Goal 2: Reduce Human Disease

What do the newer treatments in R&D tell us about the management of SCD?

What is the molecular mechanism by which new drug therapies propose to reduce the severity and duration of hospitalization and opioid pain medicines? And how does that impact the course of disease progression?

Submitted by (@sicklecellwarrior)

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 : Sickle Cell Warriors, Inc. community members

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11 net votes
20 up votes
9 down votes
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Goal 3: Advance Translational Research

Using "omics" technologies to define responders to drug therapies

Metabolomic and proteomic technologies open tremendous avenues to define at the systemic level and, in the case of the lung, the organ level response to drug and non-drug interventions. The concept of responders and non-responders to therapies is poorly defined and hampers development of biomarkers and appropriate animal models. Omics technologies can bridge these important areas. In lung disease, breath analysis could ...more »

Submitted by (@njkenyon)

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

Feasibility and challenges of addressing this CQ or CC :

This work would be slow because it requires analyzing profiles of metabolomes from many drug classes. This long term project is needed to better understand the biological effects of new drugs coming to market.

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

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7 net votes
13 up votes
6 down votes
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Goal 3: Advance Translational Research

Substituting scientific-medical insight before profit in drug development

Since the Pure Food and Drug Act of 1906 and the rise of the FDA, the US federal government has directly inserted itself into medical research, primarily from a business perspective. The Orphan Drug Act of 1983 monetarily incentivized the process for rare diseases, but for ultra-rare diseases of < 1,000 patients, it does not work. Successful drugs for rare diseases have enormous price tags to compensate their development ...more »

Submitted by (@mtothbsf)

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

Details on the impact of addressing this CQ or CC :

By harnessing the vast resources of US biomedical research and biomedical researchers, many of whom were trained with NIH funding, the US can more effectively translate scientific discoveries into clinical benefit--many treatments for many diseases using many PIs. While the monetary profit incentive has been a vital aspect of pharmaceutical development over the last 50 years, in this era of personalized medicine it may not be as relevant. The individual PI with a good idea and sound scientific background may hold the key to a cure for a rare or personal disease, but is prevented from translating this because of ignorance, lack of institutional support, or the need for substantial capital investment to perform a proper clinical study. The FDA could recalibrate its requirements for clinical studies to allow even a single PI to test their idea economically, and perhaps offer the funding to do it properly. It should not go unnoticed that by understanding and treating a specific rare disease, the medical world may use this knowledge to better understand and treat diseases that affect larger numbers of people. For example, understanding or treating heart failure in a specific rare disease, may offer benefits to the larger group of heart failure patients.

Feasibility and challenges of addressing this CQ or CC :

Meeting this challenge will require a major rethinking of the traditional FDA approach of drug development and testing in humans at least for the non-profit or single PI scenario. For ultra-rare diseases of < 1,000 individuals there seems little hope that the for-profit sector would choose to be involved. For that reason and to take advantage of the enormous biomedical research resources the the US federal government has sponsored though the NIH, the US could advance translational research and usher in an era of true "personalized medicine'.

Name of idea submitter and other team members who worked on this idea : Matthew J. Toth, PhD, Science Director, Barth Syndrome Foundation Inc.

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6 net votes
11 up votes
5 down votes
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Goal 2: Reduce Human Disease

Drug Desensitization Protocols

As the current chair of the Research and Training Division, I would like to convey that the AAAAI membership would like the NHLBI to consider the following in the development of its strategic plan: Given that increasing number of patients allergic to their best medications are treated with desensitization, which allows improved quality of life and prolongs their lives,  what  personalized, effective and safe protocols ...more »

Submitted by (@wheeze)

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 : Mitchell Grayson on behalf of the American Academy of Allergy, Asthma, and Immunology

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-9 net votes
4 up votes
13 down votes
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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.

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 :

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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73 net votes
92 up votes
19 down votes
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Goal 2: Reduce Human Disease

Consequences of drug interactions leading to QTc prolongation

Better understand the consequences of drug interactions leading to QTc prolongation. About 1/3 of cardiac ICU patients develop QT prolongation and about 45% receive drugs that are possibly contributing to this problem. The full spectrum of contributors and causes, as well as the patient-centered and health-system-centered clinical outcomes, are not known.

Submitted by (@greg.martin)

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

Details on the impact of addressing this CQ or CC :

Reduction in adverse drug events and preventable deaths

Feasibility and challenges of addressing this CQ or CC :

Combining the power of predictive analytics of high dimensional data streaming continuously from critically ill patients, combined with precision medicine genomics and metabolomics, makes this imminently feasible.

Name of idea submitter and other team members who worked on this idea : Society of Critical Care Medicine Executive Council

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-1 net votes
1 up votes
2 down votes
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Goal 3: Advance Translational Research

Arrhythmia Therapies Based on Understanding Mechanisms

There is a need to translate these new insights of genetic, molecular, cellular, and tissue arrhythmia mechanisms into the development of novel, safe, and new therapeutic interventions for the treatment and prevention of cardiac arrhythmias.

Submitted by (@nhlbiforumadministrator1)

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

Details on the impact of addressing this CQ or CC :

Reduced socioeconomic burden of cardiac arrhythmias. Development of new technologies and recognition of new arrhythmia mechanisms.

Feasibility and challenges of addressing this CQ or CC :

Several studies have already recognized the unexpected antiarrhythmic effects of some therapies intended for other cardiovascular disease. For example statins, aldosterone blockers, and possibly some essential fatty acids may reduce arrhythmia burden in patients receiving these interventions. Clinical trials should be developed to demonstrate the efficacy of these interventions, and arrhythmia endpoints, including those for atrial fibrillation and sudden cardiac death, should be incorporated into other large clinical trials. Research into novel antiarrhythmic might focus on (a) drug development; (b) cell/gene-based therapy and tissue engineering; and (c) improvements in development and use of devices and ablation to prevent or inhibit arrhythmic electrical activity. Continued research might also focus on targeting of upstream regulatory cascades of ion channel expression and function. Continued antiarrhythmic strategies might include the exploration of novel delivery systems (e.g., utilizing advances in nanotechnology and microelectronics), biological pacemakers, AV node repair/bypass, and treatment and/or reversal of disease-induced myocardial remodeling and tachyarrhythmias. Evaluation of new therapies should include a cost analysis. Studies in both children and adults with congenital heart are needed. New interventions might include new pharmacologic approaches as well as advances in electrophysiologic imaging and improved approaches to ablation.

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

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51 net votes
86 up votes
35 down votes
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Goal 3: Advance Translational Research

Genome Profiling

What structural changes need to be implemented in the health-care community in order to support the use of genomic information in clinical trials and drug development for 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 :

In various blood disorders, including hematologic malignancies, there are both inherited and somatic genetic alterations that contribute to predisposition, transformation, disease progression, responsiveness to therapy, and treatment complications. The presence of such genetic alterations underscore the need for the identification of rare but traceable mutations as well as the integration of such genomic information into clinical trials. By implementing a few structural changes in the healthcare sector, a clinical trial infrastructure can be established that accounts for proper application of sequencing technology. Some examples include the creation of genome diagnostic networks that address accrual of sufficient patients, procurement of suitable tumor/non-tumor material for sequencing, as well as pharmacodynamic and correlative biology studies in hematologic diseases.

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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11 net votes
22 up votes
11 down votes
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Goal 2: Reduce Human Disease

Open up NCATS

The NCATS program for drug repurposing is currently only open to drugs submitted by industry (read, big Pharma). We have had the experience of working to repurpose a generic drug not on their list, and despite great Preliminary data, we could not. This program is a great idea, but needs to be opened to any company and any drug for which solid data backing efficacy and market can be applied. Why do we only want to enhance ...more »

Submitted by (@wjones7)

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

Details on the impact of addressing this CQ or CC :

Opening the program to all FDA approved drugs would benefit development of the most useful repurposed therapeutics. The goal should not be focused upon drugs that large corporations still hold license to, but opened to therapeutic development that helps people, regardless of the size of the corp. Another advantage is that the program could then help small companies, startups, and generic companies develop new uses for drugs proven safe.

Feasibility and challenges of addressing this CQ or CC :

Of course, large corporations can claim that they have the best chances of marketing a repurposed drug, therefore investment should be in areas and drugs they control. The reality is, no matter which entity does the work for repurposing, a successful project will likely be bought and marketed by big Pharma anyway. So the focus should be on repurposing drugs for disease that have few therapeutic options, with exemplary benefit efficacy and low rosk, ect., The focus should not be on a list of drugs submitted by

Name of idea submitter and other team members who worked on this idea : K. Jones

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-5 net votes
5 up votes
10 down votes
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Goal 3: Advance Translational Research

Rx for HFpEF

HLBI should make it a priority to develop therapeutic options for the treatment of heart failure with preserved ejection fraction.

Submitted by (@johnrobinson)

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

Details on the impact of addressing this CQ or CC :

Heart failure with reduced ejection fraction (HFrEF), formerly called systolic heart failure, is the classical form of heart failure that is characterized by defective ventricular contraction. The most common variant of heart failure is heart failure with preserved ejection fraction (HFpEF), formerly called diastolic heart failure, characterized by resistance to ventricular filling. The prevalence of HFpEF has been rising steadily over the past two decades at a rate of increase of 1% per year, while the prevalence of HFrEF which has remained stationary. The most common causes of HFpEF are ischemia, obesity, hypertension, diabetes and ageing. Since the population is increasingly obese, hypertensive, diabetic and ageing, the incidence of HFpEF will be the dominant heart failure phenotype over the next decade. The clinical management of HFpEF is complicated by lack of therapeutic options that provide survival benefit. Therapies of proven benefit in HFrEF have repeatedly been shown to add little if any benefit in HFpEF. The prognosis of HFpEF is about the same as HFrEF, with 5-year mortality ranging from 54% to 65%.

Feasibility and challenges of addressing this CQ or CC :

Recent developments in our understanding of the molecular mechanisms of myofilament regulation and assays can be used to develop lead compounds for treating HFpEF.

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

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1 net vote
13 up votes
12 down votes
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Goal 3: Advance Translational Research

Dissemination & Implementation of new treatments and therapies in sickle cell disease

Are current advances in gene editing, new drug therapies and less restrictive BMT criteria being explained and rolled out to the sickle cell community in an effective and timely manner? When can people living with sickle cell disease experience a better quality of life on more permanent based on the treatments we already have?

Submitted by (@sicklecellwarrior)

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

Details on the impact of addressing this CQ or CC :

Bone marrow transplant criteria has become less restrictive yet there has not been a steep increase in procedures. My understanding is that a sibling or child with the trait can be a donor. At some point this treatment needs to become more widely accessible and discussed with all patients by their doctors.

Name of idea submitter and other team members who worked on this idea : Sickle Cell Warriors, Inc.

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46 net votes
55 up votes
9 down votes
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Goal 4: Develop Workforce and Resources

Training in Small Molecule Discovery and Development

The current generation of heart,lung, and blood investigators are not equipped with competitive training needed to approach, design, and test appropriately small molecule therapeutics that may move through the FDA pipeline. Appropriate in silico ligan or structure based design, HTS, design of Pd/Pk models, "go-no-go" branchpoints in drug development, screening approaches, and drug target validation are issues that are ...more »

Submitted by (@mallampallirk)

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 incorporation of workshops, traditional funding mechanisms (T32, F32 etc) earmarked for this type of training will help position and equip NHLBI investigators to more effectively navigate through the landscape of drug discovery and development.

Name of idea submitter and other team members who worked on this idea : Rama Mallampalli, MD

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3 net votes
10 up votes
7 down votes
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