Showing 4 ideas for tag "marrow"

Goal 1: Promote Human Health

How do Circulating Precursor Endothelial Cells contribute to newly formed vessels

Endothelial cells derive from cells in the bone marrow. Circulating precursor endothelial cells contribute to newly forming vessels.

Do Alk 1 and/or Endogln mutations affect the functions of these cells once they incorporate into growing vessels. These vessels then go on to form arteriovenous malformations

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 Marianne Clancy MPA, Chris Hughes PhD

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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?

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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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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Goal 3: Advance Translational Research

How can we develop more selective immunosuppression for allogeneic hematopoietic cell transplantation?

Graft versus host disease (GVHD) remains the most significant complication of allogeneic hematopoietic stem cell transplantation (HCT). While the use of HCT has grown significantly safer and has demonstrated broad efficacy in the setting of a broad range of blood diseases, immunosuppressive therapy has not dramatically evolved since the introduction of calcineurin inhibitor-based approaches decades ago. The availability... 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

GVHD remains a critical problem and major barrier to the more widespread utilization of HCT, especially for nonmalignant diseases, where tolerance of treatment-related mortality is understandably low.

There is a compelling need for novel immunosuppressive agents that can effectively limit alloreactivity mediated by donor T and B cells, while relatively sparing pathogen-specific T cells, including those mediating antiviral T cell responses important in the post-HCT interval.

In the past decade, drug development has facilitated the introduction into preclinical and clinical trials of a broad range of agents that in addition to targeting pathways of interest in target cells (e.g., aberrant signaling in cancer cells) may also effectively inhibit T and/or B cell responses. Examples include hypomethylating agents (e.g., azacitidine), HDAC inhibitors (e.g., vorinostat), MEK inhibitors (e.g., trametinib) and BTK inhibitors (e.g., ibrutinib). Each of these classes of agents has been demonstrated in preclinical and/or clinical studies to also limit alloreactive T cells, and/or augment regulatory T cell responses, leading to a net reduction of alloreactivity. Unlike traditional agents (e.g., the calcineurin inhibitors) these agents appear to be more selective, and in some cases may have dual benefit in reducing relapse.

The NHLBI can facilitate the identification and translation to clinical practice in the setting of HCT trials of novel immunosuppressive agents.

Feasibility and challenges of addressing this CQ or CC

Research funding targeted to improving the pipeline of novel immunosuppressive agents could have immediate and dramatic impact in the field of HCT, especially impacting its application for nonmalignant diseases. Patients lacking optimal registry donors, especially those from underrepresented minority groups, will particularly benefit from improvements in immunosuppression, as patients receiving less than optimally matched donors are at much higher risk of GVHD.

The NHLBI can encourage and facilitate research that tests compounds that have already passed through the drug development process, but in many cases were not intended to function as immunosuppressive agents. Compelling preclinical studies have suggested that targeted inhibition of T and B cells, and/or epigenetic modifiers can lessen alloreactivity while preserving beneficial cellular immune responses and facilitating immune reconstitution.

It will be far easier to appropriate therapeutic agents already developed for another purpose than to do novel drug development from scratch. In many cases, preclinical studies have highlighted the therapeutic potential in immunosuppression for agents that have been developed to treat malignancies, but yielded suboptimal success. Research that encourages the development of these drugs as part of a combined immunosuppressive/immunomodulation approach may rescue such compounds, while yielding potential dramatic advances in clinical HCT.

Name of idea submitter and other team members who worked on this idea Krishna Komanduri, M.D.

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