'Incurable' illness falls to gene therapy

By Steve Connor

Gene therapy has repaired the immune systems of two men who were born with an "incurable" genetic disorder that made them almost defenceless against bacterial and fungal infections.

Sixteen months after an operation to repair a defective gene, the once severely ill patients show signs of complete recovery.

Scientists believe the latest success will lead to further operations to treat many other chronic and incurable conditions resulting from the inheritance of defective genes.

Gene therapy involves altering a person's genome to repair or replace a mutated gene. After years of hype and hope, the technique seems finally to have proven its potential with a handful of successful operations.

The latest success was achieved by doctors in Germany, Switzerland and Britain who treated two men with chronic granulomatous disorder (CGD), an immunodeficiency disease caused by a defective gene on the maternally inherited X chromosome.

The men - both in their mid-twenties - suffered repeated life-threatening infections from bacteria and fungi and from an early age had to rely on powerful antibiotics and antifungal medicines. Since their operations 16 months ago at the University Hospital in Frankfurt, both patients have gained weight and have been free of the severe infections that have plagued them since childhood.

Manual Grez of the Institute for Biomedical Research in Frankfurt, one of the leaders of the study published in the journal Nature Medicine, said the results suggest that it may be possible to use gene therapy to treat other similar inherited diseases.

"These are very positive results but there is still a lot of work needed to make this technology available to all CGD patients," Dr Grez said, adding that the work was a "landmark study".

CGD is rare, affecting about 1 in 250,000 people in Britain, and is caused by defects in a type of white blood cell known as phagocytes, which normally engulf and destroy harmful microbes as they invade the body.

About 60 per cent of CGD sufferers inherit a defective copy of the gp91phox gene which leaves their bone marrow unable to manufacture phagocytes with the right chemical machinery for destroying the microbes.

To repair the problem, the doctors removed stem cells from the patients' bone marrow, inserted a healthy copy of the gp91phox gene into the cells while culturing them in the laboratory, and then inserted the engineered cells into the patients' bone marrow.

To increase the chances of the genetically altered stem cells repopulating the bone marrow, the doctors partially destroyed the patients' own bone marrow.

Professor Adrian Thrasher of the Great Ormond Street Hospital in London, who has performed similar gene therapy operations involving other cells of the immune system, said British CGD patients could be next.

"Further improvements and refinements in the technology are now under way to maximise the effectiveness and safety of the system," he said. "This is a step towards the definitive cure of CGD but there is still a lot of work to be done,"

The work was carried out with the help of the CGD Research Trust which has spent £1.2 million ($3.4 million) over the past eight years to promote gene therapy. Liz Nelson, the chief executive, said: "We believe gene therapy may eventually help many people with genetic disorders, and this early work must be supported."

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