Our JourneyTo a Cure

7/29/2019 Our JourneyTo a Cure

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From Research to Results:


2/24ii ArthritisFoundationResearchReport

OurMission


3/24 FromResearchtoResults:OurJourneytoaCureforArthritis iii

The mission o the Arthritis Foundation

is to improve lives through leadership in

the prevention, control and cure o

arthritis and related diseases.


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5/24 FromResearchtoResults:OurJourneytoaCureforArthritis v

Letter fromOurPresident/CEOandVicePresidento f Research 1

ArthritisFailstoSidelineaYoungBaseballPlayer 2

Innovative Research Spotlight:EdwardMBehrens,MD 5

CloserthanEvertoAchievingaCure 6

Innovative Research Spotlight:GarryGold,MD 8

RaisingOurVoicestoFuelArthritisResearch 10

ConqueringArthritisTogether 12

Innovative Research Spotlight:LaurieHGlimcher,MD 14

Glossaryof Terms 15

TableofContents


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7/24 FromResearchtoResults:OurJourneytoaCureforArthritis 1

LetterfromDrKlippelandDrHardin

TheArthritisFoundationisdeeplycommittedtomovingarthritisresearchaheadandnding

treatmentoptionsthatmovebeyondwhatispossibletodayWithourhelp,thediscoveriesof

talentedandmotivatedscientistsmoveintotherealmof real-worldmedicine,changingthelives

ofpatientswitharthritisAsanorganization,wearecommittedtoeliminatingarthritisasthe

leadingsourceofdisabilityinthiscountry

Asthenationslargestprivatefunderof arthritisresearch,theArthritisFoundationprovides

innovativegrantsthatempoweryoungscientiststostudyenterprisingnewideasthatcouldleadto

themiracledrugsof thefutureThirteen-year-oldWillTellezisanexampleofthislife-changing

cycleinactionOnpage2,heshareshowdiscoveriesmadebyDrWilliamArend,anArthritis

Foundation-fundedyounginvestigator,ledtothedrugKineret,whichhasallowedWilltoovercome

theseverepainofjuvenilearthritisandthriveasanall-starbaseballplayer

Ourgrantprogramhasbroadreach,drawingproposalsfromthemosttalentedscientistsacross

thecountryAvigorouspeerreviewprocesswithtop,well-establishedmedicalexpertsensures

thattheproposalsweacceptareof thehighestqualityOnpage9,learnmoreabouttheArthritis

Foundationresearchprogram,theexcitingdiscoveriesthatmaybejustaroundthecorner,andthe

researchtrendswearewatchingclosely

Overtheyears,theArthritisFoundationhasbeenproudtoplayacriticalroleinkeepingthe

pipelineofyoung,motivatedscientistsopenbyprovidinggrantsatearly,criticaljuncturesin

theircareersSince1948,wehavefundedmorethan$400millioninresearchgrantsandmoving

forwardwewillcontinuetomobilizepublicandprivatefundingforresearchthatguidesand

acceleratesprogresstowardthepreventionandcureofosteoarthritis,rheumatoidarthritisand

juvenilearthritisRepresentingthe50millionAmericanssufferingfromarthritis,weaimtobring

togetherresearchers,clinicians,policymakers,patientgroupsandindustrypartnersaround

sharedresearchgoalsandstrategiesthatwillresultinmajorbenetsforpeoplewitharthritis

Welookforwardtoyourparticipationinthiseffortandtosharingtheresultsandimpactwithyou

infutureresearchreports

John H. Klippel, MD

President and Chie Executive Ofcer

Arthritis Foundation

John Hardin, MD

Vice President, Research


The Arthritis Foundation is committed to eliminating

arthritis as the leading source o disability in this country.


8/242 ArthritisFoundationResearchReport

FromInnovativeResearchtoRealWorldResults

1956

Research suggests

that RA is an

autoimmune

disease.

1949

The Arthritis and Rheumatism

Foundation unds its frst

research grant.

1948

Seven million Americans live

with arthritis. The Arthritis

and Rheumatism Foundation

is established.

Arthritis Nearly Strikes Out a Young Baseball Player

At 11 years old, Will Tellez was like many boys his age. A good student, he had many friends, loved

sports and especially loved baseball. That year, however, the Tellez family came down with a viral

infection. Everyone recovered except Will. His parents were worried. His doctors were bafed

and ordered testing in the hospital. At rst, nobody knew what it was, explains Wills mother,

Jeri Tellez. But six weeks later, they conrmed that he actually had juvenile arthritis. After that

initial diagnosis, Wills symptoms appeared to stabilize well enough for him to go home. Then, one

day later, he was back at the hospital with chest pains, which landed him in the ICU for three days.

Thanks in part to research funded 25 years ago by the Arthritis Foundation, 13-year-old Will Tellez is back playing the sport he loves.



1964

Arthritis and Rheumatism Foundation

becomes the Arthritis Foundation.1961

Dr. John Charnley

pioneers total hip

replacement.

1961

A clinical trial demonstrates the eectiveness o gold

therapy in treating rheumatoid arthritis.

He had fuid on his heart, recalls Jeri. It was unbelievably

rightening.

Will began seeing a pediatric rheumatologist, who diagnosed

that Wills orm o the disease was actually systemic onset juvenile

idiopathic arthritis, a orm o the disease that causes infammation

in the lining o the heart and lungs. The doctor prescribed

Kineret, a drug shown to be extremely eective in certain orms o

juvenile arthritis like Wills.

It elt like a miracle, says Jeri. The drug cleared up Wills

problems within just a ew days practically overnight.

An Overnight Success 25 Years in the Making

Wills dramatic recovery was actually the result o research

breakthroughs rst enabled by unding rom the ArthritisFoundation more than 25 years ago. It began in the early 1980s,

when Dr. William Arend, a young rheumatologist and researcher,

was studying how infammatory diseases developed. At the time,

he realized that rheumatologic joint infammation was caused, at

least in part, by an excess o cytokines. Cytokines are molecules

that ght inection in normal quantities, but cause infammation

and release tissue-destroying enzymes when present in excess. He

also realized that one cytokine in particular, called interleukin-1

(IL-1), was overly abundant in the tissue surrounding the joints o

rheumatoid arthritis patients.

Supported by the Arthritis Foundation, Dr. Arend began to

explore what was stimulating cells to produce too much IL-1 bytrying to encourage cells in the lab to generate the cytokine. In

doing so, he discovered a protein that blocked IL-1 reception.

The discovery o a mechanism that could be used to turn o

infammation in the body enabled researchers around the globe

to better understand the infammatory process.

The protein discovered by Dr. Arend went into clinical trials

in the 1990s, and in 2001 the biotech company Amgen developed

a recombinant, or cloned, version that would be marketed as

Kineret. Dr. Arend remembers that initial studies o the drug

actually proved to be disappointing because it didnt work as well

against rheumatoid arthritis as other products on the market.

But, he adds, against autoinfammatory disease in children,

the response was dramatic.Will Tellez is proo o that dramatic response. Without this

drug, Will might not be alive, says his mother. This orm o

arthritis builds up fuid on his heart and it can be lie-threatening.

Today, with Kineret, Will is an active 13-year-old all-star baseball

player who plays second base and center eld a position that

involves a lot o running. He gets a little sti rom time to time,

but he can run and play with the best o them, Jeri Tellez smiles.

The discovery by Dr William Arend of a protein that blocks the production

of interleukin-1 was instrumental in the development of Kineret, a drug

shown to treat autoinflammatory disease in children.

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FromInnovativeResearchtoRealWorldResults

1974

Congress passes the

National Arthritis Act.

1968

Dr. David MacIntosh

pioneers knee

replacement surgery.

Todays Research is Tomorrows Cure Arthritis Foundation Support Changes Lives

Will Tellez wasnt even born when Dr. Arend made the

discoveries that led to his successul treatment. But he and his amily

know the value o that early research. Arthritis changed my lie in a

bad way, says Will. Dr. Arend changed my lie a second time.

Dr. Arend nds it deeply satisying to see the results o his

research. It is the dream o every clinical investigator to work

on something that will lead to a treatment that helps patients,

he says. I am one o the ew to have seen that dream realized,

and in ways that no one ever anticipated. And that is a unique

experience. He asserts that Arthritis Foundation support was

essential to his work and remains critically important to the

innovative research that has ollowed. The Arthritis Foundation

provides grants and seed unding when ideas arent complete

enough or more long-term unding, says Dr. Arend. They

make it possible or people to ollow new ideas.

Arthritis Foundation Vice President or Research John Hardin

says: Bill Arends research that started more than 25 years ago is

saving lives and enabling children with arthritis to live, play and

grow up like other children. That uels my condence that todays

research will enable tomorrows cures.

The Arthritis Foundation

provides grants and seed undingwhen ideas arent complete enough

or more long-term unding.

They make it possible or

people to ollow new ideas.

William Arend, MD

1968

An Arthritis Foundation-unded

research study identifes Lyme

disease as a new disease.


11/24

1948

Seven million Americans live with arthritis.

The Arthritis and Rheumatism Foundation is

established.

1948


The Arthritis and Rheumatism Foundation is established.

1948


The Arthritis and Rheumatism Foundation is established.

FromResearchtoResults:OurJourneytoaCureforArthritis 5

Edward M. Behrens, MDAssistant Professor of Pediatrics, University of Pennsylvania

Attending Physician, The Childrens Hospital of Philadelphia

Arthritis Foundation Innovative Research Grant, 2010

On Track to Stop a Potentially Deadly Complication

InnovativeResearchSpotlight

Dr. Ed Behrens isnt easily satised with the way things are. Im always tryingto nd new and better ways of doing things, he says. He loves model railroadsbecause every design is a problem to solve.

He loves his work in pediatric rheumatology and rheumatologic researchfor similar reasons. A lot of amazing advances have happened in

the past 15 to 20 years with respect to autoimmune diseases, heexplains. But there are so many things we dont know yet; There areso many ways we can improve. Dr. Behrens believes that one keyarea for improvement is understanding how chronic inammationleads to Macrophage Activation Syndrome (MAS), a deadly complicationof many rheumatic diseases found most commonly in children.

MAS is particularly frightening and dangerous because it happens so quickly. In a matterof hours, one can go from being awake and alert to losing sensation, losing consciousness andslipping into a coma. Multiple organs of the body shut down and it can be easy to misdiagnose.MAS strikes about 10 percent of children with juvenile idiopathic arthritis.

Dr. Behrens is providing a better understanding of what causes MAS. Thanks to an InnovativeResearch Grant from the Arthritis Foundation, he is exploring new implications for treatment.

Dr. Behrens says: I cant stress how critical the Arthritis Foundation is for research. Inthis eld, there are never enough resources. When I rst started looking at MAS, nobody elsewas doing what I was doing. Without the Arthritis Foundation, my work wouldnt be possible.

Every day I go to work, Im getting a step closer to new answers, Dr. Behrens notes.As a physician, I see what inammation from arthritis can do to children and theirfamilies. I want to help them as much as possible. I get to take that determination to thelab, where I can work with novel therapies that can translate back to the clinic.

In many ways, the process of learning what causes and impacts MAS isnt all that different from the workDr. Behrens does at home with model trains. Even though the right combination of elements keeps the trains

running smoothly, the slightest shift can cause a complete crash. He believes that, unlike a model train set,his work with MAS is a continual problem-solving process that doesnt lead to answers overnight. But you donthave to spend a lot of time with children who have arthritis to see that its a problem well worth solving.

I cant stress how critical the Arthritis Foundation is orresearch. Without them, this progress wouldnt be possible.

Edward M. Behrens, MD



CloserThanEvertoAchievingaCure

1998

The FDA approves the frst TNF

inhibitor, Enbrel, or the treatment

o rheumatoid arthritis.

1988

The FDA approves methotrexate or treatment

o rheumatoid arthritis.

1983

Dr. William Arend, supported by an Arthritis

Foundation research grant, begins studying

how inammatory diseases developed and

discovers a protein that blocks IL-1 reception.

Dr. John Hardins career with the Arthritis

Foundation has deep roots. He received Foun-

dation fellowships in the 1970s and 1980s to

advance his understanding of the causes and

possible treatments of the disease. Today, he

is giving back to our cause by directing the

Foundations efforts to make even more prog-

ress in our persistent quest to prevent, control

and ultimately cure arthritis.

How has arthritis research changed over the course oyour career?

When I rst started out, doctors were treating arthritis patients

with gold injections and lots o aspirin. The results were about

what would have happened with no treatment at all: On average,

o every three patients, one would spontaneously get better, one

would continue to have the disease, and the third would have

aggressive disease that would eventually leave them crippled.

In the 1980s, we had a breakthrough with a drug called

methotrexate, which was being used in cancer treatment. Today,

it helps a large portion o patients get 50 to 75 percent better.

But methotrexate doesnt work or everyone, and it can weaken

resistance to inection overall.

Closer than Ever to

Achieving a CureJohn Hardin, MD, Refects on

Arthritis Research Through the Years

The Arthritis Foundation

encourages scientists to think in

new, big ways, and to try unproven

strategies. That is where break-

throughs begin. John Hardin, MD



2000

The Arthritis Foundation joins with the

Robert Wood Johnson Foundation to orm the

Alliance or Lupus Research.

1998

The North American Rheumatoid Arthritis Consortium

(NARAC) is established by the Arthritis Foundation,

the National Institute o Allergy and Inectious

Diseases, and the National Institute o Arthritis and

Musculoskeletal and Skin Diseases.

In 2000, we had another breakthrough with biologics:

medications produced by living cells in an incubator. They bind

to a specic molecule present in infammation and inhibit it.In rheumatoid arthritis (RA), we know the immune system is

activated in and around the joints, and that substances called

cytokines are important in this process. The rst set o biologics

targeted a cytokine called TNF-alpha, which is very important

in tissue injury. Newer biologics are now being developed as well.

Biologics are absolutely lie changing or many people. But most

still have some fares o the disease, and they need continued use

o these drugs to control that. It isnt a cure, and a percentage o

patients dont experience an acceptable level o remission.

Where do you envision the next research breakthroughs

occurring?

There is signicant potential or breakthroughs in so many

areas, especially in RA. I believe that the earlier people with RA

are treated, the more eective the treatment will be. We need to

identiy biomarkers that can determine what kind o drug is most

likely to be successul on a given patient. In other words, more

personalized medicine. To achieve that, we need to create patient

registries so we can analyze and correlate biological and treatment

inormation or large numbers o people with this disease.

The Arthritis Foundation is helping und data coordination

or TETRAD (Treatment Ecacy and Toxicity in Rheumatoid

Arthritis Database), which was launched by the National Instituteso Health (NIH) in 2009. Our goal is to correlate genetic data o

a large number o people with RA over the next two years. We

are also working on an alternative approach to developing a very

large registry or patients with RA. We reer to this new initiative

as AIR (Arthritis Internet Registry), which was initiated by the

Arthritis Foundation in 2010 and capitalizes on our relationship

with the million-plus people who have RA. Housed on our

website, an online questionnaire quickly conrms eligibility.

Then a lab contacts participants to acquire blood samples and

processes the data. This approach builds a real

partnership o scientists and patients in seeking

better ways to halt RA.

What about breakthroughs inosteoarthritis and juvenile arthritis?

The Centers or Disease Control and

Prevention (CDC) estimates that 27 million

Americans have osteoarthritis (OA) today,

and that number is growing as our population

ages. We also have an obesity epidemic,

resulting in OA at early ages. There are also

more athletic injuries especially anterior cruciate ligament

(ACL) injuries in girls and women, and a majority go on to

experience lie-altering arthritis in that joint. Presently we

do not have an eective intervention or OA other than joint

replacement surgery.

What is needed to move this eld orward is a way to detect

OA at a very early stage, even beore any symptoms appear. In other

words, we need a test that is the equivalent o a blood cholesterol

measurement as a predictor o cardiovascular disease or an imaging

strategy comparable to a bone scan or detecting osteoporosis.

For this reason, we are working to identiy biomarkers or OA.

Our strategy is to urther study a group o candidate measures

to determine i any o them correlate with and predict clinical

outcomes in patients with OA who have been ollowed over asignicant period o time. The NIH has already collected the

required material on a number o OA patients, and the Arthritis

Foundation is promoting an analysis o this material to determine

i any o the potential OA biomarkers has clinical utility.

Once we have a biomarker or OA, moving orward will be

much easier. Pharmaceutical companies already have products

on their shelves that could change the outcome or OA. These

products have not yet been tested, because without a biomarker,

relevant clinical trials could take many years to complete.

Continuedonpage9




Calling Dr. Garry Gold focused and motivated might be an understatement. He doesntdo anything halfway. After he tore his anterior cruciate ligament (ACL) during apickup basketball game, he took up running. Ten years later, he ran the rstof 20 marathons.

As a Silicon Valley electrical engineer, he wanted to make a biggercontribution to people. He didnt just go back to Stanford University fora masters degree in engineering and an opportunity to pursue MagneticResonance Imaging (MRI) research; he also went to Stanford School ofMedicine to become a doctor.

I was fascinated by MRI technology, says Dr. Gold. At the sametime, I felt that to make a true contribution in this area, Id bebetter off combining my love of research with a career in medicine.

His interest in arthritis grew from his own experiences with thedisease. I have osteoarthritis as a result of my own ACL injury, he says.

I also have students who have sustained joint injuries. We know they canreturn to sports, but we also know that they are at very high risk for arthritis in 10 to 15years. I want to do something to change that. I want to be contributing to health.

Today, Dr. Gold is focusing on early treatment for osteoarthritis, using an InnovativeResearch Grant from the Arthritis Foundation to develop new imaging methods todetect the earliest changes of OA in cartilage and other joint tissues. The sodiumMRI methodology weve developed in my lab makes it practical to see early changesin people who have injured their knees, he explains. When we see those earliestsigns of osteoarthritis, were hoping we can intervene, and demonstrate how earlyintervention can help.

Indeed, Dr. Gold isnt one to adopt a wait and see attitude toward anything. He mayhave had to stop running, but now hes training for a 100-mile bike ride. I refuseto be a pessimist, he smiles. Thats why I want us to nd tests that enable thedevelopment of new therapies, rather than wait for the therapies to come rst. I willneed a knee replacement in the next ve to 10 years, but Im determined not to seehistory repeat itself for todays young athletes.

Garry Gold, MDAssociate Professor, Department of Radiology and

Department of Orthopedics and Bioengineering, Stanford University


Reusal to Wait and See Drives New Thinkingor Early Detection

I know rsthand about injuries that can lead to arthritis.I want to do something to change things. Garry Gold, MD



In addition to promoting development o a biomarker or

OA, we are working with the Food and Drug Administration

(FDA) to nd ways to address new clinical trial designs that willdramatically speed up the drug discovery process.

Besides supporting researchers investigating arthritis in

children, were working closely with the Childhood Arthritis &

Rheumatology Research Alliance (CARRA), a national network

o pediatric rheumatology centers, which the Arthritis Foundation

helped ound. Our investment in the accelerated juvenile arthritis

research that CARRA makes possible will enable us to identiy

the best ways o matching patients with the right treatments at

the right time.

What will be necessary to take us to the next level?

There is no question that the level and pace o arthritis

research and unding must accelerate. We are talking about

a disease that is a principle driver o health care costs in this

country. There is no way to predict exactly how and when any

breakthrough will take place, but we are working on some concrete

initiatives, such as TETRAD and AIR, and we know how

much investment they will require. None o the breakthroughs

that we are looking or are going to happen without signicant

unding. And, o course, we need more than unding alone.

It is also critically important to encourage patients to

participate in clinical trials. Pharmaceutical companies und

some patient research, but not enough. NIH grants usuallyonly cover research that is already established. That is why

the Arthritis Foundation unds Innovative Research Grants,

which enable researchers to pursue and prove new approaches

and ideas, which we need to do at a greater depth.New breakthroughs also depend on improvements in patient

education and advocacy to get arthritis drugs into the marketplace

and ensure their saety. The Arthritis Foundation is theorganization

that represents the interests o patients with arthritis. We must

bring the disease into the public consciousness like never beore.

There is a huge deciency in pediatric rheumatology,

and we need more people to pursue it as a career. Our

advocacy plan is ocused on legislation to improve unding

or arthritis, which will bring more people into the eld

and encourage the development o arthritis specialists.

The power o basic science today, compared to when I rst

began, is amazing. Who could have imagined how ar we would

come? When I started working in this eld, we could hardly

imagine how to isolate proteins in the body. Now we can produce

them in a test tube. The scientic capability or a cure to arthritis

is in our hands. Think about HIV that causes AIDS. It was an

overwhelming disease that killed almost everyone who got the virus.

But there was a great push or advances in treatment, and now it

is so much more controlled. We need the same push in arthritis.

Why is supporting the Arthritis Foundation so important?

The Arthritis Foundation is involved not only in innovative

research, advocacy and education, but also in pulling theseelements together to take scientic discoveries through the

process o research, unding and development,

and to make them commercially available. The

scientic community in the United States is

very strong, with outstanding medical schools

and research institutions that prepare people

to embark on careers that can really make a

dierence. Unortunately, 90 percent o potentially

important research ideas go ununded because

they are based on unproven strategies.

The Arthritis Foundations Innovative Research

Grants encourage scientists to think in new, bigways, and to try unproven strategies. We believe

that is where breakthroughs begin. But right now

we need even greater unding to take us to the next

level, which will trigger even more government

support. We are motivated to make that happen.

CloserThanEvertoAchievingaCureContinuedfrompage7

Dr. John Hardin discusses the future of arthritis research with colleagues at the

Segal North American Osteoarthritis Workshop in Chicago.



Raising Our Voices to Fuel

Arthritis ResearchA cornerstone of the Arthritis Foundations

advocacy efforts is asking Congress to invest

more in arthritis research. We advocate for

continued investment in the National Institute

of Arthritis and Musculoskeletal and Skin

Diseases (NIAMS) to enable research into

better treatments and the search for arthritis

cures. Of the $550 million NIAMS budget, $246million was allocated for arthritis research in

2009 and $252 million in 2010.

The Arthritis Foundation has played an instrumental role

in supporting the American Reinvestment and Recovery Act

(ARRA), which augmented the amount o money the National

Institutes o Health (NIH) could invest in research by an

additional $10 billion. This meant an additional $6 million was

directed toward arthritis research in 2009, and another

$35 million in 2010.

The Arthritis Foundation also advocates or the

congressionally directed research program at the Department o

Deense (DOD). Because o the high incidence o osteoarthritis

among military veterans, the DOD has allocated approximately

$3.5 million or osteoarthritis research.

Advocacy is critical to unding research, says Arthritis

Foundation Vice President or Advocacy Amy Melnick. There

are so many dierent health issues competing or the same dollars.

Our voice must be heard. That voice is expressed through a

combination o concentrated education and communications in

Washington, D.C., combined with local eorts in the home states

o each member o Congress.

Besides advocating or research unding, Melnick adds

that the Arthritis Foundations eorts are also important to

drive research policy. We are the only nonprot organization

specically dedicated to arthritis research, advocacy and education

support. So we are able to convene the best and the brightest

rom every organization to determine and pursue the best

directions or research.

The statistics make the message abundantly clear, Melnick

points out. Fity million people in this country have arthritis. By

the year 2030, ully one-ourth o the United States population

will have this disease. And arthritis remains the number one cause

o disability in America. This is a critical public health issue and given the impact that disability has on businesses, it is an

economic issue as well. We cannot aord or it not to be a priority

and we must continually strengthen our voice. As more people

join our advocacy eorts, the stronger our voice will be. And the

stronger our voice is, the more likely the realities o arthritis are to

be heard, understood and acted upon.

CriticalRelationshipBetweenAdvocacy&Research



2001

Kineret, based in part on the protein

discovered by Dr. William Arend,

enters into clinical trials.2001

The Arthritis Foundation unds the establishment o

the Childhood Arthritis and Rheumatology Research

Alliance (CARRA).

2001

The Arthritis Foundations total cumulative investment

in research exceeds $300 million.

Dr. John H. Klippel and a group of arthritis advocates discuss the importance of doing more for people with arthritis with Congresswoman

Rosa DeLauro, far right.

As more people join us, the stronger our

voice will be. And the more likely the

realities o arthritis will be heard,

understood and acted upon. Amy Melnick, VP, Advocacy,




2009

CARRA receives support

or patient network

and patient registry

development.

2009

TETRAD, which was initiated with the

leadership o the Arthritis Foundation,

receives initial unding rom the NIH.2006

The FDA approves the second

generation o biologic agents or the

treatment o rheumatoid arthritis.

The Arthritis Foundation knows that strategic partnerships are vital to conquering this debilitating

disease. Since our founding in 1948, the Foundation has funded more than $400 million in research

initiatives that have had far-reaching even lifesaving impact, like young Will Tellez and his

mother tell about on page 2. While that investment alone is signicant, we know it will take much

more to create a world free of arthritis pain. Thats why we work closely with other organizations

that share our vision and can help expand our reach. Some recent examples follow.

Conquering Arthritis Together

David E. Shuey, Chair of the Arthritis Foundation national board of directors, with a participant of the 2010 Juvenile Arthritis Conference. T

Arthritis Foundation, along with CARRA, addresses causes, treatments and ultimately a cure for arthritis.

LeveragingResearchwithStrategicPartnerships



2030

The CDC estimates that 67 million Americans

(or 25 percent o the adult population) will

live with arthritis.

2010

The Arthritis Internet Registry is ormed to

harness the power o the Internet to connect

people with arthritis to clinical investigators.

2010

Fity million (one in fve) Americans

live with arthritis.

In 2010, along with the National Data Bank or Rheumatic

Diseases (NDB), the Arthritis Foundation launched AIR the

Arthritis Internet Registry to acquire, analyze and correlatedata rom a large sampling o people over three years. This

revolutionary platorm, and the research it enables, will help

physicians determine the right treatment at the right time

or individual patients who suer rom rheumatoid arthritis

(RA). AIR is also supported by researchers at Brigham and

Womens Hospital and Harvard Medical School and by Quest

Diagnostics. For more inormation, visit www.arthritis.org/

arthritis-internet-registry.php.

The Foundation is partnering with the National Institute o

Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

on TETRAD: the Treatment Ecacy and Toxicity inRheumatoid Arthritis Database. At 10 centers nationwide,

we und eorts to capture a broad range o clinical and

genetic data with the goal o developing personalized

medicine or patients with RA.

Biomarkers that measure and describe structure and

molecular changes in joints and predict the outcome o OA

are needed to develop new interventions or this disease. The

Arthritis Foundation is collaborating with the oundation o

the National Institutes o Health (NIH) to achieve this goal.

The OA Biomarkers Global Initiative is part o our

partnership with the Osteoarthritis Research SocietyInternational (OARSI). A workshop held in 2009

enabled doctors and researchers to explore the application

o biomarkers to clinical trials, analytical methods,

commercialization o biomarkers and goals or the uture.

Having played a key role in its development, the Arthritis

Foundation remains committed to the Childhood Arthritis

and Rheumatology Research Alliance (CARRA) and will

provide unds or support o the inrastructure upon which

CARRA depends. This robust national network o pediatric

rheumatology centers ocuses on addressing causes, treatments

and ultimately a cure or juvenile arthritis. CARRAs

inrastructure makes it easier to conduct large, multi-centerstudies involving a large number o children while reducing the

time it takes to achieve valid research results.

In recent years the Foundation has organized and hosted the

Segal North American Osteoarthritis Workshop (SNOW).

This event brings together more than 120 researchers rom

across the globe to examine critical questions that must be

answered in order to develop better treatments or OA.

In 2009, the Arthritis Foundation and the Centers or

Disease Control and Prevention (CDC) collaborated in a

yearlong eort around the public health and socioeconomic

impact o osteoarthritis. Outcomes included an OA Summitin Washington, D.C., which convened numerous government

organizations, academic and research institutions, advocacy

groups and health experts, as well as a major ollow-up report

o recommendations to alter the trajectory o OA.

Thanks to the Arthritis Foundations advocacy push,

the U.S. Department o Deense (DOD) committed

$3.5 million in new research dollars or post-traumatic

osteoarthritis. The appropriation in 2010 marked the rst

time Congress has listed arthritis as a research topic area or

the Peer Reviewed Medical Research Program (PRMRP).

The DODs unding decision was based on emergingdata suggesting a link between combat service and higher

incidence rates o the disease.

The need or arthritis research that can lead to productive new

treatment options has never been greater. As an organization ree

o political constraints, and representing the interests o the 50

million people diagnosed with arthritis, the Arthritis Foundation

is uniquely positioned to orge powerul partnerships that can

and do make a tremendous dierence.



Ask Dr. Laurie Glimcher what she nds most engaging about scientic research and she will tellyou she sees research as something of a treasure hunt. In fact, she nds the metaphor so ttingthat she titled an academic paper about her labs search for the T-beta transcription factor,Trawling for Treasure.1

You have to be tolerant of uncertainty and risk and willing to go after the unresolvedquestions, she explains. You dont always know exactly what youre looking for and

you dont always nd it. But, when you do, those moments are extraordinary.Dr. Glimcher has experienced many such moments in her career. Indeed, her laboratoryat Harvard, where she heads the immunology program, is known for its many discoveries,ranging from the T-beta transcription factor, which regulates a variety of immune functions,to the adapter protein that controls adult bone mass. The discovery of the adapterprotein was particularly exciting for Dr. Glimcher because it gave her the opportunity tocollaborate with her father, Dr. Mel Glimcher, a genetic biologist and orthopedic surgeon.

Most recently, her lab has been exploring NSAT factors that appear to govern the processby which bone is broken down in the body. Typically, osteoarthritis develops very slowly,states Dr. Glimcher. That makes it difcult to study. But our methodology made thedisease occur very rapidly. That can allow us to interrogate what happens genetically

and biochemically in the joints as theyre exposed to this process, opening the door totherapeutic intervention possibilities that simply dont exist for osteoarthritis right now.

As much as Dr. Glimcher enjoys asking and answering the big questions ofscientic research, she considers mentoring her most important task. Over theyears, she has helped scores of immunology researchers become established.Researchers who have worked with Dr. Glimcher hold her in such high regardthat they chose to celebrate her birthday not with a party but with asymposium in which her scientic progeny presented their research.

Im so proud when I look at the people Ive trained who are doing well.Several of them have achieved funding by the Arthritis Foundation. She

adds: There is no shortage of important work that needs to be done,questions to be asked and treasure to be found. The more peoplewho pursue work in this eld, the more we can all accomplish.

1Glimcher, Laurie H., Trawling or Treasure: Tales o T-bet, Nature Immunology 8, 448 - 450 (2007)


You dont always know exactly what youre looking or and you dont always nd it. But then, when you do, those

moments are extraordinary. Laurie H. Glimcher, MD

Laurie H. Glimcher, MDIrene Heinz Given Professor of Immunology, Professor of Medicine, Harvard Medical School

Senior Rheumatologist, Brigham and Womens Hospital


Uncovering Scientifc Treasure to Enrich Future Arthritis Research


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AIR (Arthritis Internet Registry)

An online national registry or patients with rheumatoid arthritisclosely related to the TETRAD registry. Patients can access AIRindependently o their physician.

Biologics

A term oten used to reer to medicines that are made in livingcells by incubators.

Biomarkers

A measure o a disease that helps establish the presence o thedisease or that provides prognostic inormation permitting aprediction o what will happen to the patient i the disease isnot treated. Typically carried out on blood or urine, but in some

cases a biomarker is a radiology procedure or a genetic test.An example is a bone density scan, which is a biomarker orosteoporosis that can predict risk o bone racture.

Cytokines

Small proteins secreted by cells o the immune system that areused to communicate with other cells.

Interleukin-1 (IL-1)

An important cytokine that is secreted by macrophages and is ableto induce vascular permeability, initiate ever, trigger chondrocytesto break down cartilage, and activate lymphocytes.

Macrophages

Large cells that ingest bacteria and other pathogens. Their job isto break down these pathogens and prepare molecules rom thepathogen as antigens that trigger immune responses by B and

T lymphocytes. Macrophages also secrete a range o cytokinesthat regulate the immune system; among them is TNF alpha, acytokine that activates many types o cells and is important inpromoting autoimmune diseases such as rheumatoid arthritis.

Macrophage Activation Syndrome (MAS)

A lie-threatening disorder associated with several orms ojuvenile arthritis, most commonly systemic onset juvenileidiopathic arthritis (SoJIA), or Stills disease.

T-beta Transcription FactorA protein that regulates specic genes within T lymphocytes.

TETRAD (Treatment Efcacy and Toxicity in Rheumatoid

Arthritis Database)

A national registry or patients with rheumatoid arthritis. Thisregistry was initiated through eorts o the Arthritis Foundation.Patients are registered in their doctors oce.

TNF Inhibitor

A molecule that blocks the biological action o TNF (tumornecrosis actor), a cytokine that is important in drivinginfammation such as that associated with rheumatoid arthritis.

Glossary

Research is crucialto nding solutions or

arthritis. Thats why its one

o our top prioritites.

John H. Klippel, MD

President & CEO, Arthritis Foundation

FromResearchtoResults:OurJourneytoaCureforArthritis 15



OurVision

The Arthritis Foundations vision is

to create a world ree o arthritis pain.


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