Japan approves the world’s first treatment made from reprogrammed human cells

Acute 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 a risk of infection and cranial nerve damage, as well as decreased long-term quality of life.

ReHeart addresses these unmet medical needs. The transplant is performed by surgery on 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 of eight patients with severe heart failure, a trend toward improvement was confirmed in four patients, with maximal oxygen consumption (peak VO2) increasing by more than 10 percent at 52 weeks post-transplant.

Neurons are “implanted” directly into the brain

The second approved product is Amusepri (generic name: laguneprocell) from Sumitomo Pharma and Ractthera. 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 treatments, including preparations containing levodopa.

Parkinson’s disease is a neurodegenerative disorder that causes motor symptoms such as limb tremors and muscle stiffness due to the progressive loss of dopaminergic neurons in the brain. Current drug treatments are treatments to relieve symptoms, not a primary way to replace lost neurons.

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

In a trial conducted by doctors at Kyoto University Hospital, four of the six Parkinson’s patients analyzed showed improvement in their off-duty scores (the score when the drug’s effect wears off) on the Motor Diagnostic and Therapeutic Symptom Rating Scale (MDS-UPDRS Part III) 24 months after the transplant. The researchers confirmed that the cells remained viable in all six patients at the transplant site.

The world’s first manufacturing facility and industry-academia collaboration

Located in Suita, Osaka Prefecture, SMaRT is responsible for the production of Amshepri and is the world’s first commercial manufacturing facility dedicated to regenerative medicine and cell-based medicines derived from donor iPS cells. The iPS cells used as raw materials for the product come from stock provided by the iPS Cell Research Foundation of Kyoto University, and the differentiation induction and manufacturing techniques 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 can also be said that the fact that this pioneering approval came from Japan was structurally inevitable. This is because the entire supply chain has been almost entirely completed in Japan, from the creation of the core technology by Shinya Yamanaka, winner of the 2012 Nobel Prize in Physiology or Medicine, to the supply of iPS cells by the iPS Cell Research Foundation of Kyoto University, the differentiation induction and manufacturing technologies developed by Kyoto University and other institutions, the establishment of the SMaRT commercial manufacturing facility, to the development of university startups and the entry of major pharmaceutical companies.