Showing 19 ideas for tag "models"

Goal 3: Advance Translational Research

Animal Models for Translational Research and Drug Development

There is a need to identify and develop suitable animal models (e.g. larger, non-primate animal models) that faithfully predict the outcomes of new medicines and treatments in heart, lung, blood, and sleep (HLBS) disorders prior to human clinical trials.

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Critical Challenge (CC)

Details on the impact of addressing this CQ or CC

If animal models can faithfully predict the outcomes in human clinical trials of new medicines and treatments, it will reduce the economic burden for the failure of drug development.

Feasibility and challenges of addressing this CQ or CC

Identification of current available animal models;
Development of new animal models with recent advances in mammalian genome projects and gene targeting technologies could be done over the next 5-10 years
Medical research, especially in basic discovery, has benefited significantly from the use of various animal models, such as gene-targeted and transgenic mouse models. However, many discoveries from animal models (e.g. mouse models) failed to translate into human applications.

Name of idea submitter and other team members who worked on this idea NHLBI Staff

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Goal 3: Advance Translational Research

Enhancing Translational Returns With Better Animal Models and the Basic Science Needed to Support Such Efforts

Can we improve on the preclinical development of therapies through more informed choices on new animal models by linking basic science at the R01 level with national resource centers?

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Critical Challenge (CC)

Details on the impact of addressing this CQ or CC

The development of effective therapies for heart, lung, and blood require the appropriate animal models for testing. Mouse models have been the mainstay and for the most part very effective. But for those diseases where mice fall short, humans have become the testing ground. With the massive push for translation at NIH, clinical trials often lack proof of efficacy in animal models or are wrongly based on biology in rodents that does not apply to humans. These clinical efforts that don’t effectively translate are exhausting resources to maintain a robust RO1 pipeline on basic research. Recognizing that we must push for translation and also keep basic research funded at a high level, NIH and NHBLI needs to get more creative in taping the best animal models for the disease.

Feasibility and challenges of addressing this CQ or CC

With new technologies rapidly expanding for transgenesis in embryos, picking the appropriate species for modeling a given disease is now becoming a reality. However, there are several barriers to growth in this area: 1) we often do not know organ physiology and stem cell biology well enough in non-rodent species, 2) the average researcher typically does not have the expertise to utilize non-rodent models in their research or to generate new genetic non-rodent models for study, 3) the costs of non-rodent disease models is high and must be strategically utilized. One potential solution is to maintain resource centers in particular key species that collaborate with basic scientists to both better understand non-rodent organ biology and work selectively to translate basic discovery into therapies. NHLBI recently had an RFA for this type of work that was discontinued. If a new RFA was designed that links funded research (and/or new research applications) through NHLBI to selected target mission diseases and the use of strategic resource centers with expertise in alternative non-rodent models, this might productively transition appropriate use of new models for the next generation of scientists. Such an RFA for example, could provide supplements to existing R01s for projects linked to resource centers and/or have specific R01 RFAs to enter into studies in new animal models or to create new models for a given purpose.

Name of idea submitter and other team members who worked on this idea John Engelhardt

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48 up votes
17 down votes
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Goal 3: Advance Translational Research

Facilitating the translation of discovery science into proof of concepts in preclinical models

What steps can the research community take to facilitate the translation of discovery science into proof of concepts in preclinical models and in humans for diagnosis, prevention, and treatment?

• Current regulatory environment
• Lack of communication between discovery and clinical research worlds
• Lack of training
• Getting industry, academia, and NHLBI to partner; and the business model to make it happen.
• Limited... more »

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Compelling Question (CQ)

Details on the impact of addressing this CQ or CC

• Increased number of novel therapeutics, diagnostics and devices in early phase clinical trials
• Increased impact in rare diseases and unmet needs
• Increased number of licensed IPs from academic centers

Name of idea submitter and other team members who worked on this idea NHLBI Staff

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17 net votes
25 up votes
8 down votes
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Goal 3: Advance Translational Research

Animal Models for COPD -- Core Facilities

COPD is a major health problem with more than 140,000 deaths per year and yet there is a relative paucity of treatments that might modify the course of this disease. In part, this is due to the poor efficiency of animal models that require months of exposure to cigarette smoke. Moreover, there are no well validated small animal models of chronic mucus hypersecretion. Funding of core facilities that could both provide... more »

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Critical Challenge (CC)

Details on the impact of addressing this CQ or CC

Funding of core facilities that could both provide support for researchers wishing to study COPD, and the development of efficient research models as well as models of chronic bronchitis would be a major advance for screening for treatments of COPD.

Feasibility and challenges of addressing this CQ or CC

Current technology is well established for exposure of small animals to combustible tobacco smoker. However there remains to be developed standardized exposures to e-Cigarettes and Biomass fuels.

Name of idea submitter and other team members who worked on this idea Robert A. Wise

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24 up votes
4 down votes
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Goal 3: Advance Translational Research

The Investigator's Catch-22: How Can NHLBI Help?

The Critical Challenge is to determine how NHLBI can continue to foster the translational research necessary to allow our researchers to further develop their NHLBI-funded basic science discoveries. Researchers can't readily get a "typical" grant to perform the preclinical and early clinical translational IND-enabling research, and also can't yet attract private sector support without having done the work to "de-risk"... more »

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Critical Challenge (CC)

Details on the impact of addressing this CQ or CC

Ensuring that NHLBI-funded researchers have the means to further develop promising research discoveries will ensure that NHLBI continues to fulfill its Mission. Providing funding or resources to move basic science discoveries from the lab towards the clinic can expand the research environments, opportunities, and collaborations available to NHLBI investigators and lead to potential new therapies for heart, lung, and blood diseases.

Feasibility and challenges of addressing this CQ or CC

Just as research project itself can take years, if not decades, to accomplish, so too can a cultural shift in our extramural research community. While one may have a different understanding of what constitutes "translational" research depending upon his or her vantage point, in reality it is bi-directional (from bench to bedside and back to bench) and offers possibilities for a wide range of researchers. Engaging established basic scientists in translational research can open new opportunities to them, and younger researchers are likely more familiar and well-poised for new research paradigms and collaborative efforts such as those afforded by the translational development process.
Basic discovery science is appropriately the backbone of the NHLBI extramural research program. But, for any basic science discovery to have a meaningful impact on human health, it must be "translated from the bench to the bedside." These next steps in translation involve a tremendous amount of research that is not amenable to hypothesis-driven grant mechanisms like an R01 or P01. Without access to funding support for early-stage translational work, investigators can be stymied and NHLBI-funded basic science discoveries can languish.

Name of idea submitter and other team members who worked on this idea NHLBI Staff

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10 net votes
21 up votes
11 down votes
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Goal 3: Advance Translational Research

Developing animal models of lung transplantation.

Lung transplantation as a cure for terminal lung disease has seen little improvement in outcomes for more than 20 years. The field remains highly challenging, in part, because of an absence of robust animal models which are technically- feasible and reproducible across centers. Further, models have limited relevance to clinical (chronic) airway remodeling, the leading problem in pulmonary allografts. In the absence of... more »

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Critical Challenge (CC)

Details on the impact of addressing this CQ or CC

The critical challenge is to address the leading problems facing lung transplant patients through the creative application of multiple technological platforms employing all available pre-clinical models by multiple NIH investigators. With greater focus on the deeper development of existent models, the delineation of their strengths and limitations and importantly, cooperation between Academic Centers, efforts can be optimized to improve outcomes for a condition that has enjoyed little benefit from basic research.

Feasibility and challenges of addressing this CQ or CC

The siloed nature of much clinical and experimental lung transplantation research limits progress and broader initiatives. With specific respect to developing animal models of lung transplantation, the general lack of consensus about the suitability of the techniques employed at different institutions stifles progress. A strategic vision, guided by leaders across the field, highlighting benefits and limitations of current animal models can be coupled with a consensus statement about the most pressing issues in lung transplantation worthy of increased investigation.

Name of idea submitter and other team members who worked on this idea Mark Nicolls

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15 up votes
10 down votes
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Goal 3: Advance Translational Research

Molecular determinants of vascular wall development and aneurysm formation that can be used as markers for early diagnosis

To increase the potential of translating basic research discoveries into the clinic, there is a need to discover molecular biomarkers that confer risk for aneurysms and vascular dissections. The creation of a nation-wide biorepository of well-defined tissue and plasma samples along with research utilizing these tissue samples employing state-of-the art proteomics, genomics and development of appropriate mouse models will... more »

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Critical Challenge (CC)

Details on the impact of addressing this CQ or CC

The challenge is the coordination of all components of the Project (i.e. development of a national biorepository along with coordination of proteomics and genomics analysis as well as proof of concept in animal models).

Feasibility and challenges of addressing this CQ or CC

This process is not feasible via the R01 funding mechanisms. The feasibility of addressing this critical challenge is excellent provided adequate resources are provided.

Name of idea submitter and other team members who worked on this idea Dudley Strickland and Selen Catania Muratoglu

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5 net votes
7 up votes
2 down votes
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Goal 3: Advance Translational Research

Translation Research Dissemination & Implementation Frameworks

We need to identify and test the proven effective dissemination and implementation frameworks that are relevant to heart, lung, and blood disorders in order to scale up evidence-based interventions in real world settings, ultimately improving health equity among minority populations, including low income minority residents living in public housing.

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Critical Challenge (CC)

Details on the impact of addressing this CQ or CC

• Ability to determine how much of an evidence based intervention can be sustained in real world settings.
• Add utilization of D&I frameworks to researcher’s core competency training skills.
• Promote long term sustainability of evidence based interventions.

Feasibility and challenges of addressing this CQ or CC

• Researchers from the 2014 NIH’s Annual Conference on the Science of Dissemination and Implementation: Transforming Health Systems to Optimize Individual and Population Health presented compelling evidence that dissemination and implementation frameworks are an effective means to scaling up evidence based interventions.

Name of idea submitter and other team members who worked on this idea NHLBI Staff

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4 net votes
13 up votes
9 down votes
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Goal 2: Reduce Human Disease

Biology of the intact alveolar wall – the new frontier in lung research

HOW DO WE STUDY THE BIOLOGY OF THE INTACT ALVEOLAR WALL IN THE CONTEXT OF LUNG DISEASE AND REPAIR?

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Compelling Question (CQ)

Details on the impact of addressing this CQ or CC

SEE UPLOADED FILE

Feasibility and challenges of addressing this CQ or CC

SEE UPLOADED FILE

Name of idea submitter and other team members who worked on this idea JAHAR BHATTACHARYA

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2 up votes
0 down votes
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Goal 2: Reduce Human Disease

Interactions between anticoagulant therapy and antiretroviral drugs

Cardiovascular pathology has become a major problem in the management of the HIV-infected patient during the ART era. A large number of HIV patients will receive anticoagulants drugs for secondary prevention of cardiovascular disease. It is therefore critical to understand the interactions between antiretroviral therapy and anticoagulant therapy to safely treat HIV patients.

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Critical Challenge (CC)

Details on the impact of addressing this CQ or CC

With over 50% of HIV-infected patients in the US anticipated to be > 50 years of age by 2015, the overall risk of CVD will be significantly higher and could become the main challenge for the management of chronic HIV infection. A large number of HIV-infected patients with CVD will therefore need treatment for primary and secondary prevention of atherothrombotic events. The secondary prevention of CVD almost invariably includes prescription of one or multiple anticoagulants drugs. It is therefore conceivable that anticoagulant therapies will be frequently associated with ART for the management of HIV patients, which already developed CVD. The interactions between these therapies are not well studied and are critical for the management of the HIV-infected patients.

Feasibility and challenges of addressing this CQ or CC

Feasibility: 1) retrospective studies on a large number of HIV patients that had cardiovascular events and were treated with antiretroviral drugs; 2) prospective studies comparing different antiretroviral regimens associated with the most current anticoagulant therapy recommended for secondary prevention of CV disease; 3) use of animal models of AIDS for testing new anticoagulants and the interaction with the antiretroviral drugs.

Name of idea submitter and other team members who worked on this idea Ivona Pandrea

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5 up votes
3 down votes
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Goal 3: Advance Translational Research

Animal models of vascular diseases

How can we better model human vascular disease in all its complexity?

­This is key to more effective translation of both diagnostics and therapeutics. Develop improved animal models of vascular diseases including PAD, aneurysm, venous diseases, to facilitate fundamental research and preclinical development.

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Compelling Question (CQ)

Name of idea submitter and other team members who worked on this idea Society for Vascular Surgery

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2 net votes
3 up votes
1 down votes
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Goal 2: Reduce Human Disease

Rare disease therapeutics high throughput screening

Can we develop model systems for the high throughput screening of new and existing agents as possible therapies for rare diseases?

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Compelling Question (CQ)

Name of idea submitter and other team members who worked on this idea NHLBI Staff

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-18 net votes
8 up votes
26 down votes
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Goal 3: Advance Translational Research

Roadblocks to discovery and translation in lymphoma

What are the central infrastructure and research roadblocks that are preventing transformational discoveries in lymphoma

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Critical Challenge (CC)

Details on the impact of addressing this CQ or CC

Outlined in the attached manuscript published by a committee of experts organized by the American Society of Hematology

Name of idea submitter and other team members who worked on this idea David Weinstock for the Steering Committee of the 2014 ASH Meeting on Lymphoma Biology

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Goal 2: Reduce Human Disease

New analysis methods for research using animal models

The idea that 'animal models can faithfully predict the outcomes in human clinical trials of new medicines and treatments' is highly compelling. However, due to differences (biological and non-biological) between humans and animals this goal can likely not be achieved. Not only are animals genetically different from humans, everything else is different too. Even if living quarters are shared (e.g. house pet animals),... more »

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Critical Challenge (CC)

Details on the impact of addressing this CQ or CC

Because of the differences between humans and animals, a different paradigm of expectations and analysis methodology needs to be developed. Animal models (natural and man-made) have been superbly informative for developing means to improving human health. The key to 'successful animal models' is the interpretation of the data - and the careful design of the animal studies to capture one of the essential molecular, environmental, behavioral problems that cause the human disease and to model the essential problem in the animals.

Feasibility and challenges of addressing this CQ or CC

At the moment, the specific design of animal models and the interpretation of the data is in the hands of individual scientists. Specific guidelines could be developed for every aspect of animal experimentation and this would help to optimize the output with respect to understanding the next steps: e.g. is this data useful in basic science, in translational science, which questions need to be answered using the analysis of human individuals ? The availability of specific methods will allow us to better move between bedside to bench and back.

Name of idea submitter and other team members who worked on this idea gg

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7 up votes
19 down votes
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