from some of these “social
media ambassadors.”
Julie Knutson from Minnesota:
“I have met approximately 400 people
online affected by Alpha-1. On my
Facebook newsfeed, I post information
relating to transplantation, organ
and plasma donation, advocacy, my
Alpha-1 experience, research, stories
about Alpha-1 awareness and more.
During Alpha-1 Awareness month in November, I post
information from the Alpha-1 Association's ‘Awareness’
web portal located at the ‘community’ tab at alpha1.org. I
like to encourage testing so my friends online do not have
to go through what I went through. When I was diagnosed, my lung capacity was 38%. My doctor dropped the
ball. I feel like raising awareness using social media is a
good way for me to create change and build upon my online relationships. Moreover, on Facebook, I created the
‘Alpha-1 Sisters’ group; 147 women belong to this safe
and loving group and we all make it a point to share and
spread information about Alpha-1.”
Valerie Hale from Maine: “On
Facebook, I belong to the Alpha-1
Genies Group, the Alpha-1 Group,
the Alpha-1 Sisters Group, the U.K.
Support Group and the Alpha-1
Kids Group. Not only do I post information on my newsfeed, but I share
information in these groups too. I
share links to Alpha-1 news stories, stories about my
Alpha-1 journey, awareness articles, Alpha-1 Association
virtual telecalls and more. During Alpha-1 Awareness
month, I am going to insert an Alpha-1 Awareness cover
W
photo on my personal profile and post links relating to
Alpha-1 awareness that are sent to me ether by the
Alpha-1 Association and Alpha-1 Foundation. I have
739 Facebook friends, 400 of them affected by Alpha-1.
I may not see all these contacts on a regular basis, but social media allows the Alpha-1 Community to applaud
and congratulate each other. It is a positive force.”
Tam Lyions from Nebraska:
“Awareness about Alpha-1 and
organ donation is important to me as
it can help people become diagnosed
earlier, allowing them to get the support they need. It can also help doctors
with early detection. During and
after Alpha-1 Awareness month in
November, I will continue to share whatever Alpha-1
news comes my way via e-mail and online. Facebook is a
way for me to give and receive inspiration and support
from the Alpha-1 community. About 70 people usually
share or ‘like’ my Alpha-1 posts daily. It is amazing to
think of all the impressions and reach I have generated.”
For more information on how you can get involved
in spreading awareness about Alpha-1 both during
Alpha-1 Awareness month and all year long, please
visit the ‘Alpha-1 Awareness’ web portal under the
‘Community’ tab at alpha1.org.
Leave an Alpha-1 Legacy
All of us appreciate gifts. Sometimes the gift you prefer might
be a gift to the Alpha-1 Foundation. You can ask family and
friends to designate the Foundation for memorial gifts, birthday
celebrations, anniversaries or births.
You may also wish to name the
Alpha-1 Foundation in your will. You
can combine your desire to give to
Alpha-1 research with your overall
financial, tax and estate planning goals. You
will help those touched by Alpha-1
now and for years to come.
For information,
contact Angela McBride at
888-825-7421, ext. 233 or
[email protected].
Research for a Cure
1.877.2.CURE.A1 (228.7321)
A life spent
helping people
usan Clarke has devoted her life to people who need help.
Even before becoming an AlphaNet coordinator, “I’d always done a lot of volunteering,” says Clarke. Among other things, as a
stay-at-home mom, she was district chairman of the
Boy Scouts for seven years and vigil member of the
organization’s Order of the Arrow.
Clarke was diagnosed with allergies and asthma
long before discovering that her coughing, wheezing, and shortness of breath were actually caused by
Alpha-1. Her coughing problems began after she
moved to New Hampshire in 1995 with her five
children. Her doctor diagnosed her with asthma.
“I was coughing so much
that I couldn’t speak a full
sentence,” says Clarke.
Later, a CT scan showed
that she had emphysema, a
surprise to Clarke because
she had never smoked. She
was determined to find an
explanation.
After doing some research
on emphysema, Clarke
Susan Clarke
learned about Alpha-1.
When she suggested Alpha-1 to her physician, he
dismissed it as even a possibility. He did send her to
a pulmonologist, however.
“I was tested and prescribed infusions without ever
being told that I did have Alpha-1 – and I was even
a ZZ,” she says. A call from her augmentation therapy provider looking to confirm insurance information was the first time she heard the correct
diagnosis.
“When you first find out, you start counting down
to when you’re going to die,” says Clarke. But Vicki
Cameron, her AlphaNet coordinator, changed that.
“It was like someone was holding a hand out to a
drowning person,” she says.
S
www.alpha-1foundation.org
After starting augmentation therapy, Clarke noticed
an unexpected but wonderful bonus: immediate
improvement in her health as well. “I am very fortunate,” she says. “I can do almost everything, just
more slowly!”
Clarke lives with two of her sons, Gwilym and
Gareth, and two dogs in Hampstead, New Hampshire. Her other three children are Michael, who
lives in England, Caroline, who lives in New York,
and Natalie, who lives in Derry, New Hampshire.
Clarke’s first granddaughter was born last October,
and she is expecting her second this Christmas.
Now, as an at-large AlphaNet coordinator, Clarke is
able to help improve the lives of others around the
country who face the difficulties of living with
Alpha-1. “It’s an opportunity to encourage people
and have people encourage you.” She calls her fellow coordinators her “AlphaNet family.”
Besides her years of volunteer work, she has another major asset: she has post-graduate training in
guidance and counseling. “It meant so much to me
to get that support when I was first diagnosed,”
she says, “and I wanted to be that support for
someone else.”
As she says herself, for Susan Clarke, becoming a coordinator was “a perfect fit.”
&
%$ "
$
#
#
'$
"
$
" $ !%
'
$ "
#
$
## #$
$
$+#
$
#( & # $ )
( ( %
#
%#$
& $ "
"#*
$
"
$ ' "
& "
($
$
(
"
"
$ "( #
"
%#
21
ALPHA 411
Calendar of Events 2014
What?
Education Day
When?
Feb. 22
Where?
San Francisco, CA
Celtic Connection
Mar. 8
Boston, MA
Education Day
Mar. 22
Dallas, TX
Education Day
Apr. 12
Jacksonville, FL
Golf for a Cure
Apr. 14
Jacksonville, FL
Hero Walk
Apr. 26
Henrico, VA
George Washington Bridge Walk
May 10
NY – NJ
Get the Scoop on Alpha-1
Jul. 27
Johnston, IA
Alpha-1 Walk / Get the Scoop
Aug. TBD
Denver, CO
Education Day
Aug. 23
Boston, MA
Escape to the Cape Bike Trek
Sept. 26-28
Cape Cod, MA
Education Day
Oct. 11
St. Louis, MO
Step Forward for Alpha-1 Walk
Nov. 8
WPB, FL
Las Vegas Rocks
Dec. 11
Las Vegas, NV
Education Day
Dec. 13
Las Vegas, NV
Who?
Alexis Artiles
[email protected]
Bob Healy
[email protected]
Alexis Artiles
[email protected]
Alexis Artiles
[email protected]
Sarah Johnson
[email protected]
Pam Van Scoy
[email protected]
Joe Reidy
[email protected]
Peg Iverson
[email protected]
Angela McBride
[email protected]
Alexis Artiles
[email protected]
Angela McBride
[email protected]
Alexis Artiles
[email protected]
Gordon Cadwgan
[email protected]
Angela McBride
[email protected]
Alexis Artiles
[email protected]
For fundraising event information, contact Angela McBride at (877) 228-7321 ext 233 or [email protected].
For Education Days information, contact Alexis Artiles at (800) 521-3025 ext. 310 or [email protected].
Some 50th anniversary events
AlphaNet CEO Robert Barrett and Foundation board member Kenneth Irvine
at Irvine's Alpha-1 Golf Tournament in Greenwich, CT; Friends of Get the Scoop
on Alpha-1 in Fairmont, MN; Terry Nickerson and friend at the Alpha-1 Walk in
South Bend, IN. (Story and more photos, page 12)
22
1.877.2.CURE.A1 (228.7321)
PROLASTIN®-C
----------------CONTRAINDICATIONS --------------
Alpha1-Proteinase Inhibitor
(Human)
IgA
deficient
patients
with
antibodies
against IgA.
HIGHLIGHTS OF PRESCRIBING INFORMATION
---------WARNINGS AND PRECAUTIONS -------
These highlights do not include all the
7 " 5$ ).+.$ ).-1$.#).$*$ -"$)-.
information needed to use PROLASTIN®-C
IgA are at greater risk of developing severe
(Alpha1-Proteinase Inhibitor [Human]) safely
hypersensitivity and anaphylactic reactions.
and
effectively.
See
full
prescribing
7 #$- +,*/. $- ( !,*( #/() +'-(
information for PROLASTIN-C.
and may contain infectious agents, e.g.,
PROLASTIN®-C (Alpha1-Proteinase Inhibitor
viruses and, theoretically, the Creutzfeldt-
[Human]) Lyophilized Preparation
Jakob disease agent.
----------------ADVERSE REACTIONS--------------
For Intravenous Use Only
The most common drug related adverse
Initial U.S. Approval: 1987
reactions during clinical trials in 1% of
-------------INDICATIONS AND USAGE -----------
subjects were chills, malaise, headache, rash,
hot flush, and pruritus.
PROLASTIN-C is an alpha1-proteinase inhibitor
that is indicated for chronic augmentation and
maintenance therapy in adults with emphysema
due to deficiency of alpha1-proteinase inhibitor
(alpha1-antitrypsin deficiency). The effect of
augmentation
therapy
with
any
alpha1-
proteinase inhibitor (Alpha1-PI) on pulmonary
exacerbations and on the progression of
To report SUSPECTED ADVERSE REACTIONS,
contact Grifols Therapeutics Inc. at 1-800520-2807 or FDA at 1-800-FDA-1088 or
www.fda.gov/medwatch.
---------USE IN SPECIFIC POPULATIONS ------7 , "))3 * #/() *, )$(' . only if clearly needed.
emphysema in alpha1-antitrypsin deficiency has
not
been
demonstrated
in
randomized,
controlled clinical trials. PROLASTIN-C is not
indicated as therapy for lung disease in patients
in whom severe Alpha1-PI deficiency has not
been established.
Grifols Therapeutics Inc.
- ,#,$)"' ,&
$ )- *
08941114-BS
Revised: June 2012
25 YEARS MAKES US
ALPHA-1 EXPERTS
OUR COMMITMENT MAKES
US PROLASTIN C
®
ALPHA1- PROTEINASE INHIBITOR (HUMAN)
Our commitment extends beyond PROLASTIN®-C (Alpha1-Proteinase Inhibitor [Human]), the #1 prescribed
augmentation therapy for alpha1-antitrypsin deficiency.1 There’s also PROLASTIN DIRECT®, a comprehensive
patient support program that provides access to alpha-1 insurance experts, a dedicated alpha-1 pharmacy, and a
national network of alpha-1–certified infusion nurses. PROLASTIN DIRECT offers the only alpha-1 disease
management program with proven patient outcomes2—and it’s the only place to order PROLASTIN-C.
PROLASTIN C
For more information, call 1-800-305-7881
or visit www.prolastin.com.
IMPORTANT SAFETY INFORMATION
PROLASTIN-C, Alpha1-Proteinase Inhibitor (Human) is indicated for chronic
augmentation and maintenance therapy in adults with emphysema due to
deficiency of alpha1-proteinase inhibitor (alpha1-antitrypsin deficiency).
The effect of augmentation therapy with any alpha1-proteinase inhibitor
(alpha 1-PI) on pulmonary exacerbations and on the progression of
emphysema in alpha1-antitrypsin deficiency has not been demonstrated
in randomized, controlled clinical trials. PROLASTIN-C is not indicated
as therapy for lung disease in patients in whom severe alpha1-PI deficiency
has not been established.
PROLASTIN-C may contain trace amounts of IgA. Patients with known
antibodies to IgA, which can be present in patients with selective or
severe IgA deficiency, have a greater risk of developing potentially severe
hypersensitivity and anaphylactic reactions. PROLASTIN-C is contraindicated
in patients with antibodies against IgA.
The most common drug related adverse reactions during clinical trials
in ≥1% of subjects were chills, malaise, headache, rash, hot flush, and
pruritus. The most serious adverse reaction observed during clinical studies
with PROLASTIN-C was an abdominal and extremity rash in one subject.
PROLASTIN-C is made from human plasma. Products made from human
plasma may carry a risk of transmitting infectious agents, eg, viruses and,
theoretically, the Creutzfeldt-Jakob disease (CJD) agent.
You are encouraged to report negative side effects of prescription drugs
to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088.
Please see brief summary of PROLASTIN-C full Prescribing Information
on adjacent page.
References: 1. Data on file, Grifols. 2. Campos MA, Alazemi S, Zhang G, Wanner A,
Sandhaus RA. Effects of a disease management program in individuals
with alpha-1 antitrypsin deficiency. COPD. 2009;6:31-40.
© 2013 Grifols Inc. All rights reserved. February 2013 PR33-0313
www.grifols.com