New Method for Controlling Bleeding in Hemophiliacs

A new study describes how a gene-modified bone marrow transplant can be used to initiate clotting in hemophiliacs that lack Factor 8 (FVIII) by having the missing clotting factor packaged in their own platelets.

Researchers at the Children's Research Institute (Milwaukee, WI, USA), the Wisconsin BloodCenter Blood Research Institute (Milwaukee, USA), and the Medical College of Wisconsin (MCW, Milwaukee, USA generated a line of transgenic mice that express FVIII only in platelets, using the platelet-specific alphaIIb promoter. They then bred this transgene into mice missing FVIII. Bone marrow (BM) from heterozygous transgenic mice was then transplanted into immunized FVIII mice after a lethal or sublethal dose of irradiation. The study results showed that after BM reconstitution, 85% of the recipients survived tail clipping when an 1100-centigray (cGy) dose regimen was used, 85.7% of recipients survived when a 660-cGy dose regimen was used, and 60% of the recipients survived when the mice were conditioned with a 440-cGy dose. Further studies showed that transplantation with only 1% to 5% of heterozygous BM cells still improved hemostasis in the mice with hemophilia. The study was published in the October 2008 edition of Blood.

"These results demonstrate that the presence of FVIII-specific immunity in recipients does not negate engraftment of 2bF8 genetically modified hematopoietic stem cells, and transplantation of these hematopoietic stem cells can efficiently restore hemostasis to hemophilic mice with preexisting inhibitory antibodies,” concluded lead author Qizen Shi, Ph.D., M.D., of the department of pediatrics at MCW, and colleagues.

The researchers estimate that this type of approach could help the 30-35% of hemophilia patients that have developed inhibitory antibodies against the missing clotting protein. The bone marrow would be removed from the patient and the stem cells treated with Factor VIII, which is placed in the platelets. The marrow is returned to the patient, who then retains the essential clotting mechanisms to stop bleeding that otherwise would lead to complications. For people suffering from hemophilia, the results of this study provide hope that they could potentially lead a disease-free life.

Related Links:
Children's Research Institute
Wisconsin BloodCenter Blood Research Institute
Medical College of Wisconsin