Here is how it might work. Suppose your child is born with an incurable disease due to a mutated gene. After diagnosis, the cure would go like this: Step 1: hair, blood or skin cells are collected from the patient and allowed to replicate. This is a standard laboratory procedure. Step 2: the mutated genes in cells in the sample are replaced with corresponding normal genes. This step involves using techniques from the field of gene therapy. Several possible methods are being researched for deleting and introducing new genes. Step 3: the cells are reprogrammed to create induced pluripotent cells, iPS cells that for all practical purposes are like patient-specific embryonic stem cells. Reprogramming of any cells to pluripotent state, was discussed in a previous post on this blog, Rebooting cells and longevity. The resulting iPS cells are functionally equivalent to the patient’s original stem cells, but no longer have the genetic defect. They can differentiate into any cell type given the correct signaling conditions. Step 4: The iPS cells are introduced back into the body in such a way as to regenerate organs free of the disease. For example, if an organ such as the heart has been damaged by the disease, the iPS cells could be introduced so as to regenerate healthy heart tissue. While some success has been achieved with mice, Step 4 will require significant disease-related research if it is to be used in humans. Introducing iPS cells into a live organism can lead to tumors such as teratomas if the signaling conditions are not correct.
Research reported a few days ago shows that for one human genetic disease, Fanconi anemia (FA), steps 1-3 have been successful. “FA is characterized by short stature, skeletal anomalies, increased incidence of solid tumors and leukemias, bone marrow failure (aplastic anemia), and cellular sensitivity to DNA damaging agents such as mitomycin C(ref).” “Caused by mutations in one of 13 Fanconi anemia (FA) genes, the disease often leads to bone marrow failure, leukemia, and other cancers(ref).”
The researchers started by collecting hair and skin cells from FA patients, and they ended up producing patient-specific iPS cells that were cured of FA. Since blood cells are some of the worst affected by FA, they “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(ref)” The researchers have set their sights on going forward to achieve Step 4.
The prospect is for a simple and elegant approach to treating many, perhaps most, genetic diseases.