Expert Reviews in Molecular Medicine

 



Review Article

Pathophysiology and therapy for haemoglobinopathies; Part I: sickle cell disease


Catherine Madigan a1 and Punam Malik a2c1
a1 Hematology/Oncology, Childrens Hospital Los Angeles, Mail Stop 54, 4650 Sunset Boulevard, Los Angeles, CA 90027, USA.
a2 Keck School of Medicine, University of Southern California; Attending Physician, Hematology-Oncology, Childrens Hospital Los Angeles, Mail Stop 54, 4650 Sunset Boulevard, Los Angeles, CA 90027, USA.

Abstract

In sickle cell disease, a single base pair substitution in the gene encoding the β-globin chain of the haemoglobin molecule gives rise to a surprisingly broad spectrum of pathophysiological and clinical manifestations. Inflammation, endothelial activation, red blood cell membrane abnormalities and altered availability of vasoactive factors characterise this disorder. Clinically, patients suffer from a host of seemingly unrelated maladies, from pain episodes to strokes, life-threatening infections and pulmonary hypertension. Deepened understanding of this complex disease now allows us to begin to turn away from simple supportive treatments, and move towards therapies aimed at specific pathophysiological targets. This article, the first of two reviews on the pathophysiology of haemoglobinopathies, discusses the molecular basis of sickle cell disease, and elaborates on the many factors that exacerbate or ameliorate the disease process. It then focuses on the promising targeted therapies currently in use or under investigation. An accompanying article on haemoglobinopathies (Part II) focuses on thalassaemias.


Key Words: Sickle cell anaemia; thalassaemia; molecular basis; pathophysiology; therapeutic strategies.

Correspondence:
c1 Keck School of Medicine, University of Southern California; Attending Physician, Hematology-Oncology, Childrens Hospital Los Angeles, Mail Stop 54, 4650 Sunset Boulevard, Los Angeles, CA 90027, USA. Tel: +1 323 669 5438; Fax: +1 323 913 3087; E-mail: pmalik@chla.usc.edu