Advances in experimental treatment of beta-thalassaemia

Expert Opinion on Investigational Drugs
G P Rodgers, Y Saunthararajah

Abstract

Beta-thalassaemia is highly prevalent and world wide in its distribution. The gene to modify the clinical course of patients with transfusion-dependent thalassaemia (thalassaemia major), the gamma-globin gene, is already present in these patients but silenced in the course of development. During erythropoiesis, progenitors are believed to go through a phase where the milieu favours gamma-globin production. One pharmacological strategy to increase gamma-globin production is directed at recruiting such early progenitors through the use of cytotoxic agents (+/- erythropoietin) that presumably deplete more mature progenitors. Another promising strategy is to use chromatin-modifying agents that prevent the silencing of the gamma-globin gene that occurs during development. These agents, the methyl-transferase inhibitors and histone deacetylase inhibitors, either alone or in combination, may be able to produce the robust increase in gamma-globin and hence fetal haemoglobin and total haemoglobin, needed to successfully treat thalassaemia major. Studies of these agents, which are already available for clinical trials, should be encouraged.

References

Jul 1, 1985·Molecular and Cellular Biology·W L HsiaoI B Weinstein
Mar 1, 1985·Proceedings of the National Academy of Sciences of the United States of America·R JaenischK Harbers
Apr 23, 1987·The New England Journal of Medicine·G LucarelliG Aureli
Jun 20, 1985·The New England Journal of Medicine·L WolfeD G Nathan
Jul 31, 1982·Lancet·E D ThomasR Storb
Jul 1, 1982·Proceedings of the National Academy of Sciences of the United States of America·J DeSimoneD Zwiers
Dec 9, 1982·The New England Journal of Medicine·T J LeyA W Nienhuis
Dec 1, 1984·Carcinogenesis·B I CarrA Riggs
Dec 1, 1983·Archives of Disease in Childhood·B Modell, M Petrou
Feb 1, 1995·Molecular and Cellular Biology·G ZitnikT Papayannopoulou
Apr 21, 1995·Cell·P W LairdR Jaenisch
Jul 18, 1995·Proceedings of the National Academy of Sciences of the United States of America·M SadelainR C Mulligan
Jan 14, 1993·The New England Journal of Medicine·S P PerrineN F Olivieri
Sep 16, 1993·The New England Journal of Medicine·C H Lowrey, A W Nienhuis
Jun 15, 1995·The New England Journal of Medicine·G D SherN F Olivieri
Nov 12, 1996·Proceedings of the National Academy of Sciences of the United States of America·S J Darkin-RattrayD M Schmatz
Apr 29, 1997·Proceedings of the National Academy of Sciences of the United States of America·L Jackson-GrusbyR Jaenisch
Aug 16, 1997·Lancet·N F OlivieriD J Weatherall
Jul 21, 1998·Annals of the New York Academy of Sciences·G J Dover
Jul 21, 1998·Annals of the New York Academy of Sciences·E A Rachmilewitz, M Aker
Jun 29, 2000·Baillière's Clinical Haematology·L F Bernini, C L Harteveld
Dec 29, 2000·Journal of Pediatric Hematology/oncology·S T SingerE P Vichinsky
Jan 5, 2001·Expert Opinion on Investigational Drugs·D R Richardson

❮ Previous
Next ❯

Citations

May 24, 2011·Journal of Pediatric Hematology/oncology·Saqib H AnsariTabassum Mehboob
Jan 22, 2005·Annual Review of Medicine·Stanley L Schrier, Emanuele Angelucci
Sep 11, 2002·American Journal of Hematology·O WittA Pekrun
Oct 7, 2004·Biochemical and Biophysical Research Communications·Xinsheng NanA Christopher Boyd
Nov 10, 2004·Seminars in Hematology·Yogen Saunthararajah, Joseph DeSimone
Aug 26, 2004·British Journal of Haematology·Yogen SaunthararajahJoseph DeSimone

❮ Previous
Next ❯

Related Concepts

Related Feeds

Anemia

Anemia develops when your blood lacks enough healthy red blood cells. Anemia of inflammation (AI, also called anemia of chronic disease) is a common, typically normocytic, normochromic anemia that is caused by an underlying inflammatory disease. Here is the latest research on anemia.