Showing 8 ideas for tag "animal"

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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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)

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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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Goal 3: Advance Translational Research

NIH should promote, rather than deter “fast-track” translational research projects

In the current environment, NIH reviewers actually deter, rather than promote, progress on proposed pre-clinical animal research that is most likely to rapidly translate into clinical breakthroughs in the short term. Scientists should be allowed to focus on critical missing information (roadblocks) needed to accelerate a promising treatment to clinical trials. For instance, at the NHLBI there is currently no study section... 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

Yes, large animal studies may often be desirable too. But, the comprehensive information needed can be dramatically accelerated by using small rodents (e.g. by increased “n” and shorter lifespan). Then and if necessary, more focused large animal studies can be used more judiciously before commencing human trials. If a proposed, well-designed, translational study has identified a promising new treatment and the PI seeks to collect critical information to set the stage for clinical trials, he/she should be given the chance to conduct this research instead of being directed toward many years of collecting mechanistic data for something that is ready to move toward clinical study. Later, we can prop our feet on the desk and leisurely design those mechanistic studies knowing that more people are surviving, rather than dying. Rome burns while we play!

Feasibility and challenges of addressing this CQ or CC

Can be done now by simply fast-tracking studies that may truly accelerate improvements in patient outcomes. Knowing that is works is more important than how it works from the patient standpoint.

Name of idea submitter and other team members who worked on this idea Anthony Martin Gerdes

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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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Goal 3: Advance Translational Research

The need for funding priorities and emphasis on valve disease and large-animal preclinical studies

Investigators need NHLBI support for programs that transform our approach to heart valve disease to mechanism-based prevention with large-animal preclinical studies through: an NHLBI-sponsored sponsored Heart Valve Network; development of models of genetic and acquired valve disease; a study section devoted to valve disease; and RFAs and RFPs based on Task Force priorities in mitral valve disease.

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

Details on the impact of addressing this CQ or CC

Improved health through mechanism-based prevention in an increasing cause of heart failure. Support for research that can lead directly to clinical applications yet has basic aims.

Feasibility and challenges of addressing this CQ or CC

With NHLBI support, the resources and talented investigators can make this possible.

Name of idea submitter and other team members who worked on this idea Robert A. Levine, MD and member of the Leducq Mitral Network

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Goal 3: Advance Translational Research

Funding for synthesis and screening of potentially therapeutic molecules

Currently, there are limited, if none, funding resources to synthesize and screen potentially therapeutic molecules, based on supportive findings in cells, biopsy tissues from the patients with the disease in question, and the preliminary data to support the development of a series of compounds to screen them for their pharmacokinetics, pharmacodynamics, toxicity and use in clinically-relevant large animal models.

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

Details on the impact of addressing this CQ or CC

Although NHLBI-NIH and other institutes emphasize on mechanistic approach, to my knowledge, translation of the findings into the development of novel molecules is rarely pursued in a multi-disciplinary manner. this could have a significant impact on developing better therapeutic and/or management approaches of various diseases.

Feasibility and challenges of addressing this CQ or CC

In the past, NIH has come up with many RFAs related to this issue. However, one of the major challenges has been the screening of the compounds in a model relevant to human disease. For example, in cardiovascular diseases, about 99% studies are done in mouse models. From genetic studies point of view, this is acceptable, even though now large animals are used for knock-in and knock out gene studies. However, from the screening point of view, an emphasis must be placed on clinically-relevant model, for example, swine, where most of the findings, if not all, could translated to human disease.

Name of idea submitter and other team members who worked on this idea Devendra K. Agrawal, PhD

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Goal 3: Advance Translational Research

Develop relevant large animal models for various disease conditions

What is the possibility of investing funds primarily in clinically-relevant models where the findings could be translated in to human diseases?

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

Details on the impact of addressing this CQ or CC

Strong emphasis on the use of a clinically-relevant large animal model would hopefully be more productive in developing better therapeutic approaches and management of patients.

Feasibility and challenges of addressing this CQ or CC

In view of the lack of facility at many institutions and the cost involved, and the rules and regulations by the USDA and other regularity bodies, special emphasis will be required to build the animal facility at an institution. Where will the funds come from? Similar to many other core facilities set up by the NIH at various institutions, what is the possibility of developing specialized centers for testing a new idea in a clinically-relevant large animal facility?

Name of idea submitter and other team members who worked on this idea Devendra K. Agrawal, PhD

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