Goal 2: Reduce Human Disease

How can the study of rare diseases inform our understanding of common diseases?

How can the study of rare diseases inform our understanding of common diseases?

Submitted by (@nhlbiforumadministrator)

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 : Research Advocacy Committee, American Thoracic Society

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Goal 3: Advance Translational Research

Treating cardiovascular disease in persons with mental health disorders

How can we most effectively prevent and treat cardiovascular disease among persons with serious mental disorders?

Submitted by (@nhlbiforumadministrator)

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

Details on the impact of addressing this CQ or CC :

Clinical anxiety disorders affects 40 million people in the US and the lifetime prevalence of PTSD is 6-8%,. The incidence of PTSD in particular is rapidly expanding in the US; this condition doubles the risk of a cardiac event.

 

The prevalence rates are higher in some populations; 3 out of 10 US military veterans have a diagnosis of PTSD, and many more are undiagnosed. Among patients at a VA, a diagnosis of PTSD increased the probability of circulatory problems (odds ratio 3.7). In another study, every additional PTSD symptom increased the risk of developing cardiovascular disease by 17%. Thus, the impact of developing more effective treatments adapted to the needs of this vulnerable population could be significant.

Feasibility and challenges of addressing this CQ or CC :

As the incidence of many mental health disorders such as PTSD and depression increases, the need for developing and adapting treatments for this population becomes critical.

 

Effective treatments may not be optimal for persons with serious mental illnesses and strategies to tailor treatments to the challenges of this vulnerable population are needed.

Individuals with mental illnesses such as major depressive disorder, bipolar disorder, and anxiety disorders are at significantly higher risk for cardiovascular disease than are those without these illnesses. Those with serious mental illnesses die an average of 25 years earlier, frequently from cardiovascular disease. The incidence of PTSD is rapidly expanding in the US; this condition doubles the risk of cardiovascular events.

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

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Goal 2: Reduce Human Disease

Relevance of cardiovascular disease associated with autoimmunity research

NIH estimates up to 23.5 million Americans suffer from autoimmune disease (AD) and up to 24 million from heart diseases. As a result, NIH and AHA estimates the annual direct health care costs for AD to be in the range of $100 billion and $200 billion for heart and stroke diseases. Yet this area of research has been neglected and underfunded. The proposition is for NHLBI to partner with other NIH institutes dealing with ...more »

Submitted by (@mboutjdir)

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

Details on the impact of addressing this CQ or CC :

Reduce the impact of autoimmune diseases on the heart and vascular system.

Feasibility and challenges of addressing this CQ or CC :

Generate RFAs dedicated to the field of autoimmune associated cardiovascular diseases.

Name of idea submitter and other team members who worked on this idea : M. Boutjdir

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15 up 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.

Submitted by (@societyforvascularsurgery)

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 2: Reduce Human Disease

What about the impact of regulation of genes in response to external stimulation on human health

We are focusing a lot on the genes that may be protective or harmful to our lives. But what about the regulation of genes in response to external stimulations, such as psychosocial and/or environmental, that are probably more accountable for whether we live healthier or not.

Submitted by (@jiang001)

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

Details on the impact of addressing this CQ or CC :

Rationale: Years of research in the mind-heart field have set examples that looking at changes during dynamic stimulations (chronic, acute, and acute superimposed on chronic) are more meaningful for us to better understand how the body truly works. Therefore, research design in mimicking real dynamic process is necessary to truly capture the healthy or harmful phenotypes driven by genotypes. I suggest the NHLBI to establish a platform gathering resources to promote more sophisticated research from basic to clinical to better understand the underlying mechanisms of psychosocial impact on cardiovascular diseases that has come to a sizable problem for the human being in US and world wide.

Feasibility and challenges of addressing this CQ or CC :

We have performed researches that allow us to identify phenotypes that are only appearing under emotional stress testing. Currently we are examining whether certain intervention may modify these kinds of changes. Even our studies fail to demonstrate changes with intervention, the findings support future studies focusing on testing dynamic changes under stress that reflects daily living. Resting data obtained in laboratory does not truly represent what human beings experiences.

Name of idea submitter and other team members who worked on this idea : Wei Jiang from Duke University

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Goal 2: Reduce Human Disease

Immunologic Treatment of Hematologic Malignancies

How can the use of CAR T-cell and checkpoint blockade strategies be optimized in order to cure hematologic diseases?

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

Details on the impact of addressing this CQ or CC :

As the body of evidence continues to grow on the potential applications for advanced immunotherapies, next-generation research must focus on addressing the possible curative effects that checkpoint blockades or adoptive CAR T-cell strategies can have for blood diseases including hematologic cancers. This will require specific research programs to fully understand the optimal role for these therapies within the continuum of care. To optimize these strategies for treatment of hematologic diseases, studies are needed to decipher specific hematologic diseases and circumstances under which these checkpoint blockers and CAR T-cell therapies may be employed as frontline approaches. Furthermore, while the optimal approach for these therapies is unclear, advanced studies are needed to elucidate the potential benefit in combining these promising approaches and whether patients can be better identified a priori for these therapies.

Name of idea submitter and other team members who worked on this idea : Alice Kuaban on behalf of the American Society of Hematology (ASH)

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28 up votes
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Goal 2: Reduce Human Disease

Non-Adherence of Patients with Chronic Respiratory Diseases

There are various reasons responsible for patients’ non-adherence. One of them is insufficient or lack of education about medications and equipment required for their treatment.

Submitted by (@vlady.rozenbaum)

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

Details on the impact of addressing this CQ or CC :

There is a critical need to develop uniform guidelines and handouts addressing the confusion over the proper use of medications (particularly inhalers) and equipment (i.e. oxygen). Improper use leads to diminished or no benefit, frustration, and, ultimately, even to a patient's decision to stop the treatment.

Feasibility and challenges of addressing this CQ or CC :

This is an issue that has been universally acknowledged for a number of years. With the help of patient focus groups, convened at the NHLBI, national pulmonological conferences, or at local venues around the country, appropriate materials can be created to benefit patients and reduce a huge burden on nation's economy due to decreased productivity and increase in hospital admissions.

Name of idea submitter and other team members who worked on this idea : COPD-ALERT

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Goal 3: Advance Translational Research

Develop biomarker panel to predict CVD risk in -omics era

There is a need to utilize the vast data generated in -omics research to develop biomarker panels for better prediction of cardiovascular disease (CVD) risks. •Cardiovascular diseases develop over decades and different panels of markers may be required for different stages •Lead molecules as potential biomarkers need to be selected by a panel of experts •Standard procedures about sample preparation, data acquisition, ...more »

Submitted by (@nhlbiforumadministrator)

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

Details on the impact of addressing this CQ or CC :

•Develop specific and sensitive markers for early prevention with more predictive power. Biomarkers that can detect specific perturbations in the system, such as metabolic status and vascular integrity prior to the occurrence of the diseases can be used for early preventive treatment of cardiovascular diseases.

 

•Identify vulnerable population who cannot be identified by the current LDL-HDL profiling

 

•Allow for more personalized treatment

Feasibility and challenges of addressing this CQ or CC :

•An increase in system biology studies using –omic approaches have provided huge data to mine through and find potential biomarkers, such as microRNA, DNA, lipids, proteins, and other metabolites, which can be used to assess changes proceeding cardiovascular diseases occurrence.

 

•The NIH-wide Big Data to Knowledge (BD2K) initiative launched in 2012 may have laid out some framework.

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

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Goal 3: Advance Translational Research

Genome Editing and Gene Therapy

There is a critical need for the establishment of strategies that will determine the efficacy, safety, and toxicity of genome editing techniques specifically in hematologic 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 :

Inherited monogenic hematologic diseases such as hemophilia, beta-thalassemia and sickle cell disease are prime targets for future application of genome editing technology. However, studies are still needed to advance our understanding of the biology of genome editing as well as determine which other disorders are amenable to genome editing correction. Emphasis on preclinical research that focuses on determining the accuracy, safety and efficiency of this technology in order to help minimize off-target mutations and reduce toxicity, is essential for effective translation of this technology into the clinic. Once preclinical efficacy is established, support will be needed for clinical vector production, toxicity testing of the vectors/reagents used, and the performance of clinical trials. The gene correction strategies developed for inherited disorders will also be attractive for other hematologic diseases, and autoimmune disorders like lupus, rheumatoid arthritis, and type I diabetes). There is also a critical need for supporting preclinical validation studies, scale-up and GMP cell manufacturing, all of which could be shared infrastructures across multiple diseases in the NHLBI portfolio.

Name of idea submitter and other team members who worked on this idea : Alice Kuaban on behalf of the American Society of Hematology (ASH)

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Goal 3: Advance Translational Research

Leveraging PEPFAR infrastructure for CVDs

How do we go about leveraging existing infrastructure, such as PEPFAR, to reduce the risk of HLBS diseases among HIV patients and other vulnerable populations? • Common goals and deliverables between NHLBI and partners will need to be identified • The best return on investment of NHLBI funds will need to be determined • Feasible T4 translation interventions in PEPFAR funded studies utilizing HIV populations with HLBS ...more »

Submitted by (@nhlbiforumadministrator)

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

Details on the impact of addressing this CQ or CC :

• Decrease the burden of heart, lung, blood, and sleep diseases in studies funded by PEPFAR in HIV populations

• Lessons learned could be expanded to HIV populations outside of Africa

• T4 translation interventions in these populations could help reduce risk factors for heart, lung, blood, and sleep diseases leading to better health outcomes

Feasibility and challenges of addressing this CQ or CC :

• PEPFAR has identified and recruited existing HIV populations in Africa which can be leveraged by NHLBI for heart, lung, blood, and sleep chronic disease research

• Infrastructure that has received PEPFAR investments can also be leveraged to undertake T4 translation interventions

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

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Goal 1: Promote Human Health

Epigenetics and Genomics

There is a need to investigate hemoglobin biosynthesis in order to develop novel approaches to treat sickle cell disease, thalassemia, and other anemias.

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

Details on the impact of addressing this CQ or CC :

Studies on epigenetic mechanisms have extraordinary promise for the development of transformative therapeutic approaches for non-malignant hematologic disorders, however, limited progress has been made in advancing therapies to counteract the often crippling complications of these conditions. In the case of sickle cell disease, an ensemble of proteins has been implicated in mediating the epigenetic repression of gamma-globin expression, raising the possibility that antagonizing the actions of these proteins to increase gamma-globin expression may be a useful treatment strategy. However, in certain cases, some of these proteins are deemed “undruggable,” based on their structural attributes. There is a critical need to identify druggable components of the multi-step epigenetic mechanisms as well as develop better models and assays that will more effectively identify modulators of “undruggable” proteins. Given the rich proteome and improved technologies available today, studies of proteomics, metabolomics, and regulatory RNAs are likely to reveal promising translational avenues. In addition, approaches to modifying the expression of the components of this pathway are underway using developing gene therapy strategies, such as viral vectors and/or gene editing can quickly advance therapy in sickle cell disease and β-thalassmia.

Name of idea submitter and other team members who worked on this idea : Alice Kuaban on behalf of the American Society of Hematology (ASH)

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62 up votes
20 down votes
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