| ID | Title | Body | Facebook Description | Facebook image | Facebook Title | Facebook Video | Twitter Description | Twitter Image | Twitter Title | Meta tags |
|---|---|---|---|---|---|---|---|---|---|---|
| 584 | NIH and Eli Lilly Publish Guide to Help Researchers Develop Therapeutic Screening Tests | On May 2, NCATS and Eli Lilly and Company jointly released an online Assay Guidance Manual designed to provide researchers with step-by-step guidance through the complex process of turning a basic research finding into an assay that will start the process of discovering pharmacological tools and drugs. Assays are laboratory tests that enable researchers to examine thousands of compounds using state-of-the-art high-throughput screening systems critical to drug discovery. Results from assays, known as chemical probes, can help scientists study protein and cell function as well as biological processes relevant to physiology and disease. This knowledge enables scientists to optimize these probes as potential candidates in the drug development pipeline. The Assay Guidance Manual highlights best practices and features topics such as developing optimal assay reagents, protocols, data standards and performance validation tools. It also provides clear guidelines for scientists in academia, nonprofits, industry and government who want to develop potential assay formats compatible with high-throughput screening and structure activity relationship measurements of new and known molecular compounds. More than 100 authors from around the world contributed content to this free tool, which is housed by the National Library of Medicine (NLM). NCATS plans to continually update and expand the content with contributions by scientists working in various disciplines of translation, drug discovery and drug development. The manual previously existed as a wiki administered by what is now the NCATS Chemical Genomics Center (NCGC). The wiki had more than 53,000 unique visitors during the last year, with 56 percent of visits originating from 153 countries outside the United States. "We hope to reach a larger audience through the NLM site and form collaborations with researchers worldwide," said Sitta Sittampalam, Ph.D., senior scientist at NCATS and editor-in-chief of the Assay Guidance Manual. Sittampalam previously worked at Lilly and was a driving force in the initial collaboration with NCGC. "This has been an intense two-year endeavor; the commitment of my co-editors, authors and NLM collaborators to sharing this knowledge with the broader scientific community is an important legacy." Posted May 2012 | ||||||||
| 583 | New Drug for Rare Type of Cystic Fibrosis | Patients with a rare type of the deadly lung disorder cystic fibrosis may be able to breathe easier thanks to a new drug that targets the defective protein causing the disease. Researchers from 13 universities and hospitals, including 10 CTSA institutions, partnered with the Cystic Fibrosis Foundation and the drug manufacturer Vertex Pharmaceuticals to conduct clinical trials and obtain FDA approval for the drug Kalydeco as a new treatment. An estimated 30,000 people in the United States and 70,000 worldwide have cystic fibrosis, an inherited disease that causes thick, sticky mucus to clog the lungs and other organs, leading to life-threatening infections, digestive problems and usually death in early adulthood. People with cystic fibrosis have a mutation in a gene that produces cystic fibrosis transmembrane conductance regulator (CFTR), a protein that regulates the movement of ions and water in the body. Although medical advances have improved life expectancy, the impact of cystic fibrosis remains substantial. Kalydeco is an oral medicine that could greatly improve the lives of individuals living with a rare form of cystic fibrosis caused by a specific genetic mutation in the CFTR gene, G551D-CFTR, which occurs in approximately five percent of individuals with cystic fibrosis. It is the first treatment that targets the defective protein that causes cystic fibrosis, as previous treatments have targeted only the secondary effects of dysfunction. In clinical trials, researchers found that patients with this particular mutation showed improved lung function following treatment with Kalydeco. These patients also showed improvements in other critical areas, including decreased respiratory distress symptoms, weight gain, and signs that their bodies were better able to carry salt in and out of cells. The breadth of research and funding partners behind this study embodies the idea of team science, a cornerstone of the CTSA program. The research also highlights the potential of personalized medicine. Now, with this new understanding, physicians can tailor treatments to their patient’s genetic makeup. As more drugs are designed for specific genetic profiles, doctors will be able to match the best treatment with a given patient, ultimately enabling the right medicine to be delivered to the right patient at the right time. Posted March 2012 | ||||||||
| 582 | Converting Brain Signals into Action | Today, 8 million Americans are living with paralysis or have lost limbs. Many could benefit from technologies that would help them carry out daily activities, but high-tech prosthetics or other such devices are not always sufficient to meet these needs, particularly for those who are paralyzed. To improve the quality of life for these individuals, NCATS-supported investigators at Pitt are exploring two different computerized chips that convert brain signals into an action simply through the patient's thinking about the action. "The problem has always been the control of the prosthetic by someone with limited ability to move," said Michael Boninger, M.D., professor and chair of the Department of Physical Medicine and Rehabilitation at the Pitt School of Medicine. Boninger and Andrew Schwartz, Ph.D., a professor of neurobiology at the medical school, have built a collaborative research program to develop brain-computer interface devices that interpret the brain's still-intact command abilities and convey them to high-tech prosthetics and assistive devices. A team of NCATS-supported researchers at the University of Pittsburgh developed a micro-electrocorticography grid that may help paralyzed individuals move again. The device, which is implanted in the brain's movement-controlling motor cortex (see image inset), helps this study participant practice simple computer tasks using only her mind. A computer system interprets her brain's electrical impulses captured by the device then converts the signals into movement controls in virtual environments. (University of Pittsburgh School of Medicine Photo) "There is a really collaborative group of researchers at Pitt," said Boninger. "It's a critical mass supported by the Clinical and Translational Science Institute." The university's CTSI is one of about 60 research institutions supported by NCATS' Clinical and Translational Science Awards (CTSA) Program, which aims to move scientific innovations into clinical practice. Currently, the research team is working in parallel on two devices with unique features. One of these, the micro-electrocorticography (ECoG) electrode grid, is placed beneath the skull and on the surface of the brain's movement-controlling motor cortex. A computer system interprets the electrical impulses in the brain captured by the micro-ECoG technology and then converts the signals into movement controls in virtual environments. The group at Pitt developed the device as a smaller, less invasive and higher-resolution version of an ECoG grid that is used to monitor intractable epileptic seizures prior to surgery. "We wanted to accelerate the translation of this into clinical work, starting with what was available and approved for clinical use," recalled team member and biomedical engineer Wei Wang, M.D., Ph.D., who is an assistant professor in Boninger's department and a co-principal investigator of the CTSI-funded pilot research. "Our first phone call was to the CTSI," said Boninger. Before each phase of research into their micro-ECoG grid, the collaborators met with the regulatory experts at the CTSI for guidance on the requirements for human research. Wang added, "I think that without their help, it would have been a much tougher route to take, and may not have happened." In addition to specialized expertise, Boninger's research team received two grants from the CTSI to facilitate the project. First, a Translational Tool Pilot Project award to co-principal investigators Wang and Elizabeth Tyler-Kabara, M.D., Ph.D., assistant professor of neurosurgery and bioengineering at Pitt, made it possible for the team to map out the brain signals corresponding to specific hand movements. The team then worked with patients who were undergoing epilepsy monitoring for a week and were willing to have the experimental micro-ECoG grid implanted alongside their clinical ECoG grid. Using only their minds via the brain interface device, the volunteers practiced computer-screen tasks and a video game. Building upon this work, Wang received a training grant from the CTSI's Clinical Research Scholars Program. This grant enabled continued research funding and formal mentorship support from Boninger and Schwartz as well as educational opportunities in various aspects of clinical and translational research. Leveraging funding from NIH's National Institute for Neurological Disorders and Stroke, Schwartz and Pitt bioengineer Jennifer Collinger are working with Wang to test the micro-ECoG technology with people who have tetraplegia, or paralysis in all four limbs. In this study, volunteers will have more time to master use of the implanted brain interface device, spending 25 hours per week for nearly a month testing their control of computer cursors and assistive devices. The group also is developing a second brain-interface technology, an intracortical microarray. This device enables the user to control movement with thoughts, but with a higher resolution and potentially greater control than the micro-ECoG because the tiny chip's 100 miniscule, spike-like electrode probes descend into the surface of the motor cortex. The probes read the signals coming from individual neurons. Because the arrays are embedded into the brain, this interface device could cause more scar tissue than the micro-ECoG. With support from the Defense Advanced Research Projects Agency, Schwartz is leading research using the array in animals paired with a dexterous prosthetic arm engineered at Johns Hopkins University. With coaching from CTSI and other university experts, the team received approval from the U.S. Food and Drug Administration to test the intracortical array in humans. Now supported by the U.S. Department of Defense, Schwartz is continuing his animal model work, and Boninger is leading its testing in volunteers with tetraplegia. "Our work is a great example of translational research that accomplishes things that we're not going to get from a pill," Boninger said. "Support of bioengineering research is an absolutely critical part of the CTSI program." Posted March 2012 | ||||||||
| 581 | Lighting a Path for Improved Cancer Treatment | Sometimes researchers quickly connect the dots that help advance medicine. That seems to be the story of Cornell dots — or C-dots — the silica nanoparticles that are lighting a path toward improved cancer imaging and drug delivery. Where other methods have failed, these fluorescent C-dots (see box) have been shown in animals to safely light up cancer cells, track their movement and then quickly exit the body. Michelle Bradbury, M.D., Ph.D., a clinician-scientist at Memorial Sloan-Kettering Cancer Center (MSKCC) in New York City, will test multimodal C-dots in humans for the first time. She believes that imaging metastatic tumors with these tiny particles could one day help surgeons better define tumor borders, find diseased lymph nodes, and see where cancer has spread in patients' bodies for targeted tumor therapy — all in one platform and without negative side effects.Bradbury credits innovative funding and a diverse team of experts at both MSKCC and Cornell University with facilitating her research and expediting a usually lengthy research process. By joining forces with C-dot creator and Cornell materials science engineer Ulrich Wiesner, Ph.D., she tapped into nearly a decade of C-dot research and nanoparticle expertise.Touched personally by cancer, Wiesner was surprised by the few methods doctors had to visualize the full extent of cancer cell invasion into the body's tissues. Inspired by millions-of-years-old microscopic ocean life whose leftover silica exoskeletons cover the planet, Wiesner believed silica to be biologically safe or evolution would have discarded it long ago. He thought this inert material could be engineered in a way to look at cancer.An Unlikely Collaboration Bears FruitBradbury wanted to target tumors and selectively treat them with a variety of new drugs. When she contacted Wiesner in 2006, he and his colleagues already had synthesized small particles that could clear through the kidneys. However, they lacked specific evaluation data required by the U.S. Food and Drug Administration (FDA) for clinical use. Moreover, Bradbury wanted to develop a tumor-selective particle, so they obtained a pilot grant from the Weill Cornell Medical College Clinical and Translational Science Center (CTSC), which is supported by NIH's Clinical and Translational Science Awards (CTSA) program. CTSA institutions, like Weill Cornell, encourage collaborative teams of diverse investigators to tackle complex health issues and then translate their discoveries into practical solutions for patients.As Julianne Imperato-McGinley, M.D., principal investigator of the CTSC, explained, "This was a novel idea with tremendous potential." To fund a pilot research project, the CTSC requires collaboration among different disciplines and consortium institutions. "These investigators met and wanted a way to collaborate, fitting our requirements perfectly.""This was a seed grant," Wiesner said. "You hope that any seed you plant will grow, and that is precisely what happened here. We might never have talked otherwise."The best way for the body to eliminate particles efficiently is through the kidneys, and that means the particles must be very small. The investigators tested two sizes, 3.3 nm and 6 nm. (A nanometer [nm] is one-billionth of a meter. If the particles had a diameter of 10 nm and were lined up single file, it would take more than 2.5 million to make a line one inch long.)To be useful, the particles also needed to make whatever they cling to visible. The investigators put a tiny amount of a near-infrared fluorescent dye within the C-dot. This makes the dots light the way as they pass through the body. Silica is a very rigid material, so it squeezes the dye in the dots, making it shine much more brightly than if it were free.The first test in mice proved successful. When excited by the right light, the dots shone brightly. This made it possible to see them in the bladder to verify that the rodents excreted nearly all of them within 48 hours with no toxicity or ill effects.In successive experiments, Bradbury's colleague Oula Penate-Medina, an MSKCC nano- and radiochemist, attached radioactive iodine to the particles to make them detectable by positron emission tomography (PET) imaging. Hybrid Silica Technologies, Inc., the supplier of the particle, attached a short sequence of amino acids (the building blocks of proteins) called a cyclic RGD peptide, which binds to cancer cell surface receptors, and found that the C-dots attached to melanoma cells very effectively."This seed grant came along at the perfect time to help us get the data we needed," Bradbury said. "It funded the studies that ultimately gave us a jump-start toward the clinic." The next step was to submit an Investigational New Drug (IND) application to the FDA.Cornell University materials science engineer Ulrich Wiesner (left) and graduate students Jennifer Drewes and Kai Ma characterize the size and brightness of Cornell dots (C-dots) in research to improve cancer diagnosis and treatment. (Cornell University Photo)The Jump to the ClinicIn a textbook case of translational research, this unlikely collaboration across institutions — bridging the gulf between materials science and biomedical research — has taken multimodal C-dots through regulatory hurdles and into their first-ever clinical study with patients.With permission from the MSKCC Institutional Review Board, Bradbury is now recruiting five melanoma patients who will each receive an injection of C-dots. "We plan to take serial PET scans over a couple of days, sample blood and urine, and determine where the particles are going," explained Bradbury.Another purpose of the trial is to test the safety of C-dots and to ensure that they leave the body efficiently through the kidneys. "Once the study has been completed in these patients, we can spring forward to perform tumor-targeting," said Bradbury. "And, in future therapeutic studies, we will attach drugs or immune components to the particle."If all goes according to plan, the researchers will evaluate the use of this tumor-selective multimodal particle for clinical "sentinel node mapping," determining which lymph node is the first to receive cancer cells if a tumor already is spreading. This is a crucial first step in determining which, if any, lymph nodes must be removed. Not getting rid of enough lymph nodes can mean a patient's death due to metastatic disease. Taking too many may cause unwanted fluid accumulation, affecting a cancer survivor's quality of life."Using both optical and PET imaging, we can sensitively track the C-dots in real-time as they rapidly go to the nodes," said Bradbury. Using a hand-held fluorescent camera system, surgeons can trace the fluorescence signal from lymph nodes that contain the metastatic disease. With another device that detects radioactivity counts, they can confirm the results. Armed with this data, physicians then select treatment options. "One very attractive feature is being able to control a drug's distribution by binding it to the particles," Bradbury added. "What is not taken directly to the cancer cells will be passed out through the kidneys." This could reduce toxicity to vulnerable organs and combat cancer's notorious ability to become resistant to drugs.A Vision for the FutureWiesner is emphatic: "I want to reiterate the idea that once we know the particle is safe and working, we can move toward personalized medicine.""In the future, instead of treating patients with drugs based on their body weight," Bradbury added, "we can optimize treatment by controlling drug dosing to target the cancer. This is the essence of individualized care."Multimodal C-dots could offer this promise. Using PET to track radiolabeled drugs bound to the particle, doctors could see how much of the drug is taken up by a patient's tumor. Coupled with other key tumor characteristics, physicians could select dosing regimens designed for treating individual tumors. In addition, surgeons could use the technology to see where metastatic disease has spread and target therapies based on the cancer's stage."There is a lot of enthusiasm among clinicians for using such multimodal platforms," said Bradbury. "This particle will make it possible to improve both diagnostics and treatment."Bradbury believes CTSC pilot funding was essential, explaining that even the best idea will not be funded without some pilot data to back it up. "It is not typical for something like this to go into the clinic," she said. "The CTSC award allowed us to fund our approach and complete the essential studies needed for the IND proposal within a two-year period." She plans to use the CTSC to help her coordinate multicenter patient studies as her research progresses."This is a beautiful example of what the CTSC exists to do," Imperato-McGinley added. "We try to encourage collaborative, multidisciplinary research because the fruitful mixture of ideas and approaches from different disciplines works. For the two of them to get this far in such a short time is amazing." Posted March 2012 | ||||||||
| 580 | Designing Solutions to Improve Health for All | In the event of a severe influenza pandemic, 700,000 U.S. residents would be at risk of dying simply because of a shortage of ventilators to keep people alive and breathing when their respiratory systems fail. In developing countries, the situation could be far worse. Because ventilators can cost up to $40,000, clinics in these countries find it impractical to purchase enough of these life-saving devices for daily patient care and hospitals find it nearly impossible to stockpile them for emergencies. This is the kind of problem that fellows in Stanford University's Biodesign program have been tackling for the past decade. Biodesign brings together graduate students from the medical, engineering and business fields to create innovative products that fill unmet medical needs and ultimately improve patient health. Biodesign fellows are funded in part by the Stanford Center for Clinical and Translational Education and Research (known as Spectrum), which is supported by NCATS through its Clinical and Translational Science Awards (CTSA) program. "Biodesign specializes in 'inventorship' — a new skill that can be refined and honed," said Spectrum director Harry Greenberg. "At its heart, Biodesign is a program that teaches people to be inventors, and this effort has been immensely successful." Breathing New Life into Old Technology When Matt Callaghan, M.D., and a team of Biodesign fellows learned of the need for an affordable ventilator, they took matters into their own hands and invented one. Callaghan was a surgical resident taking part in pandemic planning at his hospital when he recognized that a more economical, more efficient ventilator could potentially save hundreds of thousands of lives. The OneBreath ventilator was designed by a team in Stanford University's Biodesign program for use in emergency pandemic situations and for patient care in resource-poor countries. Developers (left to right) are Matt Callaghan, Larry Miller, Frederick Winston Blond, William Bishop and Dhruv Boddupolli. (Steve Fisch Photography) The unique training program at Biodesign, with its systematic approach to invention and design, was the ideal place to bring such a product to life. Biodesign's method moves product development through three critical steps: need identification, concept development and business planning. Biodesign fellows first spend time in clinical observation and study of a biomedical need. "The innovation process starts purely with a detailed understanding of an important clinical need," said Paul Yock, M.D., Biodesign director, leader of the Spectrum innovations and pilot units and co-lead of its core resources. "We say that a well-characterized need is the DNA of a good invention. This emphasis on finding and characterizing clinical needs up front is one of the most important differences between our training process and most research programs." Biodesign fellows design and build prototype devices with the potential to fill the identified medical gap. Callaghan's prototype ventilator, called OneBreath, is less expensive than existing devices and easier for novice users to operate. It also is portable and effective, two crucial features for use in emergency pandemic situations, in rural areas and in the terrains of resource-poor countries. Until now, all of these features had not been found together in one device. Manufacturing costs for OneBreath are estimated at $800 per unit, and the device features technology that emphasizes efficiency. Most ventilators use expensive air flow sensors and complex motorized equipment, but OneBreath can be constructed with just 12 parts instead of hundreds. It uses a basic pressure sensor, like those found in blood-pressure meters, to measure air pressure and volume in a patient's airway as a compressor forces air into the chest. Specially designed software interprets the data and directs the ventilator to supply air through a valve system. If a patient starts to breathe on his own again, the device supplies less air, which enables the patient to gradually recover and to fully breathe independently of the ventilator. Callaghan discovered through field research in India and China that factors other than price must be considered when designing a ventilator for use in developing countries. "You can't just de-feature existing medical equipment and sell a stripped-down version to each country. Patients are sick there like they are here, but conditions and resources are all different," he said. For example, in developing countries, ventilators often need to be carried into rural areas, and hospitals generally do not have staff trained to use the equipment. OneBreath was built for easy use, with a simple interface and instructions printed on the back. It can run on a 12-volt battery for up to 12 hours in case of a power outage, and because it is smaller than a toolbox, it can easily be carried long distances. These same characteristics also make OneBreath useful in large-scale disasters in more developed countries, such as the U.S. Now a postdoctoral fellow at Biodesign, Callaghan is working with his team through final testing as OneBreath moves toward commercial release. With direct funding from the Stanford Coulter Translational Research Partners program, the Biodesign team is collaborating with business students to ensure that OneBreath will have the greatest impact when it makes the transition from the drawing board to the marketplace. Yock has witnessed the success of the program's multidisciplinary, team-based approach as innovative projects like OneBreath move from mere idea to manufactured product. "These projects simply would not have come into existence without the close interplay of engineers, physicians and business experts who together can help navigate the complex and difficult process of technology transfer in the biomedical field," he said. "CTSAs are designed to enable these types of connections," said Anthony Hayward, senior advisor for translational research to the NCATS director. Walking Into New Territory Another Biodesign project team, led by Thomas Andriacchi, Ph.D., also has developed an important new medical device after responding to a request to design a low-cost prosthetic knee. High-end titanium knee joints can cost from $10,000 to $100,000. This cost is far beyond the reach of most of the world's 20 million amputees. Four out of five amputees live in the developing world, and many of them are coping with the impact of war and diseases like diabetes. Looking for a way to help these patients, the Jaipur Organization, a nonprofit group based in India, asked Biodesign to create a low-cost prosthetic knee. Andriacchi presented the idea as a project for mechanical engineering students in his Medical Device Design class and selected five students to compose the JaipurKnee design team. With additional funding from Jaipur Organization supporter Armand Neukermans, the design team developed, built and then tested a prototype prosthetic knee in just 20 weeks. The result was the JaipurKnee, a $20 prosthetic limb designed specifically for amputees in resource-poor countries, with a target market of India's 1.65 million above-knee amputees. The JaipurKnee is a new prosthesis that costs only $20 to manufacture and is designed specifically for use by amputees in resource-poor countries. The device was invented by team members (left to right) Angelo Szychowski, Joel Sadler and Eric Thorsell. Ayo Roberts and Ellis Garai, also part of the design team, are not pictured. (Stanford Biodesign Photo/Christine Kurihara) Existing lower cost models were built on a single axis joint, like a door hinge, which often buckled under the weight of its wearer and were unstable when used on uneven terrain. The JaipurKnee has a self-lubricating joint for greater flexibility and is easier for patients to use because it is designed to mimic the natural motion of the human gait. "The students were highly motivated, and the number of hours they put in far exceeded the credit hours they received," said Andriacchi. In fact, two students from Andriacchi's design group, Joel Sadler and Eric Thorsell, continued to push the JaipurKnee into manufacturing after the course ended. The students have since formed a company called re:motion designs, with the goal of scaling up production of the JaipurKnee in India. So far, they have distributed more than 2,000 knees to amputees. While the company is ramping up knee production in India, it is also adapting the design for use in other parts of the world. Ari Chaney, Biodesign's executive director for technical translation and program manager for the Spectrum innovations and pilots unit, credits CTSA support with enabling innovative projects like the JaipurKnee and OneBreath to successfully move from concept to application. "This funding enables promising projects to prove their concepts while still in the academic setting," said Chaney. "That's valuable because it's often difficult to successfully navigate from research to commercial success. Proving that the technology works with steps such as prototyping, detailed design and clinical testing enables these projects to attract support and external funding," he added. Forging New Collaborations The success of projects like OneBreath and the JaipurKnee has helped launch the Stanford Global Health Consortium for Innovation, Design, Evaluation and Action (C-IDEA), a new initiative of Stanford University that will integrate the efforts of four of Stanford's global health programs. C-IDEA is funded by the American Recovery and Reinvestment Act through an NIH Director's award. "We will focus on innovative design of diagnostics, drugs and devices for global health that are scalable, have high impact, and can be implemented and commercialized," said Michele Barry, M.D., FACP, Stanford's senior associate dean for global health. The efforts of Biodesign will continue to spur innovations for global health that otherwise might not exist. Posted March 2012 | ||||||||
| 579 | Stephen Groft, Champion of Rare Diseases Research, Retires | Through his work with a community that often feels isolated, Stephen C. Groft, Pharm.D., has helped give thousands of rare disease patients and their families renewed hope and a collective voice. A public servant for more than four decades and a tireless advocate for rare diseases research, Groft is recognized by many as a luminary and true champion of rare diseases research. On Feb. 8, 2014, Groft will retire from his current position as director of NCATS’ Office of Rare Diseases Research (ORDR). He leaves a 30-year legacy of advancing rare diseases research and improving the lives of patients with these conditions. Pamela M. McInnes, D.D.S., M.Sc.(Dent.), NCATS deputy director, will serve as acting director of ORDR during the search for a new director. Groft’s journey, which includes many major milestones, started on a personal note. "Growing up in the 1950s, I had friends and neighbors who were stricken with diseases that had few or no effective treatments," Groft said. "Some of the diseases of our time that I witnessed firsthand included cystic fibrosis, leukemia, brain tumors, Marfan syndrome, muscular dystrophy, cerebral palsy, polio, multiple sclerosis and Parkinson’s disease." These personal connections led him to a career at the Food and Drug Administration (FDA) and NIH, where he worked to prioritize rare diseases research and orphan product development. Along the way, he also served in a variety of advisory roles to national leaders, including congressional and White House representatives, allowing him to influence the national agenda on rare diseases research. "The creation of NCATS is in many ways a validation of Steve’s work over the past 30 years," said NCATS Director Christopher P. Austin, M.D. "Rare diseases are no longer a curiosity on the periphery of the biomedical research enterprise. They now are central to the research agenda, and that is due in large part to Steve’s vision, dedication and effectiveness." Rare disease research is a crucial priority for NCATS. The Center fosters collaborative efforts with multidisciplinary research teams to develop new approaches to drug discovery for rare diseases. The Early Years Groft began his career in 1968 as a small-town pharmacist in Pennsylvania, helping patients understand their conditions and medications and building connections that would influence his lifelong focus on rare diseases. His policy-related efforts began in 1982 at the FDA Office of Orphan Products, a division dedicated to advancing the evaluation and development of therapeutics for the diagnosis and treatment of rare diseases. Throughout the 1980s, Groft served in a variety of leadership roles to help advance the national research and drug development agendas for rare diseases, beginning with his support of the Orphan Drug Act (ODA) in 1983. Prior to the act, pharmaceutical companies often neglected therapeutics for rare diseases because the cost of research and development frequently outweighed the return on investment for products that only a small number of people needed. The ODA provided financial and regulatory incentives to pharmaceutical companies to make production of so-called “orphan drugs” more cost-effective. Since the law’s enactment, the FDA has approved more than 450 orphan products, and the rate of approval has increased: In 1983, two orphan products were approved; in 2012, 26 were approved. Changing U.S. Policy and Practice Groft received the Social Security Administration Commissioner's Appreciation Award at a Capitol Hill event in December 2012 for his work to assist rare disease patients who seek disability benefits. Recognizing that more was needed than industry incentives, Congress established the Department of Health and Human Services’ (HHS’) National Commission on Orphan Diseases in 1985, charging it with identifying gaps in rare diseases research, patient care, regulatory issues, insurance coverage and related areas. In the HHS Office of the Assistant Secretary for Health, Groft served as executive director of the Commission from 1987 to 1989. The group’s efforts culminated in a 1989 report to Congress that led to the establishment of ORDR in the Office of the Director at NIH. The ORDR mission was — and remains — to identify, stimulate, coordinate and support research to respond to the needs of patients with rare diseases. Groft became ORDR director in 1993, remaining in the post through the office’s 2011 transition to NCATS. During his more than two decades as ORDR director, Groft worked with legislators, regulators, researchers, pharmaceutical representatives, patients, families and patient advocacy groups to build a community that could address the needs of rare disease patients more effectively. His accomplishments include: 1995: Scientists studying rare diseases often do so in isolation and unaware of each other’s work. Recognizing the need for these researchers to collaborate and share knowledge, Groft and other ORDR staff initiated a scientific conferences program with the 27 Institutes and Centers (ICs) at NIH. Since then, more than 1,200 ORDR-supported research conferences and workshops have taken place. 2000: Groft contributed research protocols to NIH’s ClinicalTrials.gov — a Web-based resource that provides easy access to publicly and privately supported clinical studies — expanding the system to include a broader range of diseases and conditions. 2002: Groft collaborated with the National Human Genome Research Institute (NHGRI) to establish the Genetic and Rare Diseases Information Center, a public forum providing information about more than 5,000 rare and genetic diseases to patients and families. 2003: Groft led ORDR’s efforts in establishing the Rare Diseases Clinical Research Network (RDCRN), which enables collaborative, trans-NIH clinical research on causes, prevention, outcomes and treatments of rare diseases. Several RDCRN researchers have developed successful therapeutic products that received FDA approval. 2008: Groft, along with NHGRI, the NIH Clinical Center and other NIH ICs, helped create the trans-NIH, multidisciplinary Undiagnosed Diseases Program. This clinical research initiative is designed to advance medical knowledge about rare, undiagnosed diseases and to provide answers to patients who suffer from conditions with no diagnosis. 2012: Groft led ORDR in establishing the International Rare Diseases Research Consortium to encourage international collaboration in rare diseases research. Groft has received multiple awards in recognition of his decades of hard work to advance rare diseases research and therapeutics. These awards include the 2013 Henri Termeer Lifetime Achievement Award from the Global Genes | RARE Project, the 2012 Social Security Administration Commissioner’s Appreciation Award for Groft’s work to assist rare disease patients who seek disability benefits, and the National Organization for Rare Disorders’ Medal of Honor for “Vision and Pioneering Guidance” in rare diseases research. At left, Groft and his wife Jan at the Global Genes | RARE Project Tribute to Champions of Hope Awards Ceremony in September 2013; at right, Groft received the Medal of Honor for "Vision and Pioneering Guidance" at the National Organization for Rare Disorders' 30th Anniversary Celebration in May 2013. Looking to the Future Groft’s departure coincides with a time of unprecedented optimism and promise for the understanding and treatment of rare diseases. Major advances in small molecule therapies, regenerative medicine and nanotechnology, whole-genome sequencing, and personalized medicine hold enormous potential for improving the lives of patients with rare diseases. NCATS will pursue these opportunities with undiminished energy and an aim to achieve Groft’s vision that every rare disease be understood and effectively treated. I’ve never before seen so many opportunities and research activities related to rare diseases and orphan products and so many possibilities for therapeutic development,” Groft said. “We are on the cusp of transformative and revolutionary breakthroughs, and I anticipate that I will be hearing more about NCATS’ role in these areas in the years to come.” Posted February 2014 | ||||||||
| 577 | Petra Kaufmann Joins NCATS as Clinical Innovation Director | Petra Kaufmann, M.D., M.Sc., will head the NCATS Division of Clinical Innovation beginning May 4, 2014. Her new role will include overseeing the Clinical and Translational Science Awards (CTSA) program with the aim of improving the effectiveness and efficiency of the process of translation from scientific discovery through clinical research to improved health outcomes. Kaufmann currently serves as director of the Office of Clinical Research at NIH's National Institute of Neurological Disorders and Stroke (NINDS). "Following a comprehensive national search, I am delighted that Petra is joining the NCATS leadership team,” said NCATS Director Christopher P. Austin, M.D. “Her record of expertise and accomplishment across the translational sciences — from basic research to clinical studies — makes her ideally suited to lead our clinical innovation efforts." Prior to joining NINDS in 2009, Kaufmann was a tenured associate professor of neurology at Columbia University in New York, where she worked in the neuromuscular division, electromyography laboratories and pediatric neuromuscular clinic. At Columbia, she gained experience with the CTSA program by serving on several committees within the Irving Institute for Clinical and Translational Research, including the Clinical Research Resource Advisory Committee. At NINDS, Kaufmann recognized the need for clinical research infrastructure and established NeuroNEXT, an academic research trial network for Phase II clinical trials across a wide range of neurological diseases, as well as StrokeNET, a Phase II and III clinical trial network for stroke. These networks aim to accelerate clinical research by including a central institutional review board and pre-negotiated master trials agreements. They also foster public-private partnerships by engaging industry and patient groups. Kaufmann also led efforts at NINDS to engage patients earlier in the clinical research process by soliciting their active input in protocol development as well as in the implementation and safety oversight of clinical trials. "I enjoyed my work in the lab and the clinic,” Kauffman said. “I’m excited for the opportunity to work in the translational sciences field that aims to bridge these disciplines for the greater good of patients in need." Kaufmann will maintain her current adjunct academic appointment at Columbia University, privileges at the NIH Clinical Center and patient care at the Muscular Dystrophy Association Clinic at Children's National Medical Center. She earned her M.D. from the University of Bonn in Germany and her M.Sc. in biostatistics from Columbia’s Mailman School of Public Health, and she trained in neurology at Columbia University. Posted April 2014 | ||||||||
| 575 | NCATS Launches Chemical Toxicity Data Model Competition | NCATS' Toxicology in the 21st Century (Tox21) Data Challenge 2014 is a crowdsourcing competition to develop computational models that can better predict chemical toxicity. The Tox21 initiative is designed to improve current toxicity assessment methods, which are slow and costly. Participants who submit the winning models, as judged by the Tox21 Data Challenge Committee, will have the opportunity to submit a paper for publication in a special thematic issue of Frontiers in Environmental Science. NCATS also will recognize winning submissions in national communications, including on the NCATS website and in social media channels. Selected models will become part of the Tox21 program arsenal of tools that help researchers assess how various chemicals might disrupt biological processes in the human body and lead to negative health effects. Register for the challenge today. The model submission deadline is Nov. 14, 2014, 11:59 p.m. ET. NCATS will showcase the winning models in January 2015. Tox 21 is a collaborative effort among NIH, the Environmental Protection Agency (EPA), and the Food and Drug Administration. NIH partners include NCATS and the National Toxicology Program, administered by the National Institute of Environmental Health Sciences. Tox21 scientists currently are testing a library of more than 10,000 chemical compounds (Tox21 10K) in NCATS' high-throughput (large-scale) robotic screening system. To date, the team has produced nearly 50 million data points from screening the Tox21 10K library against cell-based assays (tests). Data generated from 12 of these assays form the basis of the 2014 challenge. "The Tox21 program is a wonderful example of what can be accomplished when government agencies join forces and pool resources," said NCATS Director Christopher P. Austin, M.D. "Our researchers have generated more data about chemical toxicity than we can realistically analyze and understand without additional collaboration. Similar to many other large-scale scientific endeavors that generate public data, we have created the 2014 challenge to crowdsource the best predictive models from researchers across the globe." All Tox21 data are available to the public through chemical toxicity databases supported by NIH and the EPA. In addition, NCATS created a free Tox21 chemical inventory browser to provide researchers with additional information about the 10,000 chemicals in the library. Posted July 2014 | ||||||||
| 573 | NCATS Bridges Research Gaps in Developing Treatments for Diabetes-Related Blindness and Severe Heart Attacks | NCATS is supporting two new Bridging Interventional Development Gaps (BrIDGs) projects selected during the 2014 program application solicitation. Through BrIDGs, NCATS provides scientists with access to preclinical drug development resources such as toxicology studies. One of the new projects is aimed at developing a therapy for diabetic keratopathy, a condition that often leads to blindness. The disease occurs in about one-half to two-thirds of people with diabetes, producing chronic injury and damage to the cornea, the clear outer part of the eye. Diabetic keratopathy frequently is unresponsive to conventional treatments. The second project is focused on a treatment for ST-segment-elevation myocardial infarction (STEMI), a severe type of heart attack. Each year, approximately 160,000 people in the United States suffer STEMI. Although emergency medical service providers commonly give heart attack victims aspirin and other treatments during transport to the hospital, these interventions are not successful in many cases, and some patients die prior to reaching the hospital. "The resources NCATS provides through the BrIDGs program — such as to evaluate the safety of candidate therapeutics — can make the difference in whether a promising new treatment reaches clinical trials," said Christopher P. Austin, M.D., NCATS director. "BrIDGs provides a unique and effective path through some of the most difficult phases of translational development." To be eligible for the BrIDGs program, projects must have been proven effective in a disease model. Researchers often apply to BrIDGs because they have hit a roadblock and need additional expertise or lack other resources. Rather than funding successful applicants directly, BrIDGs operates through collaborative project teams, which provide access to NCATS translational expertise and preclinical services contracts at no cost to the collaborating researchers. A key BrIDGs project goal is to enable the applicant to submit an Investigational New Drug (IND) application to the U.S. Food and Drug Administration (FDA) to begin human clinical trials. To date, BrIDGs scientists have generated data to support 15 INDs submitted to the FDA, as well as one clinical trial application to Health Canada. Thirteen of the 16 projects have been evaluated in clinical trials. Four BrIDGs-supported therapeutic agents have gone as far as Phase II clinical trials, in which researchers provide an experimental therapy to a group of patients to evaluate its safety and effectiveness. Eight compounds have been licensed to third-party investors for further development during or after their progression through the BrIDGs program. Posted October 2014 | ||||||||
| 572 | NCATS Announces Tox21 Data Challenge Winners | On Jan. 26, 2015, NCATS announced the winners of the Toxicology in the 21st Century (Tox21) Data Challenge 2014, a crowdsourcing competition that attracted contestants from 18 countries to design computational models to better predict chemical toxicity. Tox21 is a collaborative effort among NCATS and the National Institute of Environmental Health Sciences, Environmental Protection Agency and Food and Drug Administration to improve current methods scientists use to evaluate environmental chemicals and develop new medicines. There are hundreds of thousands of chemicals that could be harmful to humans, and testing each one separately would be expensive and virtually impossible. Computational models — such as those submitted in response to this challenge — can predict whether a substance may be toxic by interrupting certain biological pathways based on the chemical structure. Combining these models with the knowledge already gained from Tox21 screening data can help scientists better prioritize chemicals for further toxicological testing, saving both time and money. Challenge participants used data from nuclear receptor signaling and stress pathway assays (tests) run against Tox21’s 10,000-compound library to build models and look for structure-activity relationships. The models from the seven winning teams will become part of the Tox21 program’s arsenal of tools that help researchers assess how various chemicals might disrupt biological processes in the human body and lead to negative health effects. All displayed very good predictive power, achieving greater than 80 percent accuracy, with several models exceeding 90 percent accuracy. “The high quality of the models gives us confidence that they can be applied to identify those chemicals that have the most potential for toxicity, enabling us to prioritize them for further evaluation,” said Anton Simeonov, Ph.D., NCATS acting scientific director. “Moreover, since the models are dependent on high-quality data and the top ones performed so well, this outcome further validates the value of our Tox21 screening efforts.” The winners are: Team Name Challenge Assay(s) Team Member(s) Organization(s) Bioinf @JKU Grand Challenge (all 12 assays) Stress Response Panel Aryl Hydrocarbon Receptor Nuclear Factor (Erythroid-Derived 2)-like 2/Antioxidant Responsive Element Günter Klambauer, Ph.D. Sepp Hochreiter, Ph.D. Andreas Mayr, M.Sc. Thomas Unterthiner, M.Sc. Institute of Bioinformatics, Johannes Kepler University Linz, Austria Bioinf @JKU-ensemble1 Estrogen Receptor Alpha, Full Length Heat Shock Factor Response Element Günter Klambauer, Ph.D. Sepp Hochreiter, Ph.D. Andreas Mayr, M.Sc. Thomas Unterthiner, M.Sc. Herbert Zaunmair Institute of Bioinformatics, Johannes Kepler University Linz, Austria Bioinf @JKU-ensemble3 Androgen Receptor, Ligand Binding Domain Günter Klambauer, Ph.D. Sepp Hochreiter, Ph.D. Ulrich Bodenhofer, Ph.D. Andreas Mayr, M.Sc. Thomas Unterthiner, M.Sc. Institute of Bioinformatics, Johannes Kepler University Linz, Austria Bioinf @JKU-ensemble4 Nuclear Receptor Signaling Panel Peroxisome Proliferator-Activated Receptor Gamma Günter Klambauer, Ph.D. Sepp Hochreiter, Ph.D. Birgit Hauer Andreas Mayr, M.Sc. Thomas Unterthiner, M.Sc. Institute of Bioinformatics, Johannes Kepler University Linz, Austria AMAZIZ ATAD5 Mitochondrial Membrane Potential Ahmed M. Abdelaziz Sayed Technical University of Munich Dmlab Androgen Receptor, Full Length Aromatase p53 Gergő Barta, M.Sc. Budapest University of Technology and Economics Microsomes Estrogen Receptor Alpha, Ligand Binding Domain Yoshihiro Uesawa, Ph.D. Department of Clinical Pharmaceutics, Meiji Pharmaceutical University |
Last updated on