Combined approach cures human genetic disease in vitro

La Jolla, CA — Researchers have proved in principle that a human genetic disease can be cured using a combination of gene therapy and induced pluripotent stem (iPS) cell technology.

The study is a major milestone on the path from the laboratory to the clinic. Although studies have demonstrated the efficacy of the approach in mice, it had never been achieved in humans. The Salk study offers the first proof that this technology can work in human cells.

“The hope in the field has always been that we’ll be able to correct a disease genetically and then make iPS cells that differentiate into the type of tissue where the disease is manifested and bring it to clinic, “said the study’s leader Professor Juan-Carlos Izpisua Belmonte, director of the Center of Regenerative Medicine in Barcelona, Spain.

Belmonte’s team focused on Fanconi anaemia (FA), a genetic disorder responsible for a series of hematological abnormalities that impair the body’s ability to fight infection, deliver oxygen, and clot blood. Caused by mutations in one of 13 FA genes, the disease often leads to bone marrow failure, leukemia, and other cancers.

After taking hair or skin cells from patients with Fanconi anemia, the investigators corrected the defective gene in the patients’ cells. They then successfully reprogrammed the repaired cells into iPS cells. The resulting FA-iPS cells were indistinguishable from human embryonic stem cells and iPS cells generated from healthy donors.

The researchers then tested whether patient-specific iPS cells could be used as a source for transplantable hematopoietic stem cells. They found that FA-iPS cells readily differentiated into hematopoietic progenitor cells primed to differentiate into healthy blood cells.

“We haven’t cured a human being, but we have cured a cell,” Belmonte explains. “In theory we could transplant it into a human and cure the disease.”

Although hurdles still loom before that theory can become practice — in particular, preventing the reprogrammed cells from inducing tumors — in coming months Belmonte and Verma will be exploring ways to overcome that and other obstacles.

The research is published in Nature.