Royal disease: Gene therapy tastes success

Royal disease: Gene therapy tastes success

Haemophilia B: Six patients successfully treated by team led by Indian-origin researcher

A team,led by an Indian-origin researcher,in Britain has successfully treated six patients suffering from the blood-clotting disease known as haemophilia B by injecting them with the correct form of a defective gene,a landmark achievement in the troubled field of gene therapy.

Haemophilia B,carried by Queen Victoria and that affected most European royal houses,is the first well-known disease to appear treatable by gene therapy,a technique with a 20-year record of almost unbroken failure.

The general concept of gene therapy — replacing the defective gene in any genetic disease with the intact version — has long been alluring. But carrying it out in practice,usually by loading the replacement gene onto a virus that introduces it into human cells,has been a struggle.

The success with haemophilia B,reported online Saturday in The New England Journal of Medicine,embodies several minor improvements developed over many years by different groups of researchers.


The delivery virus,carrying a good version of the human gene for the clotting agent known as Factor IX,was prepared by researchers at St Jude Children’s Research Hospital in Memphis. The patients had been recruited and treated with the virus in England by a team led by Dr Amit C Nathwani of University College London; researchers at the Children’s Hospital of Philadelphia monitored their immune reactions.

Haemophilia B is caused by a defect in the gene for Factor IX. Fatal if untreated,the disease occurs almost only in men because the Factor IX gene lies on the X chromosome,of which men have only a single copy.

About one in 30,000 of newborn boys have the disease,with about 3,000 patients in the US.

Dr. Nathwani and his team reported that they treated the patients by infusing the delivery virus into their veins. The virus homes in on the cells of the liver,and the gene it carries then churns out correct copies of Factor IX.

A single injection enabled the patients to produce small amounts of Factor IX,enough that four of the six could stop the usual treatment,injections of Factor IX concentrate prepared from donated blood. The other two patients continued to need concentrate,but less frequently.

After injection,levels of factor IX ranged from two per cent to 12 per cent. Dr Nathwani said patients with 12 per cent of normal factor IX production would no longer be seen in the clinic.

“They would be able to go about their normal daily lives without any problems. The only time that they would have a problem is if they were involved in a road traffic accident or had a big fall from a building site.”

Treating a patient with concentrate costs $300,000 a year,with a possible lifetime cost of $20 million,but the single required injection of the new delivery virus costs just $30,000,Dr Katherine P Ponder of Washington University School of Medicine in St Louis notes in The New England Journal of Medicine,calling the trial “a landmark study.”