GENE therapy has cured Welsh baby Rhys Evans of the fatal 鈥渂ubble boy鈥� disease. 鈥淗is progress seems nothing short of a miracle,鈥� says his mother Marie. Another boy treated more recently continues to improve.
The treatment, carried out at London鈥檚 Great Ormond Street Hospital, is one of only a handful of successful gene therapy trials in people. It is also only the third trial of gene therapy for severe combined immunodeficiency or SCID. Alain Fischer鈥檚 team at the Necker Hospital in Paris reported the first-ever treatment in 2000, of two boys, while an Italian-Israeli team recently reported promising initial results with two people who have another form of the disease.
Nine people in total have had gene therapy at the Necker Hospital, and seven of them are doing well. But the researchers at Great Ormond Street think they have developed a better way of delivering the gene to correct the fault that causes the disease.
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The type of SCID that the Welsh baby had is 鈥淴-linked鈥�, caused by a fault in a gene on the X chromosome that makes an immune protein called interleukin-2. The disease affects boys because they only have one X chromosome.
The faulty gene stops the development of T cells, a key part of the immune system. Children must be kept in isolation to protect them from catching infections and usually die young. A bone marrow transplant can cure the disease, but suitable donors are only found in a third of cases.
To treat the boys, the Great Ormond Street team took the stem cells that give rise to immune cells from the two boys鈥� bone marrow. Then they used a modified form of a retrovirus found in gibbons to add a normal copy of the faulty gene to the stem cells. The virus has altered spikes on its surface which may mean it binds better to stem cells and transfers the gene to them more efficiently, team leader Adrian Thrasher told New 杏吧原创.
The engineered stem cells were then returned to the boys鈥� bodies. Rhys Evans is now back at home, with normal T cell levels, seven months after treatment. The second child, treated just three months ago, continues to improve at home.
The Great Ormond Street researchers say they are planning to treat another four boys over the next two years. They are also treating a child with another immune deficiency, X-linked chronic granulomatous disease. In this disease T cells are present but don鈥檛 work properly. To make room for new cells, the child鈥檚 bone marrow will have to be partly destroyed by chemotherapy before the altered stem cells are put back.
While gene therapy is at last starting to live up to its promise, there鈥檚 still a long way to go before many other inherited diseases can be treated. Getting genes into cells that can be removed from the body and putting them back is relatively easy. But diseases that affect organs such as the kidney can鈥檛 be treated this way. Getting genes into enough cells inside the body, and controlling their expression, remains the big challenge.