Researchers at the Salk Institute for Biological Studies have provided the first proof in principle that a genetic disease in humans can be cured with combined stem cell-gene therapy. The research team focused on a genetic disorder called Fanconi anemia (FA), which causes hematological abnormalities that interfere with the body’s ability to fight infection, deliver oxygen, and clot blood. The disorder is caused by mutations in one of 13 FA genes, and even following bone marrow transplants to deal with the hematological problems, patients remain at high-risk for cancer and other serious problems. The researchers took hair or skin cells from patients with FA and corrected the defective gene in the patients’ cells using gene therapy techniques pioneered at Salk. They then successfully reprogrammed the repaired cells into induced pluripotent stem (iPS) cells using a combination of transcription factors, OCT4, SOX2, KLF4 and cMYC. 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 transplant-able hematopoietic stem cells, and 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,” study leader Juan-Carlos Izpisua Belmonte, PhD, 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 the research team will be exploring ways to overcome that and other obstacles. In April 2009, they received $6.6 million from the California Institute Regenerative Medicine to pursue research aimed at translating basic science into clinical cures. “If we can demonstrate that a combined iPS–gene therapy approach works in humans, then there is no limit to what we can do,” says Inder Verma, PhD, a Salk colleague.
(Source: Science Daily, June 1, 2009)
