Gene therapy hope for haemophilia

Scientists have successfully used gene therapy to prevent bleeding in a small trial of patients with the inherited blood disorder haemophilia B.

A one-time treatment of the therapy was sufficient to safely produce sustained levels of a critical blood clotting factor up to one year later, alleviating the need for further medical intervention.

'This is a major milestone in the quest to cure the bleeding disorder,' said co-author Professor John Rasko, at the Royal Prince Alfred Hospital, Sydney, Australia. 'Those people in the trial have previously had to live with the risks of spontaneous bleeding every day.'

Haemophilia B affects around one in 30,000 boys and men and is caused by a deficiency of the factor IX blood clotting factor. Patients rely on regular clotting factor infusions as often as three times a week to prevent debilitating bleeding episodes.

In the phase 1/2 clinical trial, funded by Spark Therapeutics and Pfizer, researchers at the Royal Prince Alfred Hospital injected ten men with a modified version of the factor IX gene that codes for a clotting factor that is 8-12 times stronger than the normal factor.

Prior to the trial, all ten participants had factor levels less than 2 percent of the normal value. After one infusion of the gene therapy, all produced sustained levels of clotting factor of approximately 30 percent, up to 18 months after the treatment. Nine of the ten patients had no bleeds over the one-year follow-up period and eight of the ten did not require any further standard treatments. None of the patients experienced serious side effects.

'It's definitely the best thing I've seen so far in terms of consistency of responses in patients, in terms of minimal side effects, in terms of overall efficacy,' Dr Thierry VandenDriessche at the Free University of Brussels in Belgium, who was not involved in the research, told Genetic Engineering & Biotechnology News.

Professor Rasko said that the therapy could be 'life-changing' but added that it was still early days. Long-term follow-up will determine whether the effect will last beyond the 18 months of the trial.

According to co-author Dr Lindsey George of Children's Hospital of Philadelphia, Pennsylvania, the researchers plan to continue the development of the therapy in a Phase 3 trial. 'I am optimistic this study is just the beginning of a true paradigm shift in the treatment of haemophilia,' she concluded.

The results of the clinical trial are published in The New England Journal of Medicine.