Volume 9 / Issue 2 / March 2013

Maria Carrillo succeedsWilliam Thies

as vice president for medical and

scientific relations

Maria C. Carrillo, PhD, is the Alzheimer’s Association’s new

vice president for medical and scientific relations. Carrillo,

who joined the Association in 2005 as director of science

grants, succeeds William Thies, PhD, who had led the Asso-

ciation’s Department of Medical and Scientific Relations

since 1998.

An Association spokesperson on a wide range of medical

and scientific issues, Carrillo led the Alzheimer’s Association

International Research Grant Program (IRGP), the world’s

largest nonprofit funder of Alzheimer’s research, and con-

tinues to lead the Alzheimer’s Association Research Round-

table, a consortium of scientists from academia, industry, and

government agencies collaborating to overcome universal

barriers to progress in developing effective treatments for

Alzheimer’s disease (AD). Carrillo is among the internation-

ally recognized authors of the AD diagnostic guidelines and

criteria issued jointly in 2011 by the National Institute on

Aging and the Alzheimer’s Association.

Carrillo’s core areas of expertise include the emerging ef-

fort to identify biomarkers of AD and other dementias

through brain imaging, cerebrospinal fluid (CSF) protein

analysis and other research strategies. She coordinates the

Association’s leadership of the World Wide Alzheimer’s

Disease Neuroimaging Initiative (WW-ADNI), an interna-

tional effort to expand the North American ADNI to

include data generated by related studies around the globe;

Association involvement in the Biomarkers Consortium,

a private–public partnership to accelerate biomarker devel-

opment; and the Global Alzheimer’s Association Interactive

Network, which uses cloud computing to facilitate data

sharing among researchers and accelerate progress toward

improved treatments for AD.

In addition, Carrillo heads the Alzheimer’s Association

Quality Control Program for CSF Biomarkers and the

Neuroimaging Professional Interest Area of the Alzheimer’s

Association International Society to Advance Alzheimer’s

Research and Treatment (ISTAART).

Thies, known for his big-picture view of the opportu-

nities and challenges facing the AD science community,

sought to increase the opportunities and decrease the

challenges in myriad ways during his tenure at the Asso-

ciation. Understanding the value of collaboration on

both a large and small scale, he developed relationships

with agencies such as the National Institute on Aging

that are influential in advancing AD science, and he ex-

panded avenues for individual researchers to connect

and advance individual research projects. Thies was

instrumental in bringing the former International Confer-

ence on Alzheimer’ Disease under the umbrella of

Association science initiatives. Now the Alzheimer’s Asso-

ciation International Conference, the annual meeting of

AD and dementia researchers and clinicians is the world’s

largest conference of its kind.

Other components of the Association’s science program

that were added during Thies’ tenure include the Alz-

heimer’s Association Research Roundtable, which grew

from having four corporate sponsors in 2003 to having 26

today; an AD professional society, ISTAART; the

Alzheimer’s Association TrialMatch� clinical trials matching

service; and Alzheimer’s & Dementia: The Journal of the

Alzheimer’s Association.

The IRGP underwent notable growth under Thies’

stewardship, with the program’s budget doubling and grant

categories being added to ensure that researchers at all stages

of their careers, including new investigators, were eligible to

apply. Thies’ foresight regarding knowledge that was essen-

tial for developing disease-modifying AD treatments con-

tributed to the Association’s decision in 2006 to provide its

largest grant at that time, more than $2 million, to expand

ADNI to include imaging of participants using the radio-

tracer Pittsburgh compound B, which identifies the presence

of the AD protein amyloid-beta in the brain. That study and

many studies that followed confirmed the value of the radio-

tracer as a tool for identifying those at highest risk of AD

who might benefit most from a disease-modifying treatment

when a treatment became available. In 2011 and 2012, Thies

and other Association scientists teamed with the Associa-

tion’s Relationship Development Division to identify do-

nors who would understand the groundbreaking potential

of the Dominantly Inherited Alzheimer Network Trials

Unit (DIAN TU) to detect drugs that might stop or slow

the disease and who would step forward with financial sup-

port for DIAN TU. In 2012, their efforts culminated with

a $4.2 million grant from the Association to DIAN TU.

Clinical trials of three drugs are expected to begin in 2013.

Alzheimer’s Association president and Chief Executive

Officer Harry Johns remarked on Thies’ achievements,

saying “Bill has been not only a valued leader of all of the

Association’s science work, but he has also been a true leader

of the Alzheimer’s research community.”

Thies plans to return to the Association part-time as

senior scientist in residence.

Alzheimer’s Association / Alzheimer’s & Dementia 9 (2013) 246–249 247

Brain mapping project, Medicare

Advisory Committee decision, U.S.

Food and Drug Administration (FDA)

guidance on drug development

January and February brought several announcements from

the U.S. government that are of interest to AD scientists,

clinicians, and advocates.

Brain mapping project

In his February 12 State of the Union address, U.S. President

Barack Obama commented on the potential of research to

spur economic benefit, saying, “Every dollar we invested

to map the human genome returned $140 to our economy.

Today, our scientists are mapping the human brain to unlock

the answers to Alzheimer’s, developing drugs to regenerate

damaged organs.Now is not the time to gut these job-

creating investments in science and innovation. Now is the

time to reach a level of research and development not seen

since the height of the Space Race” [1].

A few days later, the Alzheimer’s Association learned of

the anticipated proposal of a decade-long, federally funded

project to map the activity of the human brain. According

to an article in The New York Times, the project may be pro-

posed publically as early as this month and is “seeking to do

for the brain what the Human Genome Project did for ge-

netics” [2, p. A1].

According to the article, “The [Brain ActivityMap] proj-

ect.will include federal agencies, private foundations and

teams of neuroscientists and nanoscientists in a concerted ef-

fort to advance the knowledge of the brain’s billions of neu-

rons and gain greater insights into perception, actions and,

ultimately, consciousness. Scientists with the highest hopes

for the project also see it as a way to develop the technology

essential to understanding diseases like Alzheimer’s and Par-

kinson’s, as well as to find new therapies for a variety of men-

tal illnesses” [2, p. A1].

Federal agencies may include the National Institutes of

Health, Defense Advanced Research Projects Agency,

and National Science Foundation, all coordinated on this

project by the White House Office of Science and Tech-

nology Policy.

Scientists stating that they were involved in the planning

of the project toldThe New York Times that they hope federal

financing for the project would be more than $300 million

a year, or $3 billion over 10 years, if the project is approved

by Congress.

According to The Times, the Human Genome Project

cost $3.8 billion. It was begun in 1990 and its goal, the map-

ping of all the genes in human DNA, was achieved in 2003.

A federal government study of the impact of the project

indicated that it returned $800 billion by 2010 [2].

The Alzheimer’s Association applauds a large-scale effort

to map brain activity, and recognizes that it is a vastly more

complicated undertaking than even the Human Genome

Project. At the same time, mapping the activity of the human

brain is a long-term project, and the nation must not lose

sight of the aggressive timeline set by the National Alz-

heimer’s Plan Advisory Council and Health and Human

Services Secretary Kathleen Sebelius to delay, effectively

treat, or prevent AD by 2025.

At its January 14, 2013, meeting in Washington, DC, the

Advisory Council voted unanimously to approve a new set

of recommendations. These recommendations will be sent

to Secretary Sebelius and Congress for review and inclusion

into the first update of the National Alzheimer’s Plan. One

of the important additions is the specification of research

milestones that must be accomplished to remain on track

to achieve the 2025 goal.

Medicare Advisory Committee decision on

amyloid imaging coverage

To provide guidance for physicians, individuals and families

affected by AD, and the public, the Society of Nuclear

Medicine and Molecular Imaging (SNMMI) and the Alz-

heimer’s Association jointly published the first criteria for

the appropriate use of positron emission tomography

with FDA-approved amyloid radiotracers to help diagnose

people with suspected AD. The criteria were published on-

line January 28, 2013, as an article “in press” by Alzheimer’s

& Dementia [3] and The Journal of Nuclear Medicine [4].

“Our primary goal is to provide health care practitioners

with the information and options available to provide

patients with the best possible diagnosis and care in a cost-

effective manner,” said Association Vice President for Med-

ical and Scientific Relations Maria Carrillo.

The Centers for Medicare & Medicaid Services (CMS),

the U.S. government agency that decides which medical

services are covered for Medicare and Medicaid partici-

pants, called a Medicare Evidence Development & Cover-

age Advisory Committee (MEDCAC) meeting January 30

to discuss the criteria.

The outcomes of special interest to CMS were patient

function and quality of life. CMS asked theMEDCAC panel

of 15 physicians and scientists for their input on these topics

as well as whether the published evidence identified patient

characteristics that would predict improved health outcomes

with the imaging test. After hearing from several experts in

the field, the panel concluded that current evidence was in-

sufficient to show improved function, quality of life, or

health outcomes.

The Association was disappointed with the decision and

urged the panel to reconsider the evidence. The Association

believes that early detection leads to improved clinical deci-

sion making, better outcomes, and higher quality of life for

people with AD and their families by enabling earlier access

to appropriate treatments; allowing the family to build a care

team and seek out education and support services; enabling

Alzheimer’s Association / Alzheimer’s & Dementia 9 (2013) 246–249248

enrollment in AD/dementia clinical trials; and providing an

opportunity for the development of advance directives and

financial planning. The SNMMI was similarly disappointed,

stating that current evidence “supports the ability of beta-

amyloid imaging to change patient management, leading

to better outcomes” [5].

CMS is expected to make a decision on coverage, based

on MEDCAC proceedings and other data, in summer 2013.

Guidance on drug development for early AD

Public comment is being accepted until April 9 on the FDA

Draft Guidance for Industry on Developing Drugs for Early-

Stage Alzheimer’s [6]. Comments may be posted online at

http://www.regulations.gov/#!documentDetail;D5FDA-

2013-D-0077-0001.

The guidance document from the U.S. FDA shares the

agency’s perspective on topics such as ways researchers can

identify and select patients with early-stage AD, or those

who are at risk of developing the disease, for participation

in clinical trials; how researchers can assess the outcome

of a drug intervention in people with early-stage AD;

and how trial sponsors can demonstrate disease modification

in AD.

Said Russell Katz, MD, Director of the Division of

Neurology Products in the FDA’s Center for Drug Eval-

uation and Research, “The scientific community and

the FDA believe that it is critical to identify and study

patients with very early Alzheimer’s disease before there

is too much irreversible injury to the brain. It is in this

population that most researchers believe that new drugs

have the best chance of providing meaningful benefit to

patients” [7].

Explained Katz, “This draft guidance is intended to serve

as a focus for continued discussions [among] the FDA and

pharmaceutical sponsors, the academic community, advo-

cacy groups, and the public. The FDA is committed to

vigorously addressing Alzheimer’s disease and will work

with industry to help develop new treatments in this early

population as expeditiously as possible” [7].

Expanding the AD research portfolio

Through its own grant programs and in collaboration with

other organizations, the Association is helping to expand

the AD research portfolio worldwide.

International Research Grant Program (IRGP)

The Alzheimer’s Association IRGP has awarded its first

grants through the recently established New Investigators

Program. A total of 106 applications were submitted; 26

research proposals were awarded funding in December

2012. Funding totaled more than $2.5 million.

About half the funded grants study the molecular mech-

anisms that contribute to disease-related processes, including

the production of amyloid-beta and the abnormal chemical

alterations of tau. Approximately 25% investigate brain im-

aging, biomarkers, and clinical tools that may result in earlier

and more accurate diagnoses. The remaining grants examine

novel treatment strategies for AD, nonpharmacological

interventions, ways to improve care for people with demen-

tia through new technologies, factors such as blood vessel

damage and genetic risk factors that may contribute to AD

and other dementias, and the values and beliefs of diverse

cultures that impact use of health care.

From March through June 2013, applications submitted

to the 2013 All Investigators Program (new, midcareer,

and senior investigators) will undergo peer review. Award

recipients will be announced in August, with the exception

of Zenith Award winners, who will be announced in No-

vember. New to the All Investigators Program this year is

a targeted request for applications called Understanding

the Development of and Devising Treatments for Alz-

heimer’s Disease in Individuals with Down Syndrome. Of-

fered in partnership with the Global Down Syndrome

Foundation and the Linda Crnic Institute for Down Syn-

drome, this grant category focuses on pilot research and

proof-of-principle studies for new and established investiga-

tors to understand more completely the mechanisms leading

to AD in individuals with Down syndrome.

Zenith Award winners for the 2012 All Investigators Pro-

gram received a total of $2.25 million in funding. They were

� Khalid Iqbal, PhD, Research Foundation for MentalHygiene, Inc., at New York State Institute for BasicResearch, Staten Island, New York, for the study“Shifting balance from neurodegeneration to regen-eration”

� Robert Siman, PhD, University of Pennsylvania,Philadelphia, for the study, “Functional assessmentand treatment of progressive tauopathy”

� Mark H. Tuszynski, MD, PhD, University of Califor-nia, San Diego, La Jolla, California, for the study,“MRI guidance for BDNF gene delivery in AD”

� Robert J. Vassar, PhD, Northwestern University, Chi-cago, Illinois, for the study, “Identifying novelBACE1 substrates and interacting proteins in thebrain”

� Lon White, MPH, MD, Pacific Health Researchand Education Institute, Honolulu, Hawaii, forthe study, “Honolulu–Asia Aging Study: clinical–neuropathologic analyses”

Since 1982, the IRGP has awarded more than $300 mil-

lion to 2100-plus research projects. For more information

on the IRGP, visit www.alz.org/grants.

Part the Cloud (PTC)

PTC grants were established in 2012. The aim of PTC grants

is to fill the gap in AD drug development by providing

Alzheimer’s Association / Alzheimer’s & Dementia 9 (2013) 246–249 249

support for early-phase studies of potential AD therapeutics

or validation of biological markers of disease progression.

Only applications from Northern California academic in-

vestigators and small for-profit entities with lead candidate

therapeutic agents that require early stage testing are

accepted. Three PTC grants totaling $1.4 million were

awarded in 2012. Recipients were

� Adam L. Boxer, MD, PhD, University of California,San Francisco, for the study, “Phase I multiple as-cending dose trial of the MT stabilizer TPI-287 forAD”

� Pharmatrophix, Inc., Menlo Park, California (leadscientist, Frank Longo, MD; Stanford University,Stanford, California), for the study, “Phase I trialfor P75 receptor ligand”

� ADNI (principal investigator, Michael Weiner, MD;University of California, San Francisco, and SanFrancisco VAMedical Center), for the study, “WholeGenome Sequencing Project–ADNI”

International Alzheimer’s Disease Research

Portfolio

The Alzheimer’s Association, National Institutes of Health,

and other organizations that provide AD research funding

have collaborated to provide information on funded pro-

jects in one central location, the International Alzheimer’s

Disease Research Portfolio (IADRP). The IADRP, devel-

oped by the National Institute on Aging, is a database of

funded AD research from around the world. The goals of

the IADRP are to

1. Enable funding organizations to assess the scope andscale of current AD research

2. Coordinate funding strategies among organizations3. Leverage research-related resources4. Avoid duplication of effort5. Identify gaps in research funding and promising new

areas of study

The IADRP features a publicly available database of AD

research studies, programs, and initiatives underway in the

United States and internationally. AD researchers can

search the database for research being conducted on

specific topics organizations funding AD research can use

the database to track patterns of AD research funding

over time and to compare research areas supported by dif-

ferent organizations.

To make such searches possible, the Alzheimer’s Associa-

tion and National Institutes of Health partnered to develop

a common system for classifying the wide range of

Alzheimer’s research conducted. Called the Common

Alzheimer’s Disease Research Ontology, or CADRO, the

system is organized around seven major categories: molecu-

lar pathogenesis and pathophysiology of AD; diagnosis,

assessment, and disease monitoring; translational research

and clinical interventions; epidemiology; care, support,

and health economics of AD; research resources; and

consortia and public–private partnerships.

For more information on the IADRP, to search the

IADRP database, or to find out how your organization can

become an IADRP member, visit http://iadrp.nia.nih.gov.

References

[1] State of the Union address. 2013 Feb 12.

[2] John Markoff. Obama seeking to boost study of human brain. The

New York Times; 2013 Feb 18. page A1.

[3] Johnson KA, Minoshima S, Bohnen NI, Donohoe KJ, Foster NL,

Herscovitch P, et al. Appropriate use criteria for amyloid PET: a report

of the Amyloid Imaging Task Force, the Society of Nuclear Medicine

and Molecular Imaging, and the Alzheimer’s Association. Alzheimer

Dement January 28, 2013. In Press.

[4] Johnson KA,Minoshima S, Bohnen NI, Donohoe KJ, Foster NL, Her-

scovitch P, et al. Appropriate use criteria for amyloid PET: a report of

the Amyloid Imaging Task Force, the Society of Nuclear Medicine

and Molecular Imaging, and the Alzheimer’s Association. J Nuclear

Med. Published online ahead of print, January 28, 2013.

[5] Society of Nuclear Medicine and Molecular Imaging Statement on

MEDCAC Meeting for Brain Amyloid Imaging. http://interactive.

snm.org/index.cfm?PageID=12342. Accessed March 6, 2013.

[6] Guidance for Industry, Alzheimer’s Disease: Developing Drugs

for the Treatment of Early Stage Disease. U.S. Department of

Health and Human Services, Food and Drug Administration, Cen-

ter for Drug Evaluation and Research. http://www.fda.gov/down

loads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/

UCM338287.pdf. Accessed March 6, 2013.

[7] FDA offers new guidance on developing drugs for Alzheimer’s

disease. U.S. Food and Drug Administration. http://www.fda.gov/

NewsEvents/Newsroom/PressAnnouncements/ucm338659.htm. Ac-

cessed March 6, 2013.