Showing 14 ideas for tag "rare"

Goal 3: Advance Translational Research

Multicenter trials of therapies for rare diseases.

Infrastructure for performing research in rare diseases should be enhanced to allow efficient accrual to multicenter trials.

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

Details on the impact of addressing this CQ or CC

Many of the malignant and non-malignant blood diseases that fall under the purview of the NHLBI are uncommon though, in aggregate, important contributors to the burden of disease in the US population. Although in some areas, like blood and marrow transplantation (BMT), there exists an infrastructure for multicenter trials, in many areas there does not. This makes testing potentially effective therapies very difficult. The large increase in the number of national BMT trials following the implementation of that network indicates the effectiveness of the approach, which could be expanded to include cellular therapies and other novel approaches.

Feasibility and challenges of addressing this CQ or CC

The current R01 process does not lend itself to efficient and rapid implementation of trials to test new approaches or to the time needed to complete trials that focus on long-term survival and quality of life endpoints. Even within the existing transplant network, efficiencies could be gained by infrastructural enhancements like a common IRB or government-assisted contracting (i.e., CRADAs), a streamlined process for protocol review (e.g. a one- versus two-step process), etc. Additionally, enhanced ability to collaborate with other organizations or institutes, without undue bureaucratic burden, would allow better use of NIH funds so that more trials could be done.

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

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Goal 3: Advance Translational Research

Stem Cell Biology

There is a need to develop “designer platelets” and “designer red cells,” as well as facilitate large-scale production of these products for therapeutic and diagnostic use.

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 reprogramming of adult stem cells has resulted in the generation of induced pluripotent stem cells (iPSCs) that can develop into any tissue of the body. These iPSCs ultimately may be used as a transplantable source of stem cells for a variety of hematologic diseases. Although this technology has enabled the generation of patient-specific or disease-specific stem cells that are also amenable to genetic manipulation, the major scientific hurdle has been the ability to create clinically meaningful functional blood products, including transplantable HSCs from differentiating iPSCs. The production of clinically functional blood products -- i.e. red blood cells derived from autologous iPSCs --could replace allogeneic products in highly immunized patients and the generation of megakaryocytes for patient-specific platelet production from iPSCs could drive significant progress in this area. Furthermore, disease-specific iPSCs could serve as targets for both drug development and drug screening in patients with rare hematologic disorders. In addition, support for scale-up and GMP processes, which are difficult to fund via the R01 mechanism will require specific grant opportunities tailored to infrastructure and process development.

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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53 up votes
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Goal 3: Advance Translational Research

Novel Mechanism for Clinical Trials of New Pro-Hemostatic Agents in Hemophilia

There are new exciting novel pro-hemostatic therapeutics in early phase clinical trials for hemophilia and hemophilia inhibitor patients. Yet, it is difficult to design randomized trials to compare these agents, or compare them with standard treatment, given the small sample size and competing studies for such patients. It is critical to develop novel approaches to compare new agents in rare populations. For example,... 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

Should rare disease-specific strategies for clinical trials be developed, it would revolutionize the approach to study of not only rare disease populations, but all disease groups, no matter their size. If validated, rare disease-specific clinical trial strategies, would potentially reduce the cost, time, patient burden, and research effort to conduct clinical trials. If validated, consideration could be given to drug licensure earlier in the trial process, with a requirement for all such trials to initiate and continue ongoing data collection post-licensure for safety and efficacy.

Feasibility and challenges of addressing this CQ or CC

Novel statistical methodologies are greatly needed to help with rare disease research. NHLBI might consider a grant mechanism RFA to encourage development of novel clinical trial strategies utilizing smaller sample size. The proof would be to develop the methodology as part of a feasibility study, and then, if feasible, adapt the novel approach to development and conduct of a clinical trial in a rare disease clinical tria,l to test the concept.

Name of idea submitter and other team members who worked on this idea Margaret V. Ragni, MD, MPH (aspects discussed with Don Brambilla PhD.

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15 up votes
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Goal 3: Advance Translational Research

In-Vitro Assays to Predict Clinical Response

How can NHLBI support studies that produce in-vitro assays to predict clinical response and ways to translate those results into patient therapies through novel clinical trials, including those for small patient populations and rare diseases?

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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6 up votes
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Goal 2: Reduce Human Disease

Rare Disease Registry

NHLBI should establish a rare disease registry.

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

Details on the impact of addressing this CQ or CC

While we agree that some registries of the past had limited utility, state of the art registries of today are different. Registries of rare diseases need support. If left to the foundations and CTSA awards, many of these registries can capture clinical and physiologic data, but struggle to fund radiological repositories and biorepositories that can capture genomic data. When I look at the landscape of those lung diseases that have nothing, the list is very long. “Idiopathic” Fibrotic NSIP, acute interstitial pneumonia, rheumatoid interstitial lung disease, acute and chronic eosinophilic pneumonia, cryptogenic organizing pneumonia, aspiration associated lung disease, radiation pneumonitis, eosinophilic bronchitis, mycobacterium avium complex, hepatopulmonary syndrome, and Churg-Strauss vasculitis while individually very rare make up 3-5% of all lung diseases. If we put 3-5% of the Lung Division budget into these diseases, the impact would be huge. Meaningful impact would include a mentorship program for patient foundations, CTSA directed collaborative biorepositories, a Rare Lung Disease Centers of Excellence program (possibly modeled after the NIH program in diseases of unknown cause), and a conference structure that is funded as a core component of the Lung Division budget. Most important is to assure that linkage to the patients who participate is assured after the collection of the biosamples is obtained.

Feasibility and challenges of addressing this CQ or CC

To the extent that you might influence NIH politics, one important impediment to this science is the inability of the NIH to keep and sustain patient identifiers. If the IRS can do it, why can’t NIH? Although I realize that this last part is out of your personal control, an internal registry mechanism sponsored by the NHLBI would transform the landscape of the institute for rare disease science. It would solve the problems associated with internal registries being unable to join with other international endeavors (NIH LAM Registry for example).

Name of idea submitter and other team members who worked on this idea ATS Member

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Goal 2: Reduce Human Disease

Hosting International Studies on Rare Diseases

A programmatic initiative that would transform the NHLBI for rare diseases is to host some international studies.

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 rest of the world is far ahead of the US in Registry science (e.g.. OrphaNet). To take a very rare disease (e.g.. Bechet’s pulmonary aneurysms, or hypocomplementemic urticarial vasculitis associated COPD) and establish an RFA to blend an international Registry with capability for hosting a clinical trial, and 3 years later an RFA to use the biorepository for proof of principal studies and a clinical trial would accelerate the international science agenda to a degree that might be unimaginable. Once established for 1 disease, the infrastructure should be kept intact for other diseases.

Name of idea submitter and other team members who worked on this idea ATS Member

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Goal 2: Reduce Human Disease

Rare Diseases

A study section should be seated for clinical trials on rare disease. Members of this study section should consist only of individuals who have previously performed phase I and/or phase II trials, developed IND or IDE applications, or who have extensive experience in informatic or biometric support for clinical trials. My opinion is that seating individuals on these sections who have a laboratory career in cellular or... more »

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

Name of idea submitter and other team members who worked on this idea ATS Member

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Goal 2: Reduce Human Disease

Interaction with Office of Rare Diseases

NHLBI should engage more interactively with the Office of Rare Diseases (ORD).

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 synergy that comes with collaboration with rare disease clinical science from other institutes. Some of this synergy is scientific, much of it falls into the support engendered to the patient support groups that are partners in filling the funding gap that many NHLBI initiatives have.

Feasibility and challenges of addressing this CQ or CC

To go it alone in rare disease dissociates the lung disease clinicians from the huge movements in registry science that will impact the field for years to come.

Name of idea submitter and other team members who worked on this idea ATS Member

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Goal 1: Promote Human Health

Re-examining Antigenicity of Rare Blood Disease Proteins

What specific roles do protein glycosylation and protein complex formation on stable and activated cellular membranes play in inherent immunogenicity and antibody formation to life-saving therapies for rare blood disorders?

 

NHLBI leadership and collaboration with NIAID is needed to bring this combined expertise to bear on the understanding and prevention of this most significant complication of hemophilia 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

Inhibitory alloantibody formation to critical life-saving therapies impedes effective replacement therapy in up to 30-40% of children and adults with congenital blood diseases, thereby significantly increasing the complications of the underlying disease. For children with hemophilia A, this treatment complication has significantly limited the impact of the last 20 years of therapeutic advances in product efficacy and safety. Discovery science in this area has focused on the relationship between the immune response and treatment circumstances, and the epitope specificity of the targeted immune response. However, this scientific pathway to discovery has not yielded the critical mechanistic data required to inform effective prevention strategies. Recent advances in our understanding of the co-factors for immunogenicity, the biochemistry of coagulation factor complex formation on cellular membranes, glycobiology and gene transfer must now converge to create a potential platform for exploring new paradigms of immunogenicity, and thus leading to new strategies for inducing tolerance to future new therapeutics in hemophilia.

Feasibility and challenges of addressing this CQ or CC

A recent workshop sponsored by the National Hemophilia Foundation highlighted the threat to novel therapies for hemophilia as well as curative gene therapy from the unsolved problem of replacement protein or gene product antigenicity. However recent advances in our understanding of the co-factors for immunogenicity, the biochemistry of coagulation factor complex formation on cellular membranes, glycobiology and gene transfer, can now converge to create a potential platform for exploring new paradigms of immunogenicity, and thus leading to new strategies for inducing tolerance to future new therapeutics.

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

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8 up votes
9 down votes
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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?

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 2: Reduce Human Disease

Rare Disease Biorepository

NHLBI should establish a rare disease biorepository that can be used by PhD and MD scientists, and propose new therapies based on the insights gained.

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 you think about improving rare disease treatment, any clinical trial is better than no clinical trial. Although I make this point in jest, the important aspect is that the control group is actually as important as the treatment group in establishing the natural history of the disease, establishing a biorepository that can be used by PhD and MD scientists, and proposing new therapies based on the insights gained. I would use as an example the current GRADS program in sarcoidosis and Alpha-1 antitrypsin deficiency. My prediction is that we will find rather minor microbiome elements of disease pathogenesis (it is worth looking). However, the integrated genomics aspects of the protocols will be useful for a decade to stimulate discovery.

Name of idea submitter and other team members who worked on this idea ATS Member

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Goal 1: Promote Human Health

Re-examining Antigenicity of Rare Blood Disease Proteins

What specific roles do protein glycosylation and protein complex formation on stable and activated cellular membranes play in inherent immunogenicity and antibody formation to life-saving therapies for rare blood disorders?

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

Details on the impact of addressing this CQ or CC

Inhibitory alloantibody formation to critical life-saving therapies impedes effective replacement therapy in up to 30-40% of children and adults with congenital blood diseases, thereby significantly increasing the complications of the underlying disease. For children with hemophilia A, this treatment complication has significantly limited the impact of the last 20 years of therapeutic advances in product efficacy and safety. Discovery science in this area has focused on the relationship between the immune response and treatment circumstances, and the epitope specificity of the targeted immune response. However, this scientific pathway to discovery has not yielded the critical mechanistic data required to inform effective prevention strategies. Recent advances in our understanding of the co-factors for immunogenicity, the biochemistry of coagulation factor complex formation on cellular membranes, glycobiology and gene transfer must now converge to create a potential platform for exploring new paradigms of immunogenicity, and thus leading to new strategies for inducing tolerance to future new therapeutics in hemophilia.

Feasibility and challenges of addressing this CQ or CC

A recent workshop sponsored by the National Hemophilia Foundation highlighted the threat to novel therapies for hemophilia as well as curative gene therapy from the unsolved problem of replacement protein or gene product antigenicity. However recent advances in our understanding of the co-factors for immunogenicity, the biochemistry of coagulation factor complex formation on cellular membranes, glycobiology and gene transfer, can now converge to create a potential platform for exploring new paradigms of immunogenicity, and thus leading to new strategies for inducing tolerance to future new therapeutic. NHLBI leadership and collaboration with NIAID is needed to bring this combined expertise to bear on the understanding and prevention of this most significant complication of hemophilia therapy.

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

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-20 net votes
6 up votes
26 down votes
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Goal 2: Reduce Human Disease

Rare disease therapeutics high throughput screening

Can we develop model systems for the high throughput screening of new and existing agents as possible therapies for rare diseases?

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 NHLBI Staff

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8 up votes
26 down votes
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