Showing 5 ideas for tag "thalassemia"

Goal 3: Advance Translational Research

Genome Editing and Gene Therapy

There is a critical need for the establishment of strategies that will determine the efficacy, safety, and toxicity of genome editing techniques specifically in hematologic diseases.

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

Details on the impact of addressing this CQ or CC

Inherited monogenic hematologic diseases such as hemophilia, beta-thalassemia and sickle cell disease are prime targets for future application of genome editing technology. However, studies are still needed to advance our understanding of the biology of genome editing as well as determine which other disorders are amenable to genome editing correction. Emphasis on preclinical research that focuses on determining the accuracy, safety and efficiency of this technology in order to help minimize off-target mutations and reduce toxicity, is essential for effective translation of this technology into the clinic. Once preclinical efficacy is established, support will be needed for clinical vector production, toxicity testing of the vectors/reagents used, and the performance of clinical trials. The gene correction strategies developed for inherited disorders will also be attractive for other hematologic diseases, and autoimmune disorders like lupus, rheumatoid arthritis, and type I diabetes). There is also a critical need for supporting preclinical validation studies, scale-up and GMP cell manufacturing, all of which could be shared infrastructures across multiple diseases in the NHLBI portfolio.

Name of idea submitter and other team members who worked on this idea Alice Kuaban on behalf of the American Society of Hematology (ASH)

Voting

69 net votes
87 up votes
18 down votes
Active

Goal 2: Reduce Human Disease

Combination Iron Chelator Trials in Thalassemia and other transfusion-dependent anemias

Three chelators are presently available in the US and much of the world: parenteral deferoxamine, and oral deferasirox, as well as oral deferiprone. Monotherapy is unsuccessful in a significant minority of patients, due to side effects or inadequate response at tolerable doses. Taking a page from enormously successful strategies for combination oral therapy in hypertension, led by NHLBI and others over the past four... more »

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

Feasibility and challenges of addressing this CQ or CC

NHLBI should lead the way for these trials, which will be of enormous benefit to reduce morbidity and mortality in thalassemia, a terribly common problem worldwide, as well as in the rare, transfusion-dependent congenital anemia.

Voting

39 net votes
54 up votes
15 down votes
Active

Goal 2: Reduce Human Disease

Iron Metabolism in thalassemia syndromes, and other rare and common anemias

Thanks to elegant work since the 1990s, many details of the role of iron regulation and metabolism have been elucidated. Recent efforts in academic and pharmaceutical laboratories aim to translate these discoveries into therapies that may alleviate anemia in iron-refractory states (including anemia of inflammation and congenital disorders), and may have important therapeutic effects in non-transfusion-dependent thalassemia,... more »

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

Voting

40 net votes
55 up votes
15 down votes
Active

Goal 1: Promote Human Health

Continued focus on mechanism of Red Cell Production

Recent murine studies and early phase clinical trials demonstrate that pharmacologic “traps” for TGF-beta family members may stimulate erythropoiesis in non-erythropoietin-dependent mechanisms. The molecular details of this process remain to be elucidated. Better understanding of this process, which may markedly decrease the marrow problem of “ineffective erythropoiesis,” may lead to improved therapies in thalassemia,... more »

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

Voting

47 net votes
57 up votes
10 down votes
Active

Goal 2: Reduce Human Disease

Identifying Chronic Pain and exploring the onset and severity among patients with thalassemia

While the primary pathophysiology of thalassemia is related to globin gene mutations and unbalanced globin chain expression, the downstream consequences are manifold. Chronic pain turns out to be one of the most important factors identified by patients with transfusion dependent thalassemia major in health-related quality of life surveys and patient-reported outcome measures. Even as therapies aimed and gene editing,... more »

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

Voting

37 net votes
47 up votes
10 down votes
Active