The findings of the six-person study mark the first proof that gene therapy can reduce disabling, painful bleeding episodes in patients with the inherited blood disorder. Four study participants stopped receiving protein injections to prevent bleeding episodes after undergoing the therapy and have not suffered spontaneous bleeding. Several have also participated in marathons and other activities that would have been difficult prior to gene therapy. The study volunteers were all treated at the Royal Free Hospital in London under the care of Doctor Edward G.D. Tuddenham.
"This is a potentially life-changing treatment for patients with this disease and an important milestone for the field of gene therapy. It could have ramifications for the treatment of haemophilia A, other protein and liver disorders and chronic diseases such as cystic fibrosis," said Doctor Amit Nathwani.
Haemophilia B is caused by an inherited mistake in the gene for making a protein called Factor IX, which is essential for normal blood clotting. The gene is carried on the X chromosome. As a result, haemophilia B is almost exclusively a disease of men. About 1 in 30,000 individuals inherit the mutation.
For this study, each patient received a one-time infusion of the vector into a vein in the arm. Two patients each were treated with escalating doses of the vector. Following treatment, Factor IX levels rose in all six patients from less than 1 per cent of normal levels prior to the gene therapy to between 2 and 12 per cent.
Factor IX levels increased the most in the two study volunteers who received the highest dose of the experimental vector, researchers said. After treatment, levels of the protein ranged from 3 to 12 per cent in those men. Even modest increases that raise Factor IX production to more than 1 per cent of normal levels have the potential to dramatically affect a patient's quality of life and reduce bleeding episodes, said Doctor Andrew Davidoff.
One of the participants who received the highest dose of the vector underwent successful, short-term steroid treatment after his liver enzymes rose slightly after the vector infusion. The rise signalled mild liver damage. The volunteer remained otherwise healthy, his Factor IX levels remain above pre-infusion levels and his liver enzymes have returned to normal. Liver enzymes also rose slightly, but remained in the normal range, for the other participant who received the highest dose of the vector. That participant also received a short course of steroids.
Researchers believe an immune response targeting the vector triggered the elevated enzyme levels. A similar response was reported in earlier gene therapy trials conducted by other investigators using a different vector
MEDICA.de; Source: St. Jude Children's Research Hospital