Genetic mutations in one’s own stem cells can be corrected before transplantation
April 11, 2010 - One of the most important goals of therapy for retinal degeneration is to reverse existing vision loss. The Foundation Fighting Blindness currently funds several groups of scientists exploring the use of stem cells to replace lost photoreceptors in visually impaired eyes.
There are several approaches to stem cell research, as outlined in our stem cell research fact sheet. One involves the use of normal adult cells, from the skin or other tissues, which are reprogrammed to become stem cells. These “induced pluripotent cells” (ipSCs) have both advantages and disadvantages (hear more about induced pluripotent stem cells and the various other stem cell types in the presentation by Dr. Carol Schuurmans at last year’s Vision Quest) and there has been an explosion of research into their capabilities. While challenges remain in controlling the development of induced pluripotent cells, this approach is desirable because the source cells can be cheaply and easily collected from the patient for stem cell transplantation.
Transplanting cells from one’s own body is advantageous for several reasons: first, because it avoids the rejection of cells from another person (which would be recognized as “foreign” by the body’s immune system) as well as any risk of transmitting undetected diseases from the donor; and second, because it makes it unnecessary to obtain true stem cells from human fetal tissues. However, for the treatment of genetic diseases, like retinitis pigmentosa, Stargardt disease, Usher syndrome, etc there is one big disadvantage: stem cells derived from the very person who is being treated, will normally have the same gene mutations that led to vision loss.
Recently, scientists from the University of Wisconsin-Madison showed that they could correct a genetic mutation in induced pluripotent stem cells, and subsequently grow generations of disease-free ipSCs derived from them. This process did not increase the risk of potential cancer-causing mutations in the treated ipSCs.
“This study showed that the process of gene correction is compatible with therapeutic use,” says Dr. Sara Howden, the postdoctoral research associate who wrote the research paper describing this study. The study is being published in a very prestigious and reliable scientific research journal, the Proceedings of the National Academy of Sciences (USA).
This team’s approach was original and ingenious. Instead of the gene therapies that are being tested in clinical trials today, which use modified viruses to carry new genes into the cells, these scientists used a technique called homologous recombination. They started with skin cells from a patient with gyrate atrophy, a disease that causes progressive loss of visual acuity and night vision, and manipulated these cells to create induced pluripotent stem cells. Of course, the new stem cells still carried the genetic mutations that cause gyrate atrophy; but then, through a careful series of treatments in the laboratory, the research team was able to correct the gyrate atrophy mutation, allowing them to grow and maintain a population of disease-free stem cells derived from the treated cells.
Dr. David Gamm, another scientist involved with the study, says that the ability to correct gene mutations in a patient's own induced pluripotent stem cells should increase the appeal of stem cell technology to researchers and clinicians working on genetic retinal diseases.
“Although further development certainly is needed before such techniques may reach the clinical trial stage, our findings offer reason for continued hope,” Dr. Gamm says. “Dr. Howden and our collaborative group have overcome an important hurdle which, when considered in the context of other recent developments, may lead to personalized stem cell therapies that benefit people with genetic visual disorders.”
Dr. Bill Stell, Director of Research Programs at The Foundation Fighting Blindness, agrees that this is a significant step forward. “However”, he notes, “even though this new method may give us more and better stem cells to use in therapies for retinal degeneration, we are still not very good at turning these unspecialized stem cells into rods and cones, nor at persuading these new rods and cones to connect with remaining retinal cells so that they can restore good vision. Donations to the FFB support many studies aimed at solving these problems, bringing us another step closer to a cure.