Showing 15 ideas for tag "therapy"

Goal 2: Reduce Human Disease

Cellular therapy of Blood Diseases

Can modification of either autologous or allogeneic immune cells allow effective treatment of blood diseases and infection with acceptable rates of toxicity?

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 targeted therapy is generally applied to the use of small molecules that target specific genes or proteins of diseased cells, it is now possible to target immune cells against specific diseases through genetic modification. This provides desired antigen-specificity to powerful cell-mediated cytotoxicity effects. Small studies show impressive results both in blood cancers and viral infections refractory to other therapies. Toxicity and efficacy vary with the diseases being treated and the cell products used. In addition, new approaches to genetically-modify blood stem cells are being evaluated to prevent viral infection, i.e. HIV, or correct hematopoietic stem cell derivatives, and these approaches could cure diseases for which good treatments are not currently available.

Feasibility and challenges of addressing this CQ or CC

Both preclinical and clinical studies are needed to identify optimal cell types and gene constructs, use of “universal” donors, and magnitude and durability of clinical effects. Effective infrastructure to provide the right cells at the right time is necessary to test clinical efficacy.

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

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98 net votes
122 up votes
24 down votes
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Goal 2: Reduce Human Disease

Immunologic Treatment of Hematologic Malignancies

How can the effectiveness of existing curative therapies be improved for allogeneic hematopoietic stem cell transplantation?

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

Details on the impact of addressing this CQ or CC

Much remains to be understood about immunotherapies in order to facilitate their broad use in the treatment of hematologic disorders. While studies to date have demonstrated significant potential applications, longer-term studies are necessary to further improve the profile of these therapies, including enhancing their overall efficacy while reducing associated toxicities. The efficacy of existing curative therapies can be enhanced by evaluating the mechanisms involved in producing cytokine release syndrome; a condition which has been observed in several patients receiving this therapy. Furthermore, a careful grading scheme to predict toxicity so as to guide the development of preventive and therapeutic strategies is also required. Target identification is another important issue to advance the field. While targeting CD19 appears to be promising, it results in loss of B-cell immunity and requires prolonged immunoglobulin replacement therapies and/or allo-transplantation and new immunologic targets need to be identified in both B cell and T cell malignancies as was as acute and chronic myeloid leukemias. Minimizing the off-tumor target-mediated toxicity of both CAR T-cell and checkpoint blockade therapies would help optimize their utility.

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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43 net votes
63 up votes
20 down votes
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Goal 2: Reduce Human Disease

How can we more safely deliver stem cells to Sickle Cell patients

Newer therapies using gene correction, rather than gene addition, are needed for sickle cell disease. Even with this potential advantage, there needs to be a way to safely deliver gene corrected HSC to the sickle cell patient. Chemotherapy is poorly tolerated, and often is the reason patients do not choose the BMT option. What is the status of other less toxic non myeloablative approaches, and how can they best be... 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

would open up opportunities for more patients to get cured of their sickle cell disease without co morbidity of the BMT process

Feasibility and challenges of addressing this CQ or CC

Need to develop animal models and also newer marrow niche clearing agents.

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51 net votes
67 up votes
16 down votes
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Goal 2: Reduce Human Disease

The Use of Therapeutic Apheresis to Reduce Circulating Levels of Galectin-3 and other Cancer and Inflammation Promoting Factors

Inflammation plays roles in cancer initiation, promotion, and progression. Elevated circulating galectin-3 (Gal-3) protein and other cancer and inflammation promoting factors (CIPFs) such as C-reactive protein and VEGF are associated with tumorigenesis and may play causative roles. Plasma Gal-3 is a biomarker, prognosticator, and pathogenic mediator of diverse cancers and is emerging as a therapeutic target. Preliminary... 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

Apheresis therapy in a clinical setting, both alone and in combination with conventional protocols, shows great potential to enhance treatment regimens, reduce dosage and side effects, improve drug deliver to target tissues, reduce long term treatment related morbidity and improve outcomes with significant benefits for patients with a broad range of cancer types and stages.

Feasibility and challenges of addressing this CQ or CC

The need for well designed, randomized clinical trials would be readily feasible with the appropriate IND. Grant support will be needed for further development of this concept, as well as to develop columns with more optimized and specific capabilities, in addition to clinical trials demonstrating efficacy.

Apheresis is highly underutilized and underfunded in the US, while Apheresis research and development is much more advanced and widely utilized in Europe and Asia.

Name of idea submitter and other team members who worked on this idea Isaac Eliaz, MD

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33 net votes
40 up votes
7 down votes
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Goal 2: Reduce Human Disease

A Program of Research in the Prevention of Chronic Heart Failure

There is a need to address chronic heart failure (HF) through improved identification of patients at risk for HF and of patients with pathological ventricular remodeling who have minimal evidence of clinical HF, and more focused and individualized pharmacologic and lifestyle treatments and monitoring of patients with HF risk. Approaches would include big data collection, omics, statistical modeling, and focused clinical... 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

Substantially reduce the age-adjusted incidence and population burden of chronic heart failure.

Feasibility and challenges of addressing this CQ or CC

The big data and omics revolutions have made it feasible to collect and analyze a variety of data in large numbers of persons within a relatively short time. A very large sample size provides excellent statistical power. Also, the public health and economic magnitude of the problem create the urgency needed to address the critical challenge expeditiously.
Chronic heart failure (HF) is easily the most common and growing cardiovascular cause of hospitalization and impaired functional status and quality of life in the U.S. and much of the world. This is the case despite improved pharmacologic and lifestyle treatment of HF, as well as improved control of blood pressure in the general population. While some HF in the very elderly may reflect the aging process, the epidemiology suggests that most incident cases could be prevented or postponed for years. Also, there are major ethnic and socioeconomic disparities in the incidence of HF.

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

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17 net votes
28 up votes
11 down votes
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Goal 2: Reduce Human Disease

A Program of Research in the Prevention of Chronic Heart Failure

There is a need to improve identification and surveillance of persons at risk for heart failure and pathological ventricular remodeling prior to development of clinically overt heart failure.

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

Details on the impact of addressing this CQ or CC

Substantially reduce the age-adjusted incidence and population burden of chronic heart failure.

Feasibility and challenges of addressing this CQ or CC

The big data and omics revolutions have made it feasible to collect and analyze a variety of data in large numbers of persons within a relatively short time. A very large sample size provides excellent statistical power. Also, the public health and economic magnitude of the problem create the urgency needed to address the critical challenge expeditiously.
Chronic heart failure (HF) is easily the most common and growing cardiovascular cause of hospitalization and impaired functional status and quality of life in the U.S. and much of the world. This is the case despite improved pharmacologic and lifestyle treatment of HF, as well as improved control of blood pressure in the general population. While some HF in the very elderly may reflect the aging process, the epidemiology suggests that most incident cases could be prevented or postponed for years. Also, there are major ethnic and socioeconomic disparities in the incidence of HF.

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

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14 net votes
28 up votes
14 down votes
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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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13 net votes
28 up votes
15 down votes
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Goal 2: Reduce Human Disease

Treatment of Major Depression in Patients with Heart Failure

Major depression (MD) is common in patients with heart failure, and it is an independent risk marker for functional decline, hospitalization, and mortality. Two large trials have shown that it can be difficult to treat. SADHART-CHF, a double-blind, placebo-controlled RCT (n=469), found that sertraline was not efficacious for MD in HF. MOOD-HF (n=372) showed that escitalopram was not efficacious. Smaller trials of cognitive-behavioral... 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

Major depression causes considerable emotional distress and functional impairment. It follows a chronic or recurrent course in many cases, and untreated episodes can last for months or even years. When superimposed on chronic heart failure, major depression can accelerate functional decline, diminish quality of life, and increase the risks of hospitalization and mortality. Effective treatment of depression can, at minimum, improve quality of life. Treatment may also decrease the risk of adverse medical outcomes, but RCTs will be needed to evaluate the potential medical benefits of treating depression in HF.

Feasibility and challenges of addressing this CQ or CC

Cognitive behavior therapy is the most promising approach tested so far, but there have been few trials of this intervention, any other psychotherapeutic treatment for depression, or antidepressant medications other than sertraline or escitalopram for major depression in HF. Additional phase II trials may be needed in order to identify the most promising approaches for testing in larger, multicenter RCTs.

Name of idea submitter and other team members who worked on this idea Kenneth E. Freedland, PhD

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8 net votes
27 up votes
19 down votes
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Goal 2: Reduce Human Disease

How do Cell Therapies Really Work?

Multiple lines of evidence suggest that the beneficial effects of cell therapy are mostly indirect, but what are the key factors responsible for these indirect benefits?

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

Details on the impact of addressing this CQ or CC

Could restore lost or diminished organ function

Feasibility and challenges of addressing this CQ or CC

Extensive research infrastructure already exists and durability and quality of beneficial effects has continued to increase over time, although incrementally. Field is poised for a breakthrough with the right spark funding.
Cell-based therapies, demonstrated with a wide range of cell types, have shown glimmers of promise in HLB applications, such as improved functional recovery, reduced scar formation, and beneficial effects up to 6 months. However, transplanted cells have poor retention, minimal long-term survival, and the mechanism-of-action is unclear.

 

The challenge is to stimulate new hypotheses on the mechanism-of-action in order to achieve long-term benefits, and then to support definitive confirmatory studies. Funding already exists, but the main spark might come from encouraging other disciplines to get involved.

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

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-1 net votes
18 up votes
19 down votes
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Goal 2: Reduce Human Disease

Human Lung Progenitor Cells, Lung Epithelial Differentiated iPSCs, and Therapeutics

What are the biological properties and key surface markers of human lung progenitor cells and lung epithelial differentiated iPSCs? How can these cell populations be targeted for therapeutic purposes, including regenerative therapy?

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 Cystic Fibrosis Foundation

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2 net votes
6 up votes
4 down votes
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Goal 2: Reduce Human Disease

Reducing CV events in breast cancer survivors -knowledge gaps

Identifying breast cancer survivors at high risk for CV morbidity and mortality to allow targeting of management strategies to reduce CV events and thereby improve overall cancer-related survival.

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

Details on the impact of addressing this CQ or CC

Chemotherapy for breast cancer stages I-III is known to be associated with or induce cardiotoxicity. Over 35% of these women develop progressive fatigue and exercise intolerance, and heart failure limiting their daily activities and frequently interfering with their ability to return to work. CV disease are the leading cause of morbidity and mortality for those surviving beyond 5 to 8 years from their breast cancer diagnosis. The excess of CV morbidity and mortality in these patients threatens to offset reductions in cancer-related survival. Identifying breast cancer survivors at high risk for CV morbidity and mortality could allow targeting of cardiovascular disease reducing therapeutic interventions.

Feasibility and challenges of addressing this CQ or CC

creating a multisite registry of women with Stage 1-3 breast cancer scheduled to receive chemotherapy and a control population women of similar demographic and CV risk profile without neoplasia, would allow to collect data at baseline and during/after cancer treatment related modern therapy, pre/post treatment functional status, including fatigue, behavioral and psychosocial risk factors and quality of life, and serum biomarkers indicative of myocardial injury, fibrosis, and heart failure.

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

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-1 net votes
5 up votes
6 down votes
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Goal 2: Reduce Human Disease

Combination Cardioprotective Therapy for AMI

Which therapy or combination of therapies to reduce injury from acute myocardial infarction (AMI) will be most efficacious for future clinical trials?

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

Details on the impact of addressing this CQ or CC

AMI and heart failure continues to be a major cause of morbidity and mortality in the Western world.

Feasibility and challenges of addressing this CQ or CC

Promising cardioprotective candidates are emerging. Additional pre-clinical and clinical research is needed to further investigate these new strategies, alone and in combination, to improve outcomes following AMI.
Numerous studies have implicated various pharmacological and interventional techniques (e.g., adenosine, cyclosporine, postconditioning, and remote ischemic per-conditioning) have been explored.

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

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-7 net votes
6 up votes
13 down votes
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Goal 2: Reduce Human Disease

Gene Therapies to Revitalize/Regenerate Cardiac Function

There is a need to examine the use of recombinant DNA to the heart for correction of genetic abnormalities or restoration of normal signaling pathways to prevent heart failure. However, gene therapy is a complex process and more studies are needed in which tissue targeting, route of delivery, regulation of target gene expression, therapeutic dose, and identification of robust biomarkers are further investigated.

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

Details on the impact of addressing this CQ or CC

Successful gene therapy could restore or improve the condition of heart failure patients, especially when medications have been unsuccessful.

Feasibility and challenges of addressing this CQ or CC

There have already been human trials of gene therapy in heart failure patients with positive outcomes.
Improvements in cardiac revascularization and medical therapies have significantly reduced cardiovascular-related deaths; however, the number of patients developing heart failure (HF) has steadily increased. One explanation is that surgery and medical therapies are palliative, but do not address the molecular pathogenesis of HF.

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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