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| 292 | cGMP Synthesis of the Selective Kappa Opioid Receptor Antagonist JDTic | Cocaine is one of the most addictive and most physically dangerous of “recreational” drugs, yet in 2012, 14.5 percent of Americans over age 12 reported having used it. Cocaine users have a higher risk of stroke and heart attack because the drug increases both heart rate and blood pressure. The drug becomes difficult to resist by increasing the level of dopamine, a brain-signaling chemical (neurotransmitter), in the brain. This flood of dopamine is what causes the pleasurable “high” from cocaine. Long-term use changes the brain’s reward system and causes brain damage. For those who become addicted, craving for the drug can last for years after they have stopped taking it, and stress or depression can trigger a relapse. These researchers are developing a drug to treat cocaine relapse by blocking a receptor in the brain that binds to cocaine, thus decreasing the craving for the substance. Scientific Synopsis JDTic is a highly potent and selective antagonist of the opioid kappa receptor. Evidence currently available indicates that by blocking the action of the endogenous peptide dynorphin at the kappa receptor, JDTic offers a means of treating several diseases that are of importance to NIH, including drug abuse (cocaine relapse), depression and schizophrenia. The compound is soluble, orally active and nontoxic. JDTic demonstrates dose-dependent kappa opioid receptor antagonist behavior in several animal models (rats and monkeys), including stress-induced relapse to cocaine, Porsolt forced swim test, and reversal of kappa agonist-induced diuresis and analgesia. Coupled with its long duration of action, the information presently available suggests that JDTic represents a safe and effective means of preventing relapse to cocaine use even in a typically noncompliant patient group. Lead Collaborator RTI International, Research Triangle Park, North Carolina F. Ivy Carroll, Ph.D. Public Health Impact JDTic is effective in simultaneously addressing stress and depression, two of the predominant factors influencing relapse to cocaine use. Support of this project will fill the gaps between other resources made available by NIH to advance this agent toward an Investigational New Drug (IND) application. Outcomes Work on this project is complete. Additional preclinical development was supported by the National Institute on Drug Abuse. The investigator successfully filed an IND application using BrIDGs data and material and initiated clinical testing. Project Details Synthesis of Good Manufacturing Practice (GMP) Material | ||||||||
| 291 | 2012 Director’s Messages | Select a 2012 message from the list below: April 24, 2012: Acting Director’s Message Aug. 21, 2012: Acting Director’s Message Sept. 24, 2012: Director’s Message Dec. 14, 2012: Director’s Message April 24, 2012: Acting Director’s Message Welcome to the National Center for Advancing Translational Sciences at the NIH. Our mission is to catalyze the generation of innovative methods and technologies that enhance the development, testing, and implementation of diagnostics and therapeutics across a wide range of human diseases and conditions. Advances in these areas will enable others in both the public and private sectors to develop drugs and diagnostics more efficiently for any number of human diseases — ultimately accelerating the pace in which new therapeutics are delivered to the patients who need them. In establishing the Center, NIH involved internal and external stakeholders to guide its research agenda and pinpoint priorities. A group of NIH Institute and Center directors, including those most involved in translational research, emphasized the need for a translational focus that would provide tools and resources to facilitate research across NIH. Additionally, a working group of the NIH Advisory Committee to the Director, comprised of experts from industry, private equity firms, nonprofit organizations and academia, identified a need to streamline translational sciences. Priority areas included: Research on biomarkers. Predictive toxicity. Target validation. Regulatory science. De-risking the therapeutic pipeline. Through this guidance, NCATS is ensuring that its research efforts are not duplicating the efforts of others at NIH or competing with industry. As such, our highest priority is to reduce, remove or bypass significant hurdles across the continuum of translational research, particularly in the priority areas indicated above by our stakeholders. As a result, the NCATS research agenda reflects this goal, and our current budget request is aligned with these priorities. All of us at NCATS are excited about the opportunities on the horizon to advance translational sciences. As you explore our new website, check back often to learn about the Center’s latest news, like us on Facebook and join our Twitter feed. As always, we welcome your feedback on ways to improve the site. Thomas R. Insel, M.D. Acting Director National Center for Advancing Translational Sciences Aug. 21, 2012: Acting Director’s Message Welcome to the National Center for Advancing Translational Sciences at NIH. Our mission is to catalyze the generation of innovative methods and technologies that enhance the development, testing, and implementation of diagnostics and therapeutics across a wide range of human diseases and conditions. Advances in these areas will enable others in the public and private sectors to develop drugs and diagnostics more efficiently for any number of diseases — ultimately accelerating the pace at which new treatments are delivered to the patients who need them. Already, NCATS has become a hub of innovation for translational sciences. Since its creation in December 2011, the Center has launched several major research initiatives, cultivated promising strategic partnerships, and established a presence at NIH and in the community — all while standing up a brand new center. Several of these early accomplishments emphasize the Center’s research priorities, including: Issuing a funding opportunity to support a national network of clinical and translational research institutions Creating new tools for predicting drug toxicity Developing innovative partnerships to find new uses for existing medications All of us at NCATS are excited about the opportunities on the horizon to advance translational sciences. Check back often to learn about the Center’s latest news and accomplishments, like us on Facebook and join our Twitter feed. As always, we welcome your feedback. Thomas R. Insel, M.D. Acting Director National Center for Advancing Translational Sciences Sept. 24, 2012: Director’s Message Welcome to the National Center for Advancing Translational Sciences ― NIH’s newest Center. As NCATS’ new director, I am excited to lead the Center on its mission to catalyze innovations aimed at enhancing the development, testing and implementation of diagnostics and therapeutics across a wide range of human diseases and conditions. Advances in these areas will enable others in the public and private sectors to develop drugs and diagnostics more efficiently for any number of diseases, ultimately accelerating the pace at which new treatments are delivered to the patients who need them. It is an exciting time for science. Today, we know so much about the molecular basis of disease and by pairing this knowledge with advances in technology and with expert partners, we can transform the translational research process into an efficient and collaborative enterprise. By focusing on commonalities across diseases and organ systems, we can complement the work of other NIH Institutes and Centers as well as that of our pharmaceutical, foundation and advocacy partners. Already, NCATS has become a hub of innovation for translational sciences. Since December 2011, the Center has launched several major research initiatives, cultivated promising strategic partnerships, and established a presence at NIH and in the community — all while standing up a brand new center. These milestones include: Establishing a formal NCATS Advisory Council and Cures Acceleration Network Review Board and holding inaugural meetings; Supporting a national network of clinical and translational research institutions; Granting awards to scientists to create new tools for predicting drug toxicity, such as 3-D human tissue chips; and Developing innovative partnerships to find new uses for existing medications. These accomplishments would not have been possible without extraordinary leadership from my predecessor, Thomas R. Insel, M.D., who has been serving as the NCATS acting director since our launch. He established a strong foundation on which to build, and I look forward to working with a tremendously talented and supportive team to continue advancing our translational medicine programs and initiatives. Check back often to learn about the Center’s latest news and accomplishments, like us on Facebook, join our Twitter feed, and subscribe to our e-newsletter. As always, we welcome your feedback. Christopher P. Austin, M.D. Director National Center for Advancing Translational Sciences Dec. 14, 2012: Director’s Message As NIH’s newest Center, NCATS is moving boldly toward establishing a strategic vision that will transform the translational process for the benefit of science and patients. We are establishing an organization that emphasizes innovation and deliverables and relies on the power of data to develop, demonstrate and disseminate improvements in translational science. Recently, I have been connecting with a wide spectrum of those in the research ecosystem who are important to NCATS’ mission. In addition to scientists and other staff throughout NCATS, I am talking with each of my 26 fellow NIH Institute and Center directors as well as representatives from patient advocacy organizations, biotechnology and pharmaceutical companies, foundations, and the U.S. Food and Drug Administration and other government agencies. In October, I had the opportunity to meet and exchange ideas with investigators from the Clinical and Translational Science Awards (CTSA) program during their national consortium meetings, and I’ve also been visiting a number of CTSA sites throughout the country. In November, I joined our partners at FasterCures to discuss the need for teamwork in translation (see video below). In December, I engaged in discussions with many of NCATS’ stakeholders at the center’s first policy workshop as a way for us to better understand how policy research and analysis can inform translational research. YouTube embed video: https://www.youtube.com/watch?v=Ud9YnviTxcM Right-click to download a transcript (5KB) In all of these conversations, I am seeking advice on NCATS’ priorities, that is, the most urgent and pervasive roadblocks in the translation of fundamental scientific discoveries into tangible benefits for human health. Using this input, I am formulating NCATS’ initial strategic priorities and directions, which are focused on making the translational research process more efficient, science-based and predictive. I have been tremendously gratified by the outpouring of goodwill, offers of collaboration and ideas provided. I look forward to continuing these frank and productive conversations in the near future. Please check our website often to learn about NCATS’ latest news and accomplishments. Stay informed by subscribing to our e-newsletter and listserv, like us on Facebook, join our Twitter feed, and share your feedback. Christopher P. Austin, M.D. Director National Center for Advancing Translational Sciences | ||||||||
| 290 | Director’s Biography | .caption-and-calloutbox-container { float: left; display: block; width: 32%; margin-right: 1.5rem; margin-bottom: 1.5rem; margin-left: 0; } .callout-box { max-width: 100%; width: auto; height: auto; border: 2px solid hsla(0, 0%, 0%, 0.5); border-radius: 5px; background-color: #f2f2ed; padding: 10px; float: left; } .caption-left-sm { width: 100% !important; } .img-responsive { height: auto; } Image Credit: National Center for Advancing Translational Sciences Link to high-res photo.Sign up to receive monthly email messages from the NCATS director on center activities, events and more.Joni L. Rutter, Ph.D. Director National Center for Advancing Translational Sciences National Institutes of HealthJoni L. Rutter, Ph.D., is the director of the National Center for Advancing Translational Sciences (NCATS) at the National Institutes of Health (NIH). She oversees the planning and execution of the center’s complex, multifaceted programs that aim to overcome scientific and operational barriers slowing the development and delivery of new treatments and other health solutions.Under Rutter’s direction, NCATS supports new tools and approaches to make each step in the translational process more effective and efficient. A key goal is to speed research across a range of diseases, with a particular focus on rare diseases. By advancing the science of translation, NCATS helps turn promising research discoveries into real-world applications that improve people’s health.In her prior role as the NCATS deputy director, Rutter worked with colleagues from government, academia, industry and nonprofit patient organizations to create robust interactions with NCATS programs.Before joining NCATS, Rutter was the director of scientific programs within the All of Us Research Program. She led scientific programmatic development and implementation efforts to build a national research cohort of 1 million or more U.S. participants to advance precision medicine.While at NIH, she also led the Division of Neuroscience and Behavior at the National Institute on Drug Abuse (NIDA). In this role, she developed and coordinated research on basic and clinical neuroscience, brain and behavioral development, genetics, epigenetics, computational neuroscience, bioinformatics, and drug discovery. Rutter also coordinated the NIDA Genetics Consortium and biospecimen repository.During her career, Rutter has earned a national and international reputation for her diverse and unique expertise via her journal publications. She has received several scientific achievement awards, including the 2022 Rare Disease Legislative Advocates–RareVoice Award for Federal Advocacy and the 2022 FedHealthIT–Women in Leadership Impact Award.Rutter received her Ph.D. from the Department of Pharmacology and Toxicology, Dartmouth Medical School, Hanover, New Hampshire, and completed a fellowship at the National Cancer Institute within the Division of Cancer Epidemiology and Genetics. | Director’s Biography | Director’s Biography | ||||||
| 289 | Director’s Corner | April 19, 2023: NCATS’ New Strategic Plan Will Chart a Path for Realizing Our Audacious Goals Image Credit: National Center for Advancing Translational Sciences Link to high-res photo. Read about the NCATS director. Sign up to receive email updates from Dr. Rutter on topics of interest to NCATS’ stakeholder community. Last year, I laid out a set of audacious goals for the next 10 years to support NCATS’ vision of more treatments for all people more quickly. These goals will be our guide for building the center’s next strategic plan, and we need your help. NCATS’ mission is to turn research observations into health solutions through translational science. We define translational science as the field that generates scientific and operational innovations that solve long-standing challenges along the translational research pipeline. Over the past decade, we have addressed many of these research bottlenecks through our programs and initiatives that leverage principles of effective translational science. As we strive for our audacious goals, we must work even better and more efficiently. The NCATS strategic plan will be an important tool for doing that. The plan will reflect NCATS’ priorities, and I hope many of yours. Our translational science community has always been the key to our success, and we want to work with you to co-build a plan for NCATS’ future that we can all support and carry forward. We would like input on meaningful and measurable ways we can make our audacious goals a reality. During the strategic planning process, we will explore how data science; policy development; team science; training; diversity, equity, inclusion, and accessibility; and other cross-cutting areas can help NCATS make a bigger impact in support of more treatments for all people more quickly. Your input also will help us identify what is missing from our current portfolio, where we need to do better, and how we measure success. While the strategic plan will cover 2024-2029, it also will support our decadal goals by including ideas for longer-term efforts that we could start within this 5-year timeframe. We want to tackle big problems in translation, so our plan needs to be flexible. It must allow us to “fail forward” and adjust any approaches that are not working. Similarly, we might need to pivot to address emerging concerns as we did during the COVID-19 pandemic or find translational science solutions for new or unmet needs with great potential to improve health. Hearing from you now will help inform what we do in the future, so please make your voice heard by attending one of our strategic planning roundtable discussions: Tuesday, May 9, from 12:00 to 1:30 p.m. EDT Wednesday, May 10, from 9:30 to 11:00 a.m. EDT These will be the first of different opportunities to guide the NCATS strategic plan. We are planning discussions with the NCATS Advisory Council at the public meeting on May 25 and will post a request for information this summer. The final plan will be launched early next year. For real-time strategic planning updates via email, please sign up for my stakeholder listserv. Your partner in science and health, Joni L. Rutter, Ph.D. Director National Center for Advancing Translational Sciences | Joni Rutter shares her goals for NCATS’ next strategic plan and ways the translational science community can co-build it. | /sites/default/files/Joni-Rutter_900x1000px.jpeg | Joni Rutter Shares Goals and Next Steps for NCATS’ Strategic Plan | Joni Rutter shares her goals for NCATS’ next strategic plan and ways the translational science community can co-build it. | /sites/default/files/Joni-Rutter_900x1000px_0.jpeg | Joni Rutter Shares Goals and Next Steps for NCATS’ Strategic Plan | ||
| 288 | Biomimetic Actinide Decorporation Agents: Enabling Availability | Historically, contamination due to radioactive materials has generally been limited to small numbers of radiation workers in controlled situations, with appropriate expertise available for diagnosis and treatment. Medical management of individuals with internal radiological contamination focuses on removing the radioactive material from the body, a process called radionuclide decorporation. Strategies for decorporation are fairly simple; for example, one method is binding the radionuclide so the body cannot absorb it and it can be passed out through the colon. In today’s world, a terrorist event such as a so-called “dirty bomb” could contaminate hundreds in a single incident. Effective decorporation agents would be needed quickly and in large quantities. These researchers are developing two agents that can bind plutonium so it is unavailable for absorption by the body. These agents are up to 30 times more active than any currently in use for this purpose. Scientific Synopsis Therapy for radioisotope contamination of a large population by a dirty bomb or other event will require a cocktail of decorporation agents because of the wide variety of possible radionuclides and their chemical/biological properties. Decorporation is the only way to reduce exposure of certain incorporated radioisotopes. Fission product lanthanides and the actinides are among the most intractable of these elements to decorporate. While diethylenetriaminepentaacetic acid (DTPA) has been the standard therapy for actinide/lanthanide decorporation since its development and use by the U.S. Atomic Energy Commission in the 1950s, it is limited in efficacy. A new family of sequestering agents has been developed using a biomimetic design based on the similar biochemical transport properties of plutonium(IV) and iron(III). These agents are more selective and have higher affinity for plutonium(IV) and a number of other actinide metal ions. Extensive toxicity and efficacy studies using a mouse model have been published, and limited tests have been done in dogs and baboons. The results established that several of the new agents are up to 30 times more effective than DTPA and, unlike DTPA, can be orally active. Under a currently funded NIAID Bioshield project, we have conducted additional studies with two lead compounds, 3,4,3-LI-1,2-HOPO (an octadentate ligand) and 5-LIO-Me-3,2-HOPO (a tetradentate ligand), with the intention of moving these two ligands toward clinical use by scaling up the synthesis, establishing preparation methods suitable for good manufacturing practice (GMP), carrying out limited efficacy and toxicity studies for combinations of the two chelators in a mouse model, completing toxicity studies in human cell lines, and establishing preclinical safety of the candidate ligands under good laboratory practice (GLP) guidelines. This has been accomplished by an effective partnering of the Actinide Chemistry Group of Lawrence Berkeley National Laboratory (LBNL), which has expertise in ligand design, synthesis and laboratory testing, with SRI International, which has expertise in GLP testing and bringing pharmaceutical products to market. The objective of this application is to enable the availability of multi-kilogram amounts of these two new decorporation agents so that test compound availability does not become a bottleneck in studies leading to clinical availability. This will be work in tandem with the NIAID Bioshield program to develop a pre–Investigational New Drug (IND) stage to obtain FDA input in our development plan, followed by additional pivotal testing necessary for the successful filing of a full IND application. Lead Collaborators University of California, Berkeley Kenneth N. Raymond, Ph.D. Eleanor Blakely, Ph.D. Polly Chang, Ph.D. Patricia Durbin, Ph.D. David Shuh, Ph.D. Public Health Impact Therapy for radioisotope contamination of a large population by a dirty bomb or other event will require a cocktail of decorporation agents because of the wide variety of possible radionuclides and their chemical/biological properties. The new family of sequestering agents produced in the Berkeley program are more selective and have higher affinity for plutonium(IV) and a number of other actinide metal ions than diethylenetriaminepentaacetic, which has been the standard therapy for actinide/lanthanide decorporation for the last 60 years. Outcomes Work on this project is complete. Additional preclinical development was supported by the National Institute of Allergy and Infectious Diseases’ Radiation and Nuclear Countermeasures Program. The investigator successfully filed an IND application using BrIDGs data and material. Project Details Synthesis of Good Manufacturing Practice (GMP) material | ||||||||
| 287 | Authorization | NCATS was created on Dec. 23, 2011, by the Consolidated Appropriations Act, 2012, (P.L. 112-74), which amended the Public Health Service (PHS) Act by including authorization language for NCATS. The 21st Century Cures Act (P.L. 114-255), which became law on Dec. 13, 2016, subsequently modified NCATS' authorization language. The current PHS Act authorization language for NCATS (PDF - 133KB) includes the purpose of NCATS, the phases of clinical trials that may be supported, the NCATS biennial report, and the previously existing NIH programs that were moved to NCATS, such as the Cures Acceleration Network. Cures Acceleration Network (CAN) CAN was established within NIH on March 23, 2010, by the Patient Protection and Affordable Care Act (P.L. 111-148), but it was not appropriated any funds. Several stakeholders wrote a letter to Congress (PDF - 35KB) on May 14, 2010, asking Congress to provide funding for CAN. On Dec. 23, 2011, the Consolidated Appropriations Act, 2012, appropriated $10 million for CAN and moved CAN to NCATS. The purpose of CAN is to award grants and contracts to eligible entities to accelerate the development of high-need cures, including through the development of medical products and behavioral therapies. Congressional Committees The following committees oversee NIH, including NCATS, and may hold hearings or introduce legislation affecting NIH. House Energy and Commerce Subcommittee on Health June 21, 2012 – Hearing titled “The NIH — A Review of Its Reforms, Priorities, and Progress” The purpose of the hearing was to review the implementation of the 2006 NIH Reform Act, the progress of the National Center for Advancing Translational Sciences, and the determination of NIH funding and research priorities. See the background memo (PDF - 115KB). Francis S. Collins, M.D., Ph.D., NIH director, was the only witness. Read his opening statement (PDF - 159KB). Visit the hearing website, which includes a video of the hearing. Senate Committee on Health, Education, Labor, and Pension April 28, 2015 – Hearing titled “Continuing America’s Leadership: The Future of Medical Innovation for Patients” Christopher P. Austin, M.D., NCATS director, testified along with Roderick I. Pettigrew, Ph.D., M.D., director of the National Institute of Biomedical Imaging and Bioengineering, and two directors from the Food and Drug Administration. Read Austin's opening statement (PDF - 150KB). Visit the hearing website, which includes a video of the hearing. | ||||||||
| 286 | Alternative Formulations of Decitabine to Reactivate Fetal Hemoglobin Production | Sickle cell disease (SCD) is a blood disorder that is passed down through families. About 70,000 Americans and millions around the world are affected by the condition. Red blood cells carry a protein called hemoglobin, which transports oxygen from the lungs to the rest of the body. People with SCD have an abnormal form of hemoglobin that causes red blood cells to become crescent (or sickle) shaped instead of being round. A gene necessary to produce a type of hemoglobin called fetal hemoglobin is turned off. Because of this irregular shape, sickle cells cannot move through blood vessels easily, and they slow blood flow to limbs and organs. This blockage causes pain and organ damage, and it can lead to infection. Fetal hemoglobin is thought to prevent cells from becoming sickle-shaped and blocking blood flow. Currently, no widely available cure exists for SCD. The investigators are developing a drug that can turn the fetal hemoglobin gene back on, allowing the body to produce this type of hemoglobin again. The drug could become a new treatment for SCD. Scientific Synopsis SCD (a β-globinopathy) results from the homozygous inheritance of an abnormal β-globin gene. The γ-globin gene is necessary for fetal hemoglobin (HbF) production; this gene is silenced during the latter stages of fetal development concurrent with activation of the β-globin gene. A number of scientific, epidemiologic and clinical observations have indicated that increased levels of HbF improve the natural history of SCD and other β-globinopathies by substituting for, or interfering with, the abnormal β-globin gene product. Therefore, a major translational and clinical objective in the preceding 30 years has been to develop effective pharmacologic reversing agents of γ-globin gene silencing. One result of these efforts is the use of hydroxyurea in SCD. However, hydroxyurea only has limited efficacy. A large body of preclinical and clinical evidence indicates that the non-patented cytidine analogue decitabine could be a more effective reactivator of HbF production. Supply, appropriate formulation and toxicology studies of decitabine through BrIDGs will allow important trials in SCD and β-thalassemia to proceed. Lead Collaborator Cleveland Clinic Yogen Saunthararajah, M.D. Public Health Impact Clinical and epidemiologic observations supported by laboratory studies demonstrating the ability of HbF to interfere with sickle hemoglobin polymerization and prevent sickling — and our understanding of SCD pathophysiology — indicate that effective HbF reactivation remains a worthwhile strategy to treat SCD. Decitabine offers the possibility of even greater and more widespread benefit than the current standard of care, possibly with a similar or better toxicity profile. Outcomes The investigator successfully filed an Investigational New Drug (IND) application to the Food and Drug Administration using BrIDGs data and initiated clinical testing. Project Details Synthesis of Good Manufacturing Practice (GMP) material Pharmacokinetic/absorption, distribution, metabolism, and excretion (PK/ADME) studies IND-directed toxicology Publications Subchronic Oral Toxicity Study of Decitabine in Combination with Tetrahydrouridine in CD-1 Mice • International Journal of Toxicology • Mar. 17, 2014 Increased CDA Expression/Activity in Males Contributes to Decreased Cytidine Analog Half-Life and Likely Contributes to Worse Outcomes with 5-azacytidine or Decitabine Therapy • Clinical Cancer Research • Feb. 15, 2013 Effects of Tetrahydrouridine on Pharmacokinetics and Pharmacodynamics of Oral Decitabine • Blood • Feb. 2, 2012 | ||||||||
| 284 | Advanced Studies with 5HMF—Most Potent Anti-Sickling Agent | Sickle cell disease is an inherited condition with several forms, all caused by mutations in the HBB gene and all affecting hemoglobin, the protein in red blood cells that carries oxygen. Symptoms are caused by “sickling” of the red blood cells, which means the cells are distorted into a sickle or crescent shape. The disease usually begins in childhood, and its symptoms include a low number of red blood cells, repeated infections and periodic pain. The most common form is called sickle cell anemia. Sickle cell disease affects approximately 100,000 Americans and occurs primarily in people of African or Mediterranean heritage. The only currently used treatment has serious side effects and does not work for some patients. These researchers are developing a new anti-sickling agent that works by binding with the defective hemoglobin that causes sickling. Scientific Synopsis Sickle cell disease is a hereditary blood disorder, affecting millions of patients worldwide. The disease occurs in about 1 in every 600 African-American births and 1 in every 1,000–1,400 Hispanic-American births. About 2 million Americans carry the sickle cell trait. Currently, cytotoxic hydroxyurea is the only FDA-approved drug that is being used clinically. However, hydroxyurea therapy is associated with various undesirable side effects, and not all patients benefit from this treatment. Despite considerable effort, there has been little progress in the development of new antisickling agents that have efficacy and safety in vivo. In collaboration with the NHLBI Sickle Cell Disease Reference Laboratory, we have discovered a new potent and specific antisickling 5-membered aromatic scaffold, 5HMF. Results indicate that 5HMF possesses all unique properties of a potential drug candidate and clearly warrants a further preclinical evaluation. Lead Collaborator Virginia Commonwealth University, Richmond Donald J. Abraham, Ph.D. Public Health Impact Since sickle cell disease is an orphan disease, only a few companies are interested and are involved in sickle cell research. One of the major challenges in finding effective therapeutic agents for the treatment of sickle cell disease has been the lack of agents that would specifically bind with the high concentration of intracellular HbS present in patients without causing adverse effects, and 5HMF appears to have promise in satisfying this condition. Outcomes After the completion of approved studies, the Therapeutics for Rare and Neglected Diseases program adopted the project for further development. Less than a year after signing the collaborative agreement with Dr. Abraham’s licensing partner, AesRx, TRND completed the preclinical toxicology, chemistry, manufacturing, controls and regulatory studies necessary to support an Investigational New Drug (IND) application to the FDA, and the IND was filed. Upon clearance from the FDA, 5HMF, under the new name Aes-103, was moved into Phase I clinical trials in both healthy volunteers and sickle cell disease patients. TRND established a project team that includes TRND staff; AesRx staff; and a leading sickle cell disease clinical researcher at NIH’s National Heart, Lung, and Blood Institute. After adoption of the project into the TRND portfolio, AesRx obtained a Massachusetts Life Sciences Center Accelerator Loan to support additional studies needed to complete clinical development of Aes-103. In July 2014, the biopharmaceutical company Baxter International acquired Aes-103 for further clinical development — the first time a company has acquired a drug candidate developed in part by TRND researchers. Project Details Synthesis of Good Manufacturing Practice (GMP) and non-GMP material Formulation development Publications 5-hydroxymethyl-2-furfural Modifies Intracellular Sickle Haemoglobin and Inhibits Sickling of Red Blood Cells • British Journal of Haematology • February 2005 Structural Basis for the Potent Antisickling Effect of a Novel Class of Five-Membered Heterocyclic Aldehydic Compounds • Journal of Medicinal Chemistry • Sept. 9, 2004 | ||||||||
| 283 | Past Budgets | Information about previous fiscal year (FY) budgets for NCATS is available below. Fiscal Year 2022 Fiscal Year 2021 Fiscal Year 2020 Fiscal Year 2019 Fiscal Year 2018 Fiscal Year 2017 Fiscal Year 2016 Fiscal Year 2015 Fiscal Year 2014 Fiscal Year 2013 Fiscal Year 2012 Fiscal Year 2022 Appropriation Law On March 15, 2022, the President signed into law (P.L. 117-103) the “Consolidated Appropriations Act, 2022.” The Act provides the following for NCATS: National Center for Advancing Translational Sciences For carrying out section 301 and title IV of the PHS Act with respect to translational sciences, $882,265,000: Provided, That up to $60,000,000 shall be available to implement section 480 of the PHS Act, relating to the Cures Acceleration Network: Provided further, That at least $606,646,000 is provided to the Clinical and Translational Sciences Awards Program. Budget Request On May 28, 2021, the President’s Budget for FY 2022 was released. The FY 2022 budget request for NIH is $51,957.7 million. The FY 2022 budget request for NCATS (PDF - 1.9MB) is $879.0 million. A 2-page NCATS fact sheet (PDF - 388KB) is also available. Click to view/download Congressional Justification FY 2022 Click to view/download fact sheet Fiscal Year 2021 Appropriation Law On Dec. 27, 2020, the President signed into law (P.L. 116-260) the “Consolidated Appropriations Act, 2021.” The Act provides the following for NCATS: National Center for Advancing Translational Sciences For carrying out section 301 and title IV of the PHS Act with respect to translational sciences, $855,421,000: Provided, That up to $60,000,000 shall be available to implement section 480 of the PHS Act, relating to the Cures Acceleration Network: Provided further, That at least $586,841,000 is provided to the Clinical and Translational Sciences Awards Program. Budget Request On Feb. 10, 2020, the President’s Budget for FY 2021 was released. The FY 2021 budget request for NIH is $38,694,000,000. The FY 2021 budget request for NCATS (PDF - 830KB) is $787,703,000. Fiscal Year 2020 Appropriation Law On Dec. 20, 2019, the President signed into law (P.L. 116-94) the “FY 2020 Further Consolidated Appropriations Act, 2020.” The Act provides the following for NCATS: National Center for Advancing Translational Sciences For carrying out section 301 and title IV of the PHS Act with respect to translational sciences, $832,888,000: Provided, That up to $60,000,000 shall be available to implement section 480 of the PHS Act, relating to the Cures Acceleration Network: Provided further, That at least $578,141,000 is provided to the Clinical and Translational Sciences Awards Program. Congressional Appropriations Hearings The Congressional Appropriations Subcommittees on Labor, Health and Human Services, Education, and Related Agencies held hearings on the NIH budget request: House Hearing: Sept.25, 2019 Subcommittee Website Hearing Website Title: Investments in Medical Research at Five Institutes and Centers of the National Institutes of Health NCATS Director’s Statement for the Record (PDF - 333KB) Senate Hearing: April 11, 2019 Subcommittee Website Hearing Website Title: Review of the FY2020 Budget Request for NIH House Hearing: April 2, 2019 Subcommittee Website Hearing Website Title: National Institutes of Health Budget Request for FY 2020 Budget Request On March 18, 2019, the full President’s Budget for FY 2020 was released. The FY 2020 budget request for NIH is $34,367,629,000. The FY 2020 budget request for NCATS (PDF - 656KB) is $694,112,000. On March 11, 2019, an overview of the President’s Budget for FY 2020, A Budget for a Better America (PDF - 1.9MB), was released. NIH is described on page 46 under “Prioritizes Critical Health Research.” On the same day, HHS Secretary Azar released a statement on President Trump’s FY 2020 Budget. HHS also released an HHS Budget in Brief (PDF - 7MB), which describes NIH on pages 52-59. Fiscal Year 2019 Appropriation Law On Sept. 28, 2018, the President signed into law (P.L. 115-245), the Department of Defense and Labor, Health and Human Services, and Education Act, 2019 and Continuing Appropriations Act, 2019, funding NIH/NCATS for the full fiscal year. The Act provides the following for NCATS: National Center for Advancing Translational Sciences For carrying out section 301 and title IV of the PHS Act with respect to translational sciences, $806,373,000: Provided, That up to $80,000,000 shall be available to implement section 480 of the PHS Act, relating to the Cures Acceleration Network: Provided further, That at least $559,736,000 is provided to the Clinical and Translational Sciences Awards Program. Congressional Appropriations Hearings The Congressional Appropriations Subcommittees on Labor, Health and Human Services, Education, and Related Agencies usually hold hearings on the NIH budget request. Senate Hearing: May 17, 2018 Subcommittee Website • NCATS Director's Statement for the Record (PDF - 28KB) House Hearing: April 11, 2018 Subcommittee Website Budget Request The President released his FY 2019 budget on Feb. 12, 2018. The FY 2019 budget request for NCATS (PDF - 436KB) is $685,087,000. NIH is described on pages 40-46 of the HHS Budget-in-Brief (PDF - 1.9MB). Fiscal Year 2018 Appropriation Law On March 23, 2018, the President signed into law (P.L. 115-141), the Consolidated Appropriations Act, 2018 (also known as the Omnibus), funding NIH/NCATS through the end of the fiscal year. The Act provides the following for NCATS: National Center for Advancing Translational Sciences For carrying out section 301 and title IV of the PHS Act with respect to translational sciences, $742,354,000: Provided, That up to $25,835,000 shall be available to implement section 480 of the PHS Act, relating to the Cures Acceleration Network: Provided further, That at least $542,771,000 is provided to the Clinical and Translational Sciences Awards program. The Explanatory Statement accompanying the Act includes the following: Clinical and Translational Science Awards (CTSA) Program.—The bill provides $542,771,000, an increase of $26,651,000, for the CTSA program. The agreement continues to support the program, a stabilization in the number of hubs funded, and a five year grant cycle. The agreement acknowledges the positive changes made to the program in response to language included in the fiscal year 2018 Senate Report, including the increase in communication and collaboration with the Committees on Appropriations of the House of Representatives and the Senate. The agreement expects the Director to provide quarterly updates to principal investigators of CTSA hubs beginning within 30 days of enactment of this Act and to continue the ongoing updates to the Committees. Finally, the agreement expects written notification to continue to be provided to the Committees at least three days in advance of any public release of CTSA grant awards. Continuing Resolutions Per Public Law 115-56 (Continuing Appropriations Act, 2018), as amended by Public Law 115-90 (Further Continuing Appropriations Act, 2018), Public Law 115-96 (Further Additional Continuing Appropriations Act, 2018), Public Law 115-120 (Extension of Continuing Appropriations Act, 2018), and Public Law 115-123 (Further Extension of Continuing Appropriations Act, 2018), the federal government operated under a Continuing Resolution through March 23, 2018. Budget Request The President released his FY 2018 budget on May 23, 2017. The FY 2018 budget request for NCATS (PDF - 563KB) is $557,373,000. Fiscal Year 2017 Appropriation Law On May 5, 2017, the President signed into law (P.L. 115-31), the Consolidated Appropriations Act, 2017, funding NIH/NCATS through the end of the fiscal year. The law provides the following for NCATS: National Center for Advancing Translational Sciences For carrying out section 301 and title IV of the Public Health Services (PHS Act) with respect to translational sciences, $705,903,000: Provided, That up to $25,835,000 shall be available to implement section 480 of the PHS Act, relating to the Cures Acceleration Network: Provided further, That at least $516,120,000 is provided to the Clinical and Translational Sciences Awards program. Congressional Appropriations Hearings The Congressional Appropriations Subcommittees on Labor, Health and Human Services, Education, and Related Agencies usually hold hearings on the NIH budget request. Senate Hearing: April 7, 2016 Subcommittee Website • Archived Webcast • NCATS Director's Statement for the Record (PDF - 24KB) House Hearing: March 16, 2016 Subcommittee Website Budget Request The President released his FY 2017 budget on Tuesday, Feb. 9, 2016. The FY 2017 budget request for NCATS (PDF - 402KB) is $685.417 million, which is the same as the FY 2016 enacted level. Fiscal Year: 2016 Appropriation Law On Dec. 18, 2015, the President signed into law the Consolidated Appropriations Act, 2016, funding NIH/NCATS through the end of the FY. The law (H.R. 2029) provides the following for NCATS: National Center for Advancing Translational Science For carrying out section 301 and title IV of the PHS Act with respect to translational sciences, $685,417,000: Provided, That up to $25,835,000 shall be available to implement section 480 of the PHS Act, relating to the Cures Acceleration Network: Provided further, That at least $500,000,000 is provided to the Clinical and Translational Sciences Awards program. Congressional Appropriations Hearings The Congressional Appropriations Subcommittees on Labor, Health and Human Services, Education, and Related Agencies usually hold hearings on the NIH budget request. Senate Hearing: April 30, 2015 Subcommittee Website • Archived Webcast • NCATS Director's Statement for the Record (PDF - 70KB) House Hearing: March 3, 2015 Subcommittee Website Budget Request The President released his FY 2016 budget on Monday, Feb. 2, 2015. The FY 2016 budget request for NCATS (PDF - 418KB) is $660.131 million, an increase of $27.421 million over the FY 2015 enacted level. Fiscal Year: 2015 Appropriation Law On Dec. 16, 2014, the President signed an appropriations bill (the “CRomnibus”) into law that funds NIH/NCATS through the end of the FY. The law (P.L. 113-235) provides the following for NCATS: “For carrying out section 301 and title IV of the PHS Act with respect to translational sciences, $635,230,000: Provided, That up to $9,835,000 shall be available to implement section 480 of the PHS Act, relating to the Cures Acceleration Network: Provided further, That at least $474,746,000 is provided to the Clinical and Translational Sciences Awards program.” Congressional Appropriations Hearings The Congressional Appropriations Subcommittees on Labor, Health and Human Services, Education, and Related Agencies usually hold hearings on the NIH budget request. Senate Hearing: April 2, 2014 Subcommittee Website • Archived Webcast • NCATS Director's Statement for the Record (PDF - 178KB) NCATS Director Christopher P. Austin, M.D., attended this hearing. House Hearing: March 26, 2014 Subcommittee Website Budget Request The President released his FY 2015 budget on Tuesday, March 4, 2014. The FY 2015 budget request for NCATS (PDF - 539KB) is $657.471 million, an increase of $25.075 million over the FY 2014 enacted level. Requested changes reflect funding for new initiatives; additional competing research project grants over FY 2014; Small Business Innovation Research/Small Business Technology Transfer awards; expanded NCATS collaboration with the NIH Clinical Center; and redirected AIDS research funds to expand NIH support for research directed toward a cure for HIV. Fiscal Year: 2014 Appropriation Law On Jan. 17, 2014, Congress passed and the President signed an appropriations bill that funds NIH/NCATS through the end of the FY. The law (P.L. 113-76) provides the following for NCATS: "For carrying out section 301 and title IV of the PHS Act with respect to translational sciences, $633,267,000: Provided, That up to $9,835,000 shall be available to implement section 480 of the PHS Act, relating to the Cures Acceleration Network: Provided further, That at least $474,746,000 is provided to the Clinical and Translational Sciences Awards program." Budget Request The President released his FY 2014 budget on Wednesday, April 10, 2013. The FY 2014 budget request for NIH was $31.3 billion. The FY 2014 budget request for NCATS (PDF - 835KB) was $665.688 million, an increase of $91.391 million over the FY 2012 level. Specific increases were requested for the Cures Acceleration Network (+$40.111 million); Clinical and Translational Science Awards (+$1.108 million); the Therapeutics for Rare and Neglected Diseases program (+$3.79 million); and Small Business Innovation Research/Small Business Technology Transfer program (+$3.4 million). Requested increases reflect the beginning of direct funding (+$31.34 million) by NCATS of the Bridging Interventional Development Gaps program, the NCATS Chemical Genomics Center, the BioAssay Research Database, and the Small Molecule Repository, which were previously supported by the NIH Common Fund. In addition, there was a requested increase for Translational Research Resources (+$10.704 million) to provide for NCATS’ increased share of trans-NIH programs and initiatives that support the entire spectrum of biomedical research. Fiscal Year 2013 Appropriation Law On Sept. 28, 2012, the President signed into law the Continuing Appropriations Resolution, 2013 (P.L. 112-175 [PDF - 136KB]). In absence of an appropriation law, this Continuing Resolution (CR) funded the federal government through March 27, 2013, at levels provided in FY 2012. To meet the bipartisan agreement between the House, Senate and White House that ensured a total rate of government operations at $1.047 trillion, a government-wide, across-the-board increase of 0.612 percent over the base rate also was included in the CR. Budget Request The President released his FY 2013 budget request on Monday, Feb. 13, 2012. The FY 2013 budget request for NIH was $30.9 billion, the same as the FY 2012 level. This level demonstrated the Administration’s commitment to placing a priority on investing in innovative biomedical and behavioral research to advance medical science. NCATS was a priority of the NIH Director, with an additional $64.32 million provided over FY 2012. The FY 2013 budget request for NCATS (PDF - 783KB) was $639.033 million, an increase of $64.32 million over the FY 2012 level. Specific increases were provided for the Cures Acceleration Network (+$39.63 million); direct funding of the NCATS Chemical Genomics Center (+$13 million), Clinical and Translational Science Awards (+$1.11 million), and small increases for mandatory costs such as Small Business Innovative Awards and NCATS share of shared resources. Fiscal Year 2012 Appropriation Law NCATS received its first appropriation (funding) in the Consolidated Appropriations Act, FY 2012 (P.L. 112-74) on Dec. 23, 2011: NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES For carrying out section 301 and title IV of the PHS Act with respect to translational sciences, $576,456,000: Provided, That up to $10,000,000 shall be available to implement section 402C of the PHS Act, relating to the Cures Acceleration Network: Provided further, That funds appropriated may be used to support the reorganization and activities required to eliminate the National Center for Research Resources: Provided further, That the Director of the NIH shall ensure that, of all funds made available to Institute, Center, and Office of the Director accounts within ‘‘Department of Health and Human Services, National Institutes of Health,’’ at least $487,767,000 is provided to the Clinical and Translational Sciences Awards program. After an across the board rescission, the FY 2012 appropriation for NCATS is $574,713,000, plus funding provided by the NIH Common Fund and other sources. Budget Request In June 2011, the Department of Health and Human Services sent detailed budget information for the proposed NCATS, titled Restructuring the National Institutes of Health to Advance Translational Science, to appropriators in the House and Senate. | ||||||||
| 282 | A Novel Drug Candidate for the Treatment of Diabetic Retinopathy | The condition called diabetic retinopathy stems from damage to the blood vessels of the retina caused by diabetes. This is the most common diabetic eye disease and a leading cause of blindness in the United States. No treatment is available in the early stages of the disease, which also frequently have no symptoms. Once the disease is discovered, patients can prevent its progression by controlling their blood pressure and their blood sugar and blood cholesterol levels. In the advanced stage called proliferative retinopathy, treatment consists of laser surgery to shrink the abnormal blood vessels. This surgery is not always effective and can destroy normal retinal tissue. No approved pharmaceutical therapy is available. These researchers are developing a new drug candidate with the potential to have sustained effectiveness against the blood leakage into the retina associated with this condition. Scientific Synopsis Diabetic retinopathy (DR) is a common complication of diabetes. Diabetic macular edema (DME) is a major pathological feature of DR and a leading cause of blindness. Cystoid macular edema (CME) represents a common cause of vision impairment following cataract surgery. High blood-retinal barrier or retinal vascular leakage is believed to be responsible for DME and CME. Laser photocoagulation has remained the gold standard for the treatment of DME/CME over the past two decades. However, laser therapy is not always effective, may destroy normal retinal tissues and is often accompanied by side effects. Intravitreal steroids and vascular endothelial growth factor (VEGF) inhibitors have been developed for other ocular diseases. Clinical trials have shown that both therapies confer benefit to some patients with DME and CME, but many patients show only a partial response, and the therapies result in side effects. Because there is no FDA-approved drug for DME and CME, the development of effective therapies for these sight-threatening conditions is in demand. Through a high-throughput screen of more than 200 small molecule compounds, we have identified CLT-003 with promising efficacy on DME. CLT-003NP is a promising drug candidate because it has new and multiple targets and can achieve a sustained efficacy on retinal vascular leakage. The ultimate goal of this project is to combine CLT-003 with nanotechnology to develop a new sustained-release drug for DME and CME. Lead Collaborators University of Oklahoma Health Sciences Center, Oklahoma City Jian-xing Ma, M.D., Ph.D. Ying Chen, M.D., Ph.D. Public Health Impact Currently, there is no FDA-approved pharmacotherapy for the treatment of diabetic retinopathy. The goal of this project is to combine nanotechnology and a novel promising small molecule drug candidate to develop a sustained-release drug treatment of diabetic retinopathy. Outcomes Work on this project is complete. Project Details Synthesis of Good Manufacturing Practice (GMP) and non-GMP material Formulation development Pharmacokinetic/absorption, distribution, metabolism, and excretion (PK/ADME) studies Investigational New Drug (IND)-directed toxicology |
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