Daniel’s son Harry, a cheerful little boy shown wearing big blue spectacles and an even bigger smile, was born with a rare genetic disorder called Usher’s Syndrome. This disorder is characterised by the loss of hearing from birth, and the progressive degeneration of his retina which will lead to blindness at adolescence. While cochlear implants have given Harry the ability to hear, there is currently no cure for the impending loss of his eyesight.
Doing what any loving parent would do, Daniel and his wife sought treatment for their son, now 7 years old. The couple reached out to researchers at the Centre for Eye Research Australia (CERA), who were working on developing a cutting-edge stem cell treatment for inherited eye diseases, using induced-pluripotent stem cells (iPSCs) derived from the patient.
For the uninitiated, iPSCs are the latest technological advancement in the stem cell field.
Traditional sources of human stem cells are largely limited by accessibility. Embryonic stem cells can only be found in embryonic tissue, while adult somatic stem cells may be found in tissues and organs but at extremely low frequencies. This is circumvented by the technology for developing iPSCs.
iPSCs require specialized adult cells, such as skin cells or fibroblasts from the patient. These cells are then “re-programmed” to a pluripotent state resembling embryonic stem cells and subsequently differentiated into a different specialized cell type of choice, under specific cell culture conditions.
While advancements in various areas of the stem cell field were enthusiastically showcased at the 2018 ISSCR conference, iPSCs undoubtedly took the spotlight among many of the talks presented.
With the recent advent of the CRISPR-Cas9 technology for precision DNA editing, scientists are now able to directly add or remove gene sequences from the iPSCs reliably. For young Harry, this would mean that there is a potential cure on the horizon for his eventual blindness—something which was just a pipe dream a decade ago.
Indeed, researchers at CERA are utilizing this new combinational strategy. In their upcoming clinical trial, skin cells from patients like Harry will be re-programmed into iPSCs, the aberrant gene sequence corrected using CRISPR-Cas9 editing, and the iPSCs subsequently differentiated into retinal photoreceptor cells for transplantation back into the patient.
Other iPSC-driven therapies were also presented at the meeting, ranging from growing new neurons that are genetically corrected for neurological diseases to growing new skin grafts from white blood cell-derived iPSCs.
Momentum in the cell therapy field has been accelerating in recent years, with credit to the chimeric antigen receptor T cell (CAR-T) technology, which has been achieving significant positive outcomes in recent clinical trials for targeted cancer immunotherapy. Comparatively, stem cell therapies in general have yet to receive the equivalent amount of attention, despite the incredible potential in regenerative medicine. Why is this so?
A key reason for this is that both forms of cell therapies are fundamentally different in nature, thus the accompanying expectations. CAR-T therapies are designed simply to eliminate the specific cancer cells, while ensuring that it does not cause life-threatening immunological reactions in the patient. Regenerative stem cell therapies, on the other hand, are expected to repair and restore lost functions in damaged organs and tissue structures that are often highly complex, while ensuring that the implanted stem cells remain under control and do not generate tumors themselves. Expectations for “miracle” stem cell therapies are thus relatively high.
In order to develop iPSC-driven therapies that fulfill the safety and efficacy standards for clinical trials, basic academic research is required to continue building our knowledge on the biology of iPSCs. If current CAR-T immunotherapy trends are of any indication, it is highly likely that as the iPSC field matures, demand for the clinical translation of various regenerative iPSC therapies will also increase substantially.
Even though most iPSC clinical trials are still currently at early phase or the pre-clinical stage, pharmaceutical companies are already beginning to explore their options for incorporating process development and industrial manufacturing. Automation of labor-intensive processes will result in lower production costs and increased output of consistently high-quality stem cell therapy products, both of which are qualities that would not only appeal to pharmaceutical companies, but also directly benefit the patients themselves.
What better motivation?
At the end of Daniel Feller’s heartfelt speech (which you can watch on YouTube here), he thanked the stem cell community for giving him hope in curing his son’s genetic disease. He also beckoned his son Harry onto the stage.
The small boy came to his side, and although he was initially overwhelmed with shyness, Harry eventually found his courage and spoke to the microphone, blushing profusely as he addressed the crowd—academic, clinical, and industrial alike.
“Hello, my name is Harry. Thank you all for being here and thank you all for being so clever.”