'Bubble boy' progress reported

From left: Tushar Menon, Inder Verma and Amy Firth. Salk Institute

From left: Tushar Menon, Inder Verma and Amy Firth. / Salk Institute

Those born with the immune disorder SCID-X1, or "bubble boy disease" may one day benefit from a new treatment to give them a functioning immune system, if new research from the Salk Institute succeeds.

Working with cultures of induced pluripotent stem cells from a patient, Salk scientists led by gene therapy expert Inder Verma repaired the genetic defect that causes the disease. Infants born with this inherited condition have virtually no immune resistance, and can be killed by infections easily defeated by normal immune systems.

Researchers were able to generate what appear to be mature NK, or "natural killer" immune cells, the first time this has been done. They also generated progenitors of T cells. This doesn't repair all the immune system, but it's a big step in that direction.

These preliminary results may pave the way to an alternative from treating these patients, Verma said. At present, patients can be treated with bone marrow transplants, but matching donors are hard to find. Gene therapy using a viral vector to repair the defect has been successful, but has caused leukemia in some patients when the corrective gene went into the wrong place. Newer forms of this therapy appear to have reduced the risk, but long-term followups of those treated are still in progress.

Salk researchers dispensed with viruses entirely by using the TALEN technology, which allows genetic editing without viruses, and is also more precise.

The study was published in the journal Cell Stem Cell on March 12. Tushar Menon and Amy L. Firth are the first authors. Verma is the senior author.

SCID-X1 is caused by an inactivating mutation on a gene called IL-2Rg located on the X chromosome, which means it exclusively affects males. (For females who carry the mutation on one chromosome, the functional gene on the other chromosome suffices).

One-letter mutation

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'Bubble boy' progress reported