Japan Approves the World’s First Treatment Made With Reprogrammed Human Cells

Severe heart failure is a serious condition that worsens over time, and the only treatment options are a heart transplant or a heart-assisted artificial heart. However, heart transplantation is hampered by a shortage of donors and age restrictions, and artificial hearts also carry the risk of infection and cranial nerve damage, as well as long-term decline in quality of life.

ReHeart addresses these unmet medical needs. The transplant is performed via a surgery in the left side of the chest, with three sheets of cardiomyocytes attached to the surface of the heart. Signaling proteins secreted by the transplanted cells help increase blood flow and repair tissue. In a national multicenter collaborative study that included eight patients with severe heart failure, a trend toward improvement was confirmed in four patients, with peak oxygen consumption (VO2 peak) increasing by more than 10 percent at 52 weeks post-transplant.

Neurons “Implanted” Directly Into the Brain

The second approved product is Amusepri (generic name: laguneprocell) from Sumitomo Pharma and Racthera. It consists of precursor cells destined to become dopamine-producing neurons made from donor iPS cells. It is indicated for improving motor symptoms in patients with Parkinson’s disease who have had an inadequate response to existing drug therapies, including levodopa-containing preparations.

Parkinson’s disease is a neurodegenerative disorder that causes motor symptoms such as tremors in the limbs and muscle rigidity due to the gradual loss of dopaminergic nerve cells in the brain. Current drug therapies are treatments to alleviate symptoms, not a fundamental approach to replacing lost nerve cells.

AmShepli aims to offer a new treatment option by transplanting progenitor cells from lost dopamine-making neurons directly into the brain. This transplant is performed using a minimally invasive type of brain surgery. Small holes are drilled in the skull, one on each side, and the cells are dispersed and injected into the capsule on both sides via three delivery routes.

In a physician-led trial conducted at Kyoto University Hospital, four of the six Parkinson’s disease patients analyzed showed an improvement in their off-time score (the score when the drug’s effect has worn off) on the Motor Symptoms Diagnostic and Treatment Rating Scale (MDS-UPDRS Part III) 24 months after transplantation. Researchers confirmed that the cells remained viable in all six patients at the transplant site.

World’s First Manufacturing Facility and Industry-Academia Collaboration

SMaRT, located in Suita City, Osaka Prefecture, is responsible for the production of Amshepri and is the world’s first commercial manufacturing facility dedicated to regenerative medicine and cell-based drugs derived from donor iPS cells. The iPS cells used as raw material for the product come from a stock provided by the Kyoto University iPS Cell Research Foundation, and the differentiation induction and manufacturing technologies are based on proprietary technologies from Kyoto University and other institutions. For example, Eisai’s cell purification technology is used in part of the manufacturing process; the product was made possible through collaboration between industry and academia, with contributions from various institutions.

It could also be argued that the fact that this groundbreaking approval came from Japan was structurally inevitable. This is because the entire supply chain has been almost entirely completed in Japan, from the establishment of the basic technology by Shinya Yamanaka, winner of the 2012 Nobel Prize in Physiology or Medicine, to the supply of iPS cells by the Kyoto University iPS Cell Research Foundation, the differentiation induction and manufacturing technologies developed by Kyoto University and other institutions, the establishment of the commercial manufacturing facility SMaRT, and even the development of university startups and the entry of major pharmaceutical companies.