Paroxysmal nocturnal hemoglobinuria, or PNH, is a chronic disease where a a portion of a patient's oxygen-carrying red blood cells are missing the normally present complement inhibitors and are therefore abnormally fragile and inadvertently destroyed by normal complement activation. PNH is caused by a mutation in certain types of adult blood cells. Because of this mutation, certain types of proteins, including complement inhibitors, are unable to attach to the surface of the cell,as is normally the case. More specifically, the PNH mutation prevents the assembly of a fatty tail, known as a glycosyl-phosphatidylinositol (GPI) anchor, a necessary step in surface attachment of some proteins.

Consequently, proteins with this GPI anchor are diminished or absent, two of which are crucial in protecting blood cells from inappropriate complement destruction. Without these two protective proteins, PNH red blood cells, in particular, are easily burst by complement, resulting in low red blood cell count (anemia), fatigue, bouts of dark colored urine and various other complications. PNH is frequently associated with other types of blood cell production diseases including aplastic anemia and other forms of bone marrow failure

Alexion's anti-C5 therapy in the treatment of PNH

Alexion's eculizumab is a protein based drug that specifically blocks cleavage of the C5 component of the complement system, thereby preventing the final stages of complement activation. In laboratory tests, eculizumab completely blocked complement-mediated red blood cell destruction. As a result, it is possible that treatment with eculizumab could block the complement-mediated destruction of PNH red blood cells. Eculizumab is currently being studied to see if it has the potential to improve the quality of life through reduction in disease symptoms.

In February 2004, Alexion reported in the New England Journal of Medicine (February 5th issue; volume 350, pages 552-559) the results from its open-label Phase II clinical trial evaluating the use of eculizumab in 11 paroxysmal nocturnal hemoglobinuria (PNH) patients at two clinical sites in the United Kingdom.

To receive a paper reprint of the New England Journal of Medicine article or to inquire about Alexion's program in PNH please contact us . If you are interested in learning more about the PNH registry please click here.

To learn more about PNH and aplastic anemia, please contact the Aplastic Anemia & MDS International Foundation, Inc, at www.aamds.org or a review of PNH by the AA&MDS foundation.