The boy who is now three was born with rare X-linked severe combined immunodeficiency, (SCID-X1), a condition which only affects males.

It is often called the "baby in the bubble syndrome", and most victims die within their first year without treatment.

The boy was given gene therapy as a baby to save his life and he is the first child in the UK, but the fifth in Europe, to develop leukaemia as a result of the treatment.

Five years ago in Paris 4 of 11 boys given similar gene therapy also developed the disease and one has died.

When the boy started the gene therapy trial in 2005 the doctors at Great Ormond Street were aware of the leukaemia risk.

But as Professor Bobby Gaspar, a consultant immunologist working on the programme says, the benefits for such children outweigh the risks as their only other option is a bone marrow transplant.

However unless a relative is a perfect match, they also have to undergo chemotherapy, which kills up to 20% of such babies.

Professor Gaspar says they knew that this was a possible side-effect and therefore carefully counselled families before they entered the programme.

Gaspar says such risks had to be balanced against the risks of conventional treatment which contain significant hazards.

Scientists believe a vector, a modified virus introduced to the bone marrow cells to deliver a working copy of the defective gene, is the cause of the problem.

As they are unable to control where it ends up, they suspect that if it lands next to a cancer gene it can switch it on, causing cancer.

They are now planning another trial using a vector that has been modified so that even if it lands next to a cancer gene it will not switch it on.

While childhood leukemia is as a rule treatable, with cure rates of 90 percent or more, children with SCID who cannot get a bone marrow transplant almost always die within a year.

To test the effects of permanent CnA 1 expression Enrique Lara-Pezzi from Rosenthal's lab overexpessed CnA 1 in muscle cells, and observed increased proliferation of muscle stem cells. Switching off the protein had the opposite effect; stem cells stopped dividing and differentiated into muscle cells instead. When CnA 1 was overexpressed in the muscles of transgenic mice, the animals were resistant to the destructive effects of muscle injury and regenerated the damage more efficiently.

Using sophisticated molecular techniques the scientists revealed that calcineurin accomplishes its effect on muscle by inhibiting another protein called FoxO. FoxO is a transcription factor, a protein that plays a crucial role in skeletal muscle atrophy through the induction of genes involved in cell cycle repression and protein degradation. Suppressing the effects of FoxO, calcineurin ensures that proliferating cells stay alive and keep dividing to produce enough cells to repair muscle damage.

Supplementary CnA 1 also reduces the formation of scars in damaged muscle, helps speed up the resolution of inflammation and protects muscle cells from atrophy under starvation, says Rosenthal. These effects make CnA 1 a promising candidate for new therapeutic approaches against muscle wasting.

embl/

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