Gene therapy can chalk up its second success. Two children with a defective immune system and metabolic problems have been cured by replacing their defective gene with a healthy one. The results, which appear in the 28 June issue of Science, suggest gene therapy techniques that can be applied to other blood diseases as well.
Severe combined immunodeficiency, or SCID, is a rare group of conditions in which a person's immune system doesn't develop properly and common infections, such as chicken pox, can prove fatal. In the first successful genetic modification of an inherited disease, French doctors repaired the immune systems of two babies with SCID-X1 in 2000 (ScienceNOW, 28 April). Seven other afflicted children have been cured since then.
The newly treated patients have a more severe form, ADA-SCID, which makes up 15% to 30% of SCID cases. These children can't make the enzyme adenine deaminase (ADA), a lack that wipes out more of the immune system than in SCID-X1 and causes a host of metabolic problems, such as enlarged livers and diarrhea. Previous attempts at gene therapy replaced the damaged ADA gene in some circulating immune cells, but the cells didn't make enough enzyme.
In the current study, the researchers removed stem cells, the progenitors of many blood cell types, from the bone marrow of a 7-month old and a toddler in Israel. The team inserted the corrected ADA gene in culture and injected the modified stem cells 4 days later. But first, the team had partially obliterated the children's marrow with chemotherapy. The bone marrow responds by cranking up its stem cell production, and the genetically modified cells receive the same push, says gene therapist Claudio Bordignon, lead researcher for the team at the San Raffaele Telethon Institute for Gene Therapy in Milan, Italy.
Several months later, both patients had high levels of healthy immune and other blood cells. The children made normal amounts of ADA, which reduced toxic metabolites in their bloodstreams, and when they were vaccinated against tetanus, they made antibodies to the injected toxin, indicating that the treatment had fully repaired the immune system.
According to pediatrician Donald Kohn of Children's Hospital in Los Angeles, the results are very encouraging for gene therapy. The technique's success with SCID is "almost to the point where we can talk to insurance companies about making it a reimbursable procedure," he says. More important, though, he says the addition of the chemotherapeutic step suggests the method can help a variety of blood diseases, such as anemias.