While medicine is advancing rapidly, there are still many rare and intractable diseases for which no treatment has been found. The scientific community believes that regenerative medicine technology utilizing stem cells can cure these rare and intractable diseases. Stem cells are primitive cells that can grow into various cells that make up the body, such as bones, brain, muscles, skin, and heart.
The scientific community believes that if stem cells are administered into a patient's body, they can autonomously locate damaged areas and regenerate the damaged tissues. Compared to other treatments, the risk of side effects is also lower. If stem cell therapies are successful, they could offer new hope for diseases such as Parkinson's disease, epilepsy, and diabetes, which currently have no fundamental treatment methods.
The international journal Nature reported on the 20th that there are currently 116 clinical trials for regenerative medicine using stem cells being conducted worldwide, noting that this could be a turning point for the field, which is embroiled in ethical and political controversies. So far, a total of 12 stem cell therapies have been commercialized after receiving approval from health authorities around the world, four of which were developed in South Korea. Although South Korea has stagnated over the last 10 years, there is a possibility it may regain its status as a powerhouse in stem cell therapies.
◇Parkinson's disease and epilepsy: repairing damaged cells with stem cells
Stem cells are broadly divided into embryonic stem (ES) cells, induced pluripotent stem (iPS) cells, and adult stem cells. Embryonic stem cells are created from embryos (fertilized eggs) that are 5 to 6 days old, which later grow into all types of human cells. iPS cells are created by introducing specific genes or proteins into mature cells to revert them to an early embryonic stem cell state. Adult stem cells refer to primitive cells present in adults. When cells in various organs or tissues of the body are damaged, they grow to replace those damaged cells.
Scientists refer to adult stem cells as first-generation stem cells, while embryonic stem cells and iPS cells are called second-generation. About half of the ongoing stem cell clinical trials utilize embryonic stem cells, while the rest use induced pluripotent stem (iPS) cells and adult stem cells. Among these, the most prominent research is the clinical trial for Parkinson's disease.
Parkinson's disease is a degenerative brain disorder resulting from the reduction of dopamine nerve cells responsible for involuntary muscle movements, leading to tremors in the limbs and a shuffling gait. The scientific community believes that by differentiating stem cells into dopamine cells and transplanting them into the brain, Parkinson's disease can be fundamentally cured. Currently, there are 12 ongoing clinical trials for Parkinson's disease using stem cells.
Bluerock Therapeutics, a subsidiary of German pharmaceutical company Bayer, conducted a clinical trial in 2022, transplanting dopamine cells derived from embryonic stem cells into 12 Parkinson's disease patients. After injecting the stem cell therapy into the patients' brains, positron emission tomography (PET) confirmed that the transplanted cells were generating dopamine, a neurotransmitter. No significant adverse reactions were noted in the patients. Based on these Phase 1 clinical trial results, Bluerock is currently conducting Phase 2 trials.
Clinical trials for epilepsy are also in progress. Epilepsy is a condition that causes muscle spasms due to the excessive electrical signals from damaged brain cells. Neurona Therapeutics from the United States conducted a clinical trial with 10 patients with epilepsy whose symptoms were not controlled by existing medications. They created interneurons from embryonic stem cells to connect between nerve cells and transplanted them into the patients' brains.
The trial results showed that the frequency of seizures for patients who had been unable to live normally due to frequent seizures dropped to zero one year after transplantation, and this effect was maintained for two years. No serious side effects were reported, leading the U.S. Food and Drug Administration (FDA) to undergo expedited approval procedures last June.
◇Eye diseases and diabetes treated with reprogrammed stem cells
Retinal diseases caused by damage to the optic nerve can also be treated with stem cells. Currently, there are 29 ongoing clinical trials for stem cell treatments for eye diseases, including age-related macular degeneration.
Age-related macular degeneration is a condition where the macula, which receives light in the retina (the nerve cell layer inside the eye), loses its function due to aging and inflammation, and in severe cases, it can lead to blindness. iPS cells, rather than embryonic stem cells, are mainly used for the treatment of age-related macular degeneration. This offers a way to obtain treatments anytime and anywhere through reprogramming, which reverses the developmental clock of mature cells.
The cornea at the front of the eye is also treated with iPS cells. Researchers from Osaka University in Japan announced last month that they successfully improved vision loss due to corneal damage for the first time using iPS cells made from the cells of healthy donors. Of four patients who had experienced severe vision loss, three reported improvements in vision following stem cell transplantation, and these effects persisted for over a year.
Previously, corneal cells made from stem cells extracted from patients' healthy eyes were transplanted; however, there was a possibility of damaging the eye during the extraction process. If both eyes were damaged, it would be impossible to perform the procedure. In this instance, blood cells received from healthy donors were turned into primitive iPS cells that were then differentiated into corneal cells and transplanted to areas where scars had been removed. This opens up possibilities for treating more patients.
Recently, a stem cell treatment for diabetes was also developed. A joint research team from Peking University and Nankai University proved the treatment effect for type 1 diabetes by transplanting stem cells into a 25-year-old patient for one year without issues last September. Type 1 diabetes is a condition where immune cells destroy pancreatic cells, preventing them from properly secreting insulin, which is the hormone that regulates blood sugar levels.
The research team transformed the cells extracted from the patient's pancreas into iPS cells using chemical substances, then transplanted them into the patient's abdomen. The pancreas contains clusters of cells that secrete insulin, resembling an island-like formation. The clinical trial results indicated that the patient began producing insulin on day 75 post-transplantation and reported no significant side effects for the following year.
◇South Korea saw stagnation for 10 years but is now reactivating
In South Korea, the development of stem cell therapies is also active. Among the 12 stem cell therapies that have been commercialized worldwide, four are domestic products. Starting with Pharmicell's heart attack treatment "Hearticellgram" in 2011, followed by Medipost's degenerative knee cartilage treatment "Catisstem," ANTEROGEN's chronic fistula treatment "Qupistem," and finally CorestemChemon's Lou Gehrig disease treatment "Neuronata-Al," all received domestic approval.
South Korea led stem cell research by conducting the second most clinical trials after the United States from the early 2000s to the mid-2010s. However, for the past 10 years, the following approved items have rarely emerged. Kangstem Biotech initially drew attention as the fifth approval contender while conducting Phase 3 clinical trials for an atopic dermatitis treatment, but it recently failed to demonstrate statistical significance in the primary evaluation criteria. Other companies, including Pharmicell and Nature Cell, have also applied for approval from the Ministry of Food and Drug Safety, but their requests were denied.
However, given the ongoing advancements from latecomers, it is too early to dismiss expectations. S.Biomedics is developing a Parkinson's disease treatment utilizing embryonic stem cells. Since May of last year, it has been conducting Phase 1 and 2a trials on 12 Parkinson's disease patients in South Korea, marking the first such clinical trials in Asia. Additionally, the company EN001-CMT is developing a next-generation mesenchymal stem cell therapy for Charcot-Marie-Tooth disease type 1A, a rare intractable disease that causes muscle atrophy in the hands and feet. Mesenchymal stem cells are obtained from tissues such as umbilical cords, bone marrow, and fat.
Reference materials
Nature (2024), DOI: https://doi.org/10.1038/d41586-024-04160-0
The Lancet (2024), DOI: https://doi.org/10.1016/S0140-6736(24)01764-1