Gene therapy has successfully repaired the immune systems of two men who were born with an "incurable" genetic disorder that rendered them almost defenceless against bacterial and fungal infections.
Sixteen months after an operation to repair a defective gene, which each man had inherited from his mother, the once severely ill patients show signs of complete recovery.
The latest success with gene therapy will lead to further operations to treat many other chronic and incurable conditions resulting from the inheritance of defective genes, scientists believe.
Gene therapy involves the alteration of a person's genome to repair or replace a mutated gene. After many 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.
"This a landmark study for chronic granulomatous disorder and the potential of gene therapy. 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.
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 reinserted 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 with a powerful chemotherapy agent designed to rid the body of as many defective phagocytes as possible.
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 in line for gene therapy. 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 charity which has spent £1.2m over the past eight years to promote gene therapy. Liz Nelson, the trust's chief executive, said: "We believe that gene therapy may eventually help many people with genetic disorders, and this early work must be supported."
Adam and Alex Creamer: 'There is real hope now ... it could be a cure'
Chronic granulomatous disorder is caused by a rare genetic fault with a type of white blood cell known as phagocytes, which are the body's frontline defence against bacterial and fungal infections.
Geoff Creamer became aware of the condition when his son Alex was diagnosed with the disorder after being admitted to hopsital with a serious illness. Tests on Mr Creamer's younger son, Adam, showed that he too had a faulty gene on the X chromosome which both boys had inherited from their mother, a healthy carrier.
Unlike girls, who inherit two X chromosomes, boys only inherit one X chromosome which means that any defective genes on the chromosome can result in a manifest disorder because they have no "backup" chromosome.
Mr Creamer, from Chorley, Lancashire, said that throughout their childhood, both boys, who are now 15 and 18, have been highly susceptible to the sort of infections that most children shrug off.
"They do take precautions to avoid infections, for example we don't let them do any gardening," Mr Creamer said.
Alex suffered severe infections before he was properly diagnosed. These became so bad that the family opted for a bone-marrow transplant from a donor. The result is that he now has to take anti-rejection drugs. Adam, however, could benefit from the new approach which would mean transplanting his own genetically altered stem cells back into his bone marrow, with no need for anti-rejection drugs. Mr Creamer said: "There is real hope for Adam now. It would be like a once-only cure for him."
Jeans for Genes helpline 0800 980 4800Reuse content