When I first started working for California’s stem cell institute in 2008 I would never have guessed that we would be funding 15 clinical trials by the end of 2015. Medical science usually does not move that fast. But I, like most people back then, probably thought about stem cell science too narrowly, mostly as leading to replacement parts.
Our current portfolio showcases five distinct ways that stem cell science can lead to potential therapies. And I suspect this list of “methods of action” as scientist like to call them, will grow.
We do have three classic replacement tissue projects. One seeks to mend injured spinal cords. One gives diabetics new insulin-producing cells and one replaces the layer of cells in the back of the eye that has been lost in a blinding disease called age-related macular degeneration. But even two of these trials are not simple cell replacement. Researchers grow the insulin-producing cells inside a porous pouch to protect them from the immune system and the eye cells are grown in a single layer on a synthetic scaffold.
Two of our trials use stem cells to release various cell signals that encourage repair. For the genetic form of blindness called retinitis pigmentosa (RP) the research team injects a type of adult nerve stem cell into the eye. There the injected cells release factors that protect the light receptors in the retina from damage and may trigger renewal of already damaged receptors. For patients who have experienced a heart attack, another team injects stem cells derived from donor heart tissue in hopes they will release cellular factors that increase new blood vessel growth and reduce scarring of heart tissue, which can reduce its ability to function
Since this is the year that Science magazine named the CRISPR gene editing technology, the discovery of the year, it seems appropriate that the largest segment of our clinical trial portfolio involves gene editing. However, all our trials use older techniques with some track record of clinical safety—unlike CRISPR. Three different teams are using three different gene modification techniques to make HIV patient’s blood forming stem cells immune to the virus. Another team hopes to give sickle cell anemia patients a healthy form of the hemoglobin gene, which when mutated, causes the disease. That same research group is correcting a genetic error in a form of immune deficiency.
Attack Cancer Stem Cells
Then there comes the Mr. Hyde of the stem cell world, the cancer stem cell, which is generally attributed to be the cause of relapse after cancer therapy. Three of our teams use different agents to directly attack cancer stem cells in the hope of stopping the deadly cycle of treatment and relapse so many cancer patients face. Two teams are treating various solid tumors including colon, lung and breast cancer. The third trial is treating the blood cancer leukemia. The latter uses a drug with my favorites name cirmtuzumab, an antibody named for CIRM.
Our last two trials also target the Mr. Hyde of stem cells, but in these two trials the teams hope to empower a patient’s own immune system to knock out the treacherous cancer stem cells. They both use a type of immune cell called a dendritic cell, which is first exposed to proteins from the cancer stem cells of the patient, then grown in the lab and injected into the patient. Dendritic cells serve as a kind of Pinterest sign board displaying the identity of the cancer stem cells to the patient’s immune system. This disclosure of Mr. Hyde invites the patient’s immune cells to attack the cancer stem cell. One team treats the skin cancer melanoma and the other treats the brain cancer glioblastoma.
These clinical trials range from early phase safety studies to late stage trials aimed at providing final proof of effectiveness prior to approval for broad use by the Food and Drug Administration. While it is unlikely all 15 potential therapies will make it through all phases of testing and get to the market for patients, historical odds suggest several will, completing an amazingly fast emergence of a new field of medicine.