Showing 155 ideas for tag "disease"

Goal 2: Reduce Human Disease

Cardiometabolic Disease Risks Associated with Sleep Deficiency

How does insufficient sleep duration, irregular timed sleep schedules, and poor sleep quality contribute to the pathophysiology of lung, heart and blood diseases?

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

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Sleep deficiency and untreated sleep disorders threaten the health of 20-30 percent of US adults through an increased risk of stroke, hypertension, diabetes, inflammatory disease, and all-cause mortality. Developing the scientific evidence-base of validated interventions will enhance the management of cardiometabolic and pulmonary risks to health, present new opportunities for secondary prevention, and reduce associated burden on health care systems.

Feasibility and challenges of addressing this CQ or CC

Improving sleep health through informed public recognition of decision-relevant science, and relatively low cost therapies for management of sleep disorders are available for immediate assessment of impact in appropriate clinical trials to demonstrate efficacy and effectiveness.
Discovery research advances implicate an array of cellular sleep and circadian mechanisms in pathophysiological pathways leading to cardiometabolic and pulmonary disease.

Irregular and disturbed sleep impairs cellular biological rhythm in all tissues and organs leading to oxidative stress, unfolded protein responses, and impaired cell function. The pathophysiological findings juxtaposed with epidemiological evidence of disease risk indicate that sleep deficiency contributes to an erosion of health across the lifespan over and above the effects of aging.

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

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94 net votes
122 up votes
28 down votes
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Goal 3: Advance Translational Research

Bone Marrow Stem Cell Transplant in Peds sibling matched SCD

There is a need to improve accessibility of Bone Marrow Stem Cell Transplantation (BMSCT) for Sickle Cell Disease patients who are most likely to benefit from this treatment option.

1. Building a culture of trust between and among primary care providers, specialists, patients/families, and other stakeholders

2. Consensus building around BMSCT as an acceptable treatment alternative (as opposed to another research endeavor)... 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
  1. It could potentially decrease the prevalence of SCD and significantly decrease the overall morbidity and mortality associated with SCD in children with matched sibling donors.
  2. It could increase the awareness of health professionals who have a low awareness of the role of BMSCT in the treatment and cure of SCD (i.e., those in rural areas)
  3. It can improve patient/family access to information and communications to facilitate informed discussion and choice for all SCD treatment options
  4. It could open the gateway for more therapeutic applications for other genetic diseases
Feasibility and challenges of addressing this CQ or CC
  1. The science in this has evolved substantially such that BMSCT is a viable therapeutic option with reduced morbidity and mortality in the sibling matched population
  2. There is an opportunity to broaden current collaborations with other agencies and the BMSCT community to expand the accessibility of their research forward.
  3. Other agencies are emphasizing work in the area of BMSCT particularly for hemoglobinopathies.

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

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52 net votes
80 up votes
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Goal 2: Reduce Human Disease

Can Psychological Science Improve Weight Loss?

Will sensitivity to the psychological aspects of obesity, including lifestyle priorities and motivations, improve the efficacy of long-term effectiveness of weight loss and obesity prevention interventions?

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

Details on the impact of addressing this CQ or CC

A primary focus on principles of psychology may result in significantly improved control of the obesity epidemic. Effective interventions could reduce the risk of diabetes, sleep apnea, and hypertension. This research could also affect clinical practice guidelines for weight loss and obesity treatment.

Feasibility and challenges of addressing this CQ or CC

Psychological science has been successful in developing effective treatments for a number of conditions, including sleep disorders, depressive symptoms, anxiety and phobias. Many of the behavioral principles employed in such interventions (e.g., cognitive restructuring, motivational methods) could be translated for the prevention and treatment of obesity within a reasonable time frame. Additional attention should be directed to the needs of population subgroups in which obesity is most prevalent.
In their Viewpoint article on weight loss intervention research, Pagoto and Appelhans (JAMA, 2013, see attachment) question whether a continued focus on dietary factors in research on weight loss and obesity is warranted. Their commentary raises the importance of attention to the individual psychological characteristics that influence adherence to weight loss interventions rather than dietary composition.

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

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51 net votes
104 up votes
53 down votes
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Goal 2: Reduce Human Disease

Funding for Cardiothoracic Surgery Research

The continued development of new technologies requires cardiothoracic surgeons to maintain a strong level of research to ensure the highest quality of patient care and surgical outcomes are received across the world. The level of support for CT surgery within the NIH has continued to drop over the last decade. This is a substantial problem for the specialty as the limited funding available creates difficulty in the continued... more »

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

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CT Surgeons are performing procedures on some of the sickest patients while effecting some of the most dramatic favorable outcomes and the continue support for research in this specialty is essential to ensuring improvements in quality patient care. CT surgeons are provided the opportunity to participate in both the research lab and operating room which provides an important opportunity for a role in both the scientific discovery and implementation of new outcomes.

Feasibility and challenges of addressing this CQ or CC

Cardiothoracic diseases are one of the top health issues facing the global population and the research being conducted is integral in helping cure the issues facing the current generation. With expanded support for research, new areas of the heart, lung, and esophagus can be studied with the hopes of identifying new technologies and procedures to help ensure the next generation is given the highest quality of care possible.

Name of idea submitter and other team members who worked on this idea Matt E.

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155 up votes
50 down votes
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Goal 2: Reduce Human Disease

Predictors of Sickle Cell Disease Severity

Can better predictors of disease severity such as specific biomarkers and/or genetic polymorphisms be identified so as to help understand the course and progression of sickle cell disease in various patients?

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

Details on the impact of addressing this CQ or CC

The high clinical variability in sickle cell disease (SCD) and the lack of sufficient data to help understand and or predict the course of an individual’s disease warrants the identification of better predictors of disease severity. The identification of predictors of disease severity, such as biomarkers, will be vital in the management and treatment of SCD, especially since more recently several plasma biomarkers and certain genetic polymorphisms have been proposed to influence specific clinical outcomes, including stroke, sickle cell nephropathy, and survival. Furthermore, studies of biomarkers or genetic markers in the context of clinical drug trials may be helpful in predicting response rates, thus allowing for more personalized therapeutic decisions.

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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58 net votes
76 up votes
18 down votes
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Goal 2: Reduce Human Disease

Optimization of Existing Therapies for Sickle Cell Disease

How can the safety, dosing and benefits of existing therapies for sickle cell disease such as hydroxyurea, be optimized in order to increase its efficacy and improve patient adherence?

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

Details on the impact of addressing this CQ or CC

Hydroxyurea is a widely available disease-modifying therapy for sickle cell disease (SCD), but its effectiveness is currently limited by inadequate utilization, and less than optimal response. Research is needed to improve adherence to this evidence-based therapy and emphasis needs to be placed on determining whether therapy with hydroxyurea can prevent or even reverse organ dysfunction. In addition, research identifying new adjunct therapies to blood transfusion and hydroxyurea, as well as disease-specific therapies for co-morbidities such as kidney disease, hypertension, obstructive lung disease, and pulmonary hypertension will be valuable in the management and treatment of SCD.

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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54 net votes
74 up votes
20 down votes
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Goal 1: Promote Human Health

Transformative Impact of Proteomics

The proteomics field has dramatically progressed over the past 20 years, with advancements and improvements in experimental designs and sample preparation protocols, as well as mass spectrometry equipment, approaches, and analysis. This has resulted in substantial forward progress towards a proteomic pipeline to establish cause and effect mechanisms of cardiovascular disease. There is a need for CV proteomics that resolve... 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 necessary tools have been assembled, and managing implementation will reduce the time required for completion of larger scale projects.

Feasibility and challenges of addressing this CQ or CC

high feasibility; the challenge will be managing communication across groups to maximize impact

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

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196 net votes
234 up votes
38 down votes
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Goal 2: Reduce Human Disease

Does lowering circulating lipoprotein(a) levels influence cardiovascular outcomes?

A comprehensive research strategy and plan is needed to determine the most efficient, safe, cost-effective and widely applicable strategy to decrease circulating levels of lipoprotein(a) and to determine whether lowering circulating lipoprotein(a) levels will reduce the risk of developing cardiovascular disease such as a heart attack or a stroke as well as the progression of atherosclerosis or aortic stenosis.

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

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Approximately 20% of the population are characterized by elevated circulating levels of lipoprotein(a), regardless of age, gender or blood cholesterol levels. Estimates suggest that up to 90% of the variation in plasma lipoprotein(a) levels could be due to genetic factors, which makes lipoprotein(a) the most prevalent inherited risk factor for cardiovascular diseases (CVD). Large-scale genetic studies have shown that Lipoprotein(a) was the strongest genetic determinant of CVD such as atherosclerosis and aortic stenosis. Lipoprotein(a) is one of the strongest predictors of residual CVD risk and has been shown to improve CVD risk prediction in several population-based studies. Lipoprotein(a) is also one of the strongest known risk factors for spontaneous ischemic stroke in childhood.
A comprehensive research strategy aiming at identifying, evaluating interaction with other risk factors, treating and educating patients with elevated lipoprotein(a) levels would result in substantial reductions of health care costs in the US and around the globe by reducing the burden of CVD while simultaneously improving the quality of life of these patients.

Feasibility and challenges of addressing this CQ or CC

The list of pharmaceutical agents that reduce lipoprotein(a) levels is steadily increasing. There are approximately half a dozen strategies that have been shown to significantly and safely lower lipoprotein(a) levels. One of the challenges of this research strategy will be to determine which of these strategies represent the most efficient, safe, cost-effective and widely applicable approach to lower lipoprotein(a) levels and CVD outcomes.
Increasing awareness on lipoprotein(a) and CVD will also be of utmost importance for this effort as relatively few physicians perform lipoprotein(a) testing and even fewer patients are aware of their lipoprotein(a) level. The first sign of high lipoprotein(a) is often a heart attack or stroke. Our challenge will be to identify patients with high lipoprotein(a) that could be enrolled in trials of risk characterization and lipoprotein(a)-lowering.

Name of idea submitter and other team members who worked on this idea Sandra Revill Tremulis on behalf of the Lipoprotein(a) Foundation Scientific Advisory Board

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235 net votes
297 up votes
62 down votes
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Goal 2: Reduce Human Disease

Apheresis Medicine in the Management of Sickle Cell Disease

Despite advances in care, patients with sickle cell disease have significant morbidity and mortality. One challenge is the optimal use of simple vs exchange transfusion vs no transfusion when managing these patients. Simple transfusions lead to iron overload while exchange transfusions may expose patients to increase numbers of red blood cell units. The mechanism of benefit from transfusion (oxygen delivery vs marrow... 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

SCD is the most common genetic disease in the United States affecting 100,000 individuals or 1 in 400 African American births. Pain, stroke, acute chest syndrome and priapism are common morbidities affecting patients with sickle cell disease, which often result in emergency room visits and/or hospitalizations. Despite advances in treatment, sickle cell disease is associated with significant mortality and shortened life expectancy. Defining the optimal role of red blood cell exchange and plasma exchange (which may be used to remove plasma molecules such as inflammatory factors and free hemoglobin) in the management and prevention of the complications of sickle cell disease and may not only prolong the life of these patients but is expected to improve the quality of their lives. In addition, clearly defining the indications for simple verses exchange transfusion therapy has the potential to minimize both alloimmunization to red blood cells (reported to occur in up to 75% of patients with sickle cell disease) and iron overload associated with transfusion.

Transfusion therapy may be efficacious to sickle cell patients by providing increased oxygen delivery to tissues and/or decreasing the amount of sickle hemoglobin present by suppression of erythropoiesis. Understanding the relative contributions of these mechanisms will assist with optimal use of transfusion therapy as well as inform the development of novel alternative therapies

Feasibility and challenges of addressing this CQ or CC

Multi-center trials should be feasible, given the number of patients with sickle cell disease in the US. Participation by larger academic centers which care for sickle cell patients should facilitate trials. Methods for automated red cell exchange and plasma exchange are available and in common use at many centers. Great interest exists among physicians caring for sickle cell patients (as exemplified by the recent NIH consensus document and ASFA sickle cell consensus conference) which is a strength of this proposal. Challenges include agreement on standard treatment protocols across centers and long term follow up of patients. Maintaining vascular access in sickle cell patients is another challenge when performing apheresis procedures on sickle cell patients

Name of idea submitter and other team members who worked on this idea Bruce Sachais on behalf of ASFA

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130 net votes
152 up votes
22 down votes
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Goal 2: Reduce Human Disease

Lipid apheresis as adjunct therapy in peripheral vascular disease

What is the roll of inflammation and how does lipid apheresis alter inflammation in peripheral vascular disease when added to standard therapy and/or when used alone? Does lipid apheresis result in long-term improvement with reduced morbidity, mortality, and expense compared to standard therapy?

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

Details on the impact of addressing this CQ or CC

The prevalence of peripheral vascular disease (PVD) in the United States is estimated to be 5.9%, affecting up to 20% of adults over the age of 65. Therapy for PVD is vascular surgical intervention for limb ischemia; combined with medical therapy and anti-platelet agents but morbidity and mortality remains high. Low density lipoprotein cholesterol (LDL-c) is associated with increased risk for development and progression of PVD. Preliminary studies of the use of lipid apheresis have demonstrated improvement in symptoms and a variety of laboratory measures with decreased morbidity when added to standard therapy. The mechanism of this treatment may go beyond reducing LDL-c as the columns also affect levels of inflammatory cytokines, alter blood rheology, and affect other lipids.

Feasibility and challenges of addressing this CQ or CC

Currently two lipid apheresis devices have been cleared by the Food and Drug Administration and are in use in the United States. The presence of cleared devices, the large number of affected patients, and availability of testing for lipoproteins, fibrinogen, CRP, PAI-1, IL-6, IL-17, IL-1, IL-10, INF-γ, VEGF, PGI2, IGF-I and rheology factors make the enrollment and evaluation of patients into a clinical trial examining the use of this treatment of PVD feasible. Challenges for the performance of a clinical trial would include the limited number of centers offering lipid apheresis, the chronic nature and length of time needed to perform lipid apheresis, and the expense of the lipid apheresis devices and disposables.

Name of idea submitter and other team members who worked on this idea Bruce Sachais on behalf of ASFA

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96 net votes
116 up votes
20 down votes
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Goal 2: Reduce Human Disease

SLEEP DISORDERS AS A MODIFIABLE RISK FACTOR FOR CHRONIC DISEASE

There is developing evidence that sleep disorders, in particular obstructive sleep apnea and inadequate sleep, can influence the course of other chronic diseases. Observational studies show that CPAP treatment of patients with pre-diabetes who have OSA reduces the incidence of future diabetes. Moreover, animal and human data indicate that insufficient sleep and sleep apnea can affect the rate of progression of neurodegenerative... 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

This question will have considerable impact. Sleep apnea is an independent risk factor for insulin resistance. Moreover, observational studies show that treatment of OSA reduces the rate of future diabetes compared to that which occurs in untreated OSA. Therefore, identifying OSA and treating this could have a profound impact on reducing the rate of diabetes, i.e., a preventative strategy.

Both sleep loss and obstructive sleep apnea have also been shown to be risk factors for subsequent development of Alzheimer’s disease. This has been shown in mouse models and in epidemiological studies to address whether insufficient sleep and sleep apnea are independent risk factors for development of Alzheimer’s disease, in particular accelerating their onset. Determining whether this is so and whether interventions to treat these sleep disorders delay onset of diabetes and Alzheimer’s disease would have profound public health significance.

Feasibility and challenges of addressing this CQ or CC

These disorders are extremely common so that recruitment of subjects is not challenging. Moreover, new technology reduces protocol burden to assess individuals. All studies can be done in the patients’ home. There are existing cohort studies focused on diabetes and the Alzheimer’s Center program that could be used for these studies. Thus, the studies are extremely feasible in the near term.

Name of idea submitter and other team members who worked on this idea Sleep Research Society

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156 net votes
211 up votes
55 down votes
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Goal 1: Promote Human Health

ESTABLISH NORMATIVE AGE- AND GENDER-SPECIFIC DATA FOR SLEEP DISRUPTION, SLEEP QUALITY AND CIRCADIAN TIMING

There is growing evidence that sleep durations are progressively declining in the United States. Moreover, sleep durations are different at different ages and in different ethnic groups. Currently definitions of normal are based on consensus since there is a lack of key data. Defining normal as with FEV1 is a critical step.

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 developing evidence from both basic research and clinical research on the role of insufficient sleep in different co-morbidities. These include cardiovascular disease, hypertension and metabolic disorders. The Centers for Disease Control (CDC) has appreciated the importance of this that adequate sleep is one of the pillars of health. As part of the CDC-supported program on sleep health, a consensus statement has been issued on normal sleep duration. The group doing this on behalf of the American Academic of Sleep Medicine and Sleep Research Society realized that our evidence base is inadequate at this time. Thus, there is a need to focus on this critical challenge. Sleep duration varies across the lifespan and there is some evidence that it is different in different ethnic groups. Thus, there is a need for comprehensive efforts to address this question and to obtain normative data for sleep duration that is age-, gender-specific and with respect to different ethnic groups.

Feasibility and challenges of addressing this CQ or CC

There are now recent cohorts at NIH assessing sleep duration using not only self-report but also actigraphy. These could be used as an initial approach to address this question. This will require some degree of coordination between NIH Institutes. In the future a cohort that is specific to addressing questions about sleep duration and other sleep problems would be optimal. There are major prevalent public health issues. This would be facilitated by development of new mobile approaches to assessing these behaviors in an objective way.

Name of idea submitter and other team members who worked on this idea Sleep Research Society

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157 net votes
214 up votes
57 down votes
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Goal 3: Advance Translational Research

Increasing Regenerative Medical Strategies in Pulmonary Arterial Hypertension

Pulmonary arterial hypertension (PAH) is a complex, progressive condition characterized by high blood pressure in the lungs and restriction of flow through the pulmonary arterial system. Current PAH therapies mainly act of the vasoconstrictive component of the disease; however there is a widely accepted view that another contributor to the disease is an abnormal overgrowth of cells that line the pulmonary arteries, which... 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

In the past twenty years, 12 PAH targeted-therapies have been approved by the FDA. This increase in disease state awareness and in the treatment armamentarium have contributed to an increase in average survival from 2.8 years to an estimated 8-10 years. However, current treatments primarily address the vasoconstrictive component of the disease and do not address the now accepted theory of post-apoptotic overgrowth of hyperproliferative cells of the pulmonary vessels. A number of circulating stem and progenitor cells, derived from the bone marrow, have been identified that could have roles in repair of the pulmonary vascular system when interacting with the quickly, abnormally growing cells in the lung vessels. Work in this area has been named as a future research opportunity in the NHLBI-ORDR Strategic Plan for Lung Vascular Research (Erzurum S, et al. 2010).

Feasibility and challenges of addressing this CQ or CC

Basic and translational research support is needed—including high-throughput approaches such as phage display and large-scale proteomic analysis—to better understand the relationship between circulating bone marrow-derived cells, lung-resident stem and progenitor cells, and endothelial cells of the pulmonary arterial system.

Name of idea submitter and other team members who worked on this idea Pulmonary Hyeprtension Association, Michael Gray, Katie Kroner

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71 net votes
81 up votes
10 down votes
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Goal 2: Reduce Human Disease

Understanding the Genetic & Epigenetic Basis of Congenital Heart Disease?

Over the last thirty years, our fundamental understanding of the genetics and pathogenesis of congenital heart disease has lagged the tremendous advances in the surgical and clinical care of infants with this group of disorders. We need to close this gap with investigation into the genetic basis of congenital heart malformations to develop new models of disease. The goall is translate an improved molecular genetic and... 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

Congenital heart disease (CHD) is the most common congenital malformation and the most common cause of mortality during the first year of life. Approximately 70% of cases occur sporadically without a strong family history or identifiable genetic syndrome, and the primary heritable basis of most non-syndromic CHD has yet to be identified. Studies of affected kindreds, syndromic disease, and more recently genome wide association studies (GWAS) have shed light on a handful of causal loci, while exome sequencing and studies of structural variation uncovering rare de novo variants in trios have yielded only an 8-10% rate of diagnosis in cohorts with CHD. Despite the application of contemporary techniques and study design to genetic discovery in CHD, the majority of the genetic risk for human cardiac malformations remains unexplained.

Feasibility and challenges of addressing this CQ or CC

One key challenge is that many of the stakeholders including those affected with congenital heart disease (children), along with the physicians make a diagnosis and referral (obstetricians, neonatologists, general pediatricians), are generally funded by other agencies (NICHD). Trans-agency collaboration and cooperation is necessary to improve the translational research structures necessary to improve disease.

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37 up votes
15 down votes
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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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42 net votes
62 up votes
20 down votes
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