2014
Highlights
- Cultivating Collaborations that Thrive.
- Creating Impact Beyond the Laboratory.
- Bringing Bold Thinking to New Models.
A NEW VISION FOR DISCOVERY. Today’s health challenges are too complex to be solved by any single organization—government, business, academia or not-for-profit—working in isolation. But often these organizations are not experienced at identifying partners and forging productive relationships. At the FNIH, we are connected to key players in all of these sectors, and we can facilitate their collaboration because we have created management and funding models that make large-scale, multi-partner projects succeed. This is our vision for discovery—and it works.
Cultivating Collaborations that Thrive
Joining forces to accelerate drug development
New medicines that show promise in the laboratory often do not succeed in human testing. In fact, about 95 percent fail, typically late in the clinical trials process after millions of dollars have been invested. Such a high-cost, low-reward pipeline points to the need for a better understanding of how diseases develop at the molecular level—which is why the FNIH is helping to lead an unprecedented partnership to fill this need. Launched in 2014, the Accelerating Medicines Partnership (AMP) is a $230 million, five-year effort joining the forces of the FNIH, the NIH and the Food and Drug Administration (FDA) with those of not-for-profit organizations and 10 biopharmaceutical companies to devise a radically new approach to early-stage drug development. These companies have agreed to share expertise, resources and data to answer a critical question: Which biological pathways underlying a given disease are the best candidates for targeting new treatments? Instead of having different organizations pursue disparate pathways in isolation, AMP will generate pre-competitive, disease-specific data on the genetic and biological markers most likely to yield success when used as targets for new medicines. The data will be publicly available to the biomedical community so that many can use it as the foundation for drug discovery.
Accelerating Medicines Partnership (AMP)
Private Industry:
AbbVie
Biogen
Bristol-Myers Squibb Company
Eli Lilly and Company
GlaxoSmithKline
Janssen Research & Development, LLC
Merck Sharp & Dohme Corp.
Pfizer Inc
Sanofi
Takeda Pharmaceuticals
Not-for-Profit:
Alliance for Lupus Research
Alzheimer’s Association®
Alzheimer’s Drug Discovery Foundation
American Diabetes Association
Arthritis Foundation
Geoffrey Beene Foundation
Alzheimer’s Initiative
JDRF International
The Lupus Foundation of America
Lupus Research Institute
Pharmaceutical Research and Manufacturers of America
Rheumatology Research Foundation
USAgainstAlzheimer’s
AMP: Type 2 Diabetes
More than 100 million Americans already have type 2 diabetes or are at high risk, and 382 million people worldwide have a type 2 diagnosis. Although therapies are available, none can reverse the disease process or prevent the progression that leads to life-altering complications such as cardiovascular and kidney disease, limb loss and blindness. AMP partners will leverage the substantial amount of data already available from patients with type 2 diabetes and those at high risk to identify and validate DNA regions critical in the development or progression of the disease, with an eye toward identifying potential drug targets.
AMP: Alzheimer’s Disease
Alzheimer’s disease (AD) is the most common form of dementia, a condition that affects 36 million people globally—a number expected to skyrocket to 115 million by 2050 unless an effective therapy is developed. Scientists know that people with AD have the signature protein-based brain lesions called plaques and tangles; however, efforts to harness this knowledge to develop new therapies have not succeeded. AMP partners are working to establish an expanded set of biological markers that are present when AD develops, and then determine which are most promising for developing new treatments and predicting the likelihood of clinical response. The project will involve the large-scale analysis of brain tissue from AD patients and clinical trials to validate newly identified biomarkers.
AMP: Rheumatoid Arthritis & Lupus
Rheumatoid arthritis (RA) and lupus are just two of many disorders that occur when the immune system mistakenly attacks parts of the body that it is designed to protect, leading to inflammation that destroys tissues. Anti-inflammatory treatments can help, but most people with RA respond to current treatments only partially or temporarily. In the case of lupus, no effective targeted therapies exist for the most severe forms of the disease. AMP partners will analyze tissue and blood samples from people with RA and lupus to pinpoint genes, proteins, chemical pathways and networks involved at the cellular level. This is essential for developing targeted treatments for these debilitating conditions, but it also could shed light on the autoimmune process implicated in a wide range of diseases.
Creating Impact Beyond the Laboratory
The search for better tuberculosis treatments
Tuberculosis (TB) affected nine million people and caused 1.5 million deaths worldwide in 2013, affecting children and adults with HIV in developing nations particularly hard. TB is a bacterial infection that spreads through the air and attacks the respiratory system and other organs. Successful treatment requires taking multiple medications for several months, leading many patients to drop out prematurely—and remain contagious. Compounding this problem is the growing number of cases that are resistant to available drugs, most developed in the 1970s. With funding through the Bill & Melinda Gates Foundation, the Identification of high-quality HITs for Tuberculosis (HIT-TB) project at the FINH is helping to accelerate the search for new TB medications that could shorten and simplify treatment. This partnership includes the National Institute of Allergy and Infectious Diseases (NIAID), multiple pharmaceutical and agrichemical companies and several academic institutions to speed identification of compounds best suited for testing as potential drugs. The partners have shared their compound libraries and are using high-throughput screening to evaluate many molecules at once to identify “hits” to be prioritized for further study.
Genome exhibit reaches millions
Between June 2013 and August 2014, roughly three million Smithsonian visitors experienced Genome: Unlocking Life’s Code at the National Museum of Natural History, an exhibition made possible through funds raised, in part, by the FNIH. The result of a collaboration between the museum and the National Human Genome Research Institute, Genome awed visitors with the complexity and power of the human genome using 3-D models, interactive displays, custom animations and videos of real-life stories. It celebrated the 10th anniversary of the Human Genome Project and the successful sequencing of the human genetic blueprint, helping viewers understand how this knowledge is revolutionizing our understanding of human development, diversity and society, especially health and disease. In addition to the 4,400-square-foot exhibition itself, which took two years for museum designers and educators to develop and build, Genome included public events, educational symposia, an educators’ guide and the website www.unlockinglifescode.org. Genome is now on a multi-city tour that will take it to museums in California, the Midwest and Ontario through early 2018.
For an exhibition schedule, visit http://unlockinglifescode.org/traveling-exhibit
Support for a game-changing scientist
What if we could remove and replace damaged or defective parts of human DNA? Scientists have been working to find such a genome-editing tool, but Jennifer Doudna, Ph.D., Professor of Biochemistry, Biophysics and Structural Biology and a Howard Hughes Medical Institute Investigator at the University of California, Berkeley, stands apart. Dr. Doudna has focused her research on the structure of RNA, the molecule that carries out DNA instructions for creating the proteins that drive processes in the body. The FNIH awarded her the Lurie Prize in Biomedical Sciences in 2014 for that body of study, which includes her work on CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats), that are repetitive RNA sequences in bacteria that play a role in their immunity. Doudna discovered that pieces of CRISPR RNA team up with a protein called Cas9 to cut through the DNA of an invading virus. Doudna and her team then engineered their own RNA/protein combination and showed it can be used to precisely edit the DNA of plants, animals and humans. This CRISPR tool has to be managed with careful attention to bioethical concerns, but it could function as “molecular scissors” that can fix faulty genes underlying a range of diseases and health conditions.
Bringing Bold Thinking to New Models
Lung cancer: pioneering a more efficient approach to clinical trials
Patients with advanced squamous cell lung cancer have few good treatment options beyond surgery, yet the pace of traditional clinical trials remains slow, with most potential treatments never making it to the bedside. The Lung Cancer Master Protocol (Lung-MAP) trial, the result of a partnership that includes the FNIH, is pioneering a new model designed to speed access to investigational drugs for patients and allow multiple researchers to share one umbrella structure and recruitment process, significantly increasing their efficiency. Launched in June 2014, Lung-MAP uses genomic profiling technology to test patients for over 200 cancer-related genetic alterations, then assigns them to one of a number of investigational treatment studies based on their genetic profile. Within its first six months, Lung-MAP was enrolling patients at more than 400 sites in 39 states. The trial will add new investigational treatments over time, with the ultimate goal of testing 10 to 12 targeted therapies in 5,000 patients over the next five years. Besides the FNIH, partners in the effort include the National Cancer Institute, SWOG Cancer Research, Friends of Cancer Research, Foundation Medicine, five pharmaceutical companies and several lung cancer advocacy groups.
LUNG-MAP PARTNERS
American Lung Association
Amgen, Inc.
AstraZeneca Pharmaceuticals, LP
Genentech
MedImmune
Pfizer Inc
Lung-MAP Design Phase:
Amgen, Inc
AstraZeneca
Boehringer Ingelheim
Genentech
Janssen Research & Development, LLC
Eli Lilly and Company
Novartis Pharmaceuticals Corporation
Andrew & Lillian A. Posey Foundation
LUNGevity Foundation
Sarcopenia: defining diagnostic criteria for age-related muscle loss
Sarcopenia—age-related muscle loss and weakness—affects nearly 1 in 3 people over 60 and half of those over age 80. However, lack of an evidence-based definition for sarcopenia has limited our ability to understand its progression and develop strategies for prevention and treatment. This changed in April 2014 with the landmark publication of six special online articles in the Journals of Gerontology: Medical Sciences, which set forth data-driven diagnostic criteria for sarcopenia, including definitions of grip strength and muscle mass. The articles resulted from a collaborative project by the FNIH Biomarkers Consortium, the FDA, the National Institute on Aging and several pharmaceutical companies, in which researchers analyzed data from nine long-term epidemiologic studies involving over 26,000 healthy participants to generate a definition of sarcopenia. In addition to diagnostic criteria, the 2014 publications provide specific characterizations of how low lean mass and low strength relate to problems with mobility. This new information is expected to influence treatment decisions and help identify groups of at-risk patients who are good candidates for testing interventions.
[Biomarkers Consortium—Sarcopenia Partners]
BIOMARKERS CONSORTIUM—
SARCOPENIA PARTNERS
Abbott Nutrition
Amgen, Inc.
Dairy Research Institute
Eli Lilly and Company
Merck Sharp & Dohme Corp.
Novartis Pharmaceuticals Corporation
River blindness: moving beyond control to elimination
Over the past few decades, focused efforts to control the tropical disease onchocerciasis, or river blindness, have drastically lowered incidence in South and Central America, but the disease continues to have a devastating impact in sub-Saharan Africa. River blindness is caused by Onchocerca volvulus worms, which are transmitted to humans through repeated bites from infected blackflies. Mass administration of the drug ivermectin is an effective control strategy, but it does not guarantee elimination of the disease from a population, as people can carry the worms without exhibiting symptoms. The FNIH is working with the NIAID to determine if a blood or urine test could be developed to identify people who are carriers of adult female Onchocerca volvulus worms (OvAF). Once inside a human host, these females produce smaller larvae that over time can cause chronic skin disease, severe itching and eye lesions that lead to blindness. Knowing if someone is a carrier would ensure they could be treated and prevent transmission of the worms to uninfected blackflies. The FNIH and NIAID are studying OvAF and OvAF-infected humans to identify biomarkers in blood and urine that might indicate the presence of the female worm, and then test and validate the most promising candidates. The ultimate goal is a point-of-care test that would help eradicate river blindness around the globe.