ERYTHROTHERAPY · DEFINING NEW DRUGS AND DRUG TARGETS FOR TREATMENT OF ANEMIA
7РП — „Хора“ (Действия „Мария Кюри“)
- Период
- 2012-04-01 → 2016-03-31
- Финансиране от ЕС
- 100 000 €
- Участници
- 1
- Схема
- MC-CIG
Линиите свързват координатора с партньорите.
Накратко на български
Механизмите за превръщане на фибробласти в червени кръвни клетки и нови лекарствени мишени за анемия на Даймонд-Блакфан се анализират в проекта. Това помага за разработването на специфични терапии за хора с тежки форми на анемия, за които в момента няма ефективно лечение.
Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.
Резултати накратко
DEFINING NEW DRUGS AND DRUG TARGETS FOR TREATMENT OF ANEMIA
NEW ANEMIA RESEARCH TOOLS AND THERAPIES BASED ON DECODING RED BLOOD CELL DEVELOPMENT AND DISEASE Two billion people suffer from red blood cell deficiency or anemia, a debilitating condition often caused by failure to produce red blood cells. Today there is no effective therapy for many types of anemia, including aplastic anemias such as Diamond-Blackfan anemia (DBA). In this project we developed fundamentally new concepts for treating anemic patients that today lack effective treatment. RESULT 1. DEFINEE THE MECHANISMS REGULATING RED BLOOD CELL FATE THROUGH DIRECT REPROGRAMMING. Through a reductionist approach my team identified 4 factors that are able to directly reprogram fibroblasts to erythroid cells. The results were published in Cell Reports in 2016 My research group will now continue this work studying the mechanisms of direct erythroid reprogramming in order to understand essential molecular events involved in determining erythroid fate. Our system will further be used to model congenital anemia and opens a door for developing cell therapy-based anemia treatment. In addition, this approach reduces the need to perform developmental research on animals. RESULT 2. DISCOVERY OF NOVEL DRUG CANDIDATES FOR DIAMOND-BLACKFAN ANEMIA (DBA). DBA is a congenital hypoplastic anemia and no drugs are available to correct the underlying problem, leaving patients with severely reduced life quality and life expectancy. Based on successful screening results we identified a promising drug target as well as a group of promising drug candidates for DBA (unpublished findings). Our exclusive results represent the first step towards developing disease-specific drugs.
Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз
Цел на проекта
More than a billion people suffer from anemia. The only drug used to symptomatically increase red blood cell production in anemic patients is recombinant erythropoietin (Epo). While Epo injections effectively promote red blood cell production in patients suffering low endogenous Epo production, aplastic anemia and anemia associated with cancer, inflammation and infection do not respond well to recombinant Epo treatment.Aim A: Since there is a great need for new drugs that can treat Epo-resistant anemias the first aim of ERYTHROTHERAPY is to identify novel drug target for production of Epo-responsive cells. Using next-generation mRNA sequencing we identified 250 candidate genes that have the potential to be targeted by drugs and are highly expressed in red blood cell progenitor cells. RNA interference based screening strategies will be used to systematically characterize which if these genes can be targeted to promote red blood cell progenitor proliferation. If successful this study will lead to development of a novel class of erythropoiesis stimulating agents able to manage conditions that today lack pharmacological treatment.Aim B: The second goal of this project is to identify mechanism-based treatment strategies for Diamond-Blackfan anemia (DBA; OMIM #105650). All known DBA disease genes encode for ribosomal protein (RP) genes. Despite the recent advances in DBA genetics the pathophysiology remains elusive, which until now has prevented development of disease-specific therapies.In order to develop effective and specific DBA drugs the ERYTHROTHRAPY proposal uses an animal model for DBA to identify the molecular mechanisms linking RP-deficiency to anemia and bone marrow failure. Since limitations of previous mouse models for DBA make them unsuitable for this research strategy we generated a novel RP-deficient DBA mouse by taking advantage of Doxycycline-regulatable RNA interference. The drug-inducible strategy allows reversible and dose-dependent downregula""
Оригинален текст от CORDIS (на английски).
Участници
- MAX IV Laboratory, Lund University · LUNDКоординаторШвеция
Връзки
Данни: CORDIS, © Европейски съюз