AMED adjusts its R&D funding for the medical field — 12 billion yen allocated to 114 issues

The Expert Committee on Promotion of Healthcare Policy held a meeting on June 14, and AMED President Yoshinao Mishima outlined the second round of adjustments for funds related to research and development (R&D) in the medical field for this fiscal year. A total of 12.1 billion yen will be allocated to 114 projects in accordance with the President's five policies. The final decision will be made official at a subsequent meeting of the Headquarters for the Promotion of Healthcare Policy. Mishima commented, "This is the final year of our second medium- to long-term plan, and we have added the area of 'acceleration and increase of research and development for practical application including out-licensing to companies,' to make a more desirable allocation plan based on discussions toward the third plan. We selected projects that have been steadily implementing R&D and advancing research and could trigger new advances in R&D and the creation of new values by providing a boost through adjustment funds."

17 projects were selected in the newly established category. In one of these an anticancer drug based on the induction of ferroptosis (cell death associated with iron-dependent lipid oxidation) in cells undergoing malignant transformation and proliferation will be developed. This anticancer drug is expected to be effective against any type of cancer and has been tested successfully in investigator-initiated phase I clinical trials on multiple types of cancer. The adjustment funds will allow for the early initiation of phase II trials by identifying biomarkers to stratify patients according to the likelihood of strong drug response. Since attempts to expand the culture of the diarrhea-causing viruses have not been successful, the molecular mechanism has not been fully understood, and the production of viruses in sufficient quantities for drug discovery has remained a bottleneck. However, a new cell technology for large-scale virus propagation has also been created. The adjustment funds will support clarification of the usefulness and robustness of this technology and construction of a supply structure to facilitate out-licensing of the technology to companies. Acceleration of drug discovery, such as the development of antiviral drugs and diagnostics for diarrhea-causing viruses, is expected.

Five projects were selected to strengthen cooperation among businesses, projects, and fields by using fundamental technologies and centers. For example, the function of an immune cell population known as "THA cells," a new subset of helper T cells that have both antibody production-inducing ability as well as cytotoxic activity and proliferate particularly in inflammatory organs in autoimmune diseases, is being analyzed to clarify pathological mechanisms. The adjustment funds will allow for a detailed analysis of THA cells in terms of gene expression alterations, interactions with other cells in the microenvironment, and disposition associated with pathology. Moreover, drug discovery targets for the regulation of organ damage onset in autoimmune diseases will be explored, and therapeutic target molecules will be identified. This is expected to lead to the development of novel drug discovery and autoimmune disease therapies that directly and selectively approach the autoimmune responses of THA cells.

Three projects were selected to foster young researchers who will lead the development of the medical field and the entry of human resources from different fields. One example is an autologous tissue artificial valve for children that can be prepared simply by implanting a template under the skin is being prepared, and as a result of long-term implantation experiments in large animals, the valve was found to have regenerative abilities and excellent antithrombogenic properties. The adjustment funds will allow for an increase in the number of implantation experiments in large animals, evaluation of valve function over time and from multiple angles, and acquisition of the knowledge necessary for clinical application, including the safety and effectiveness of the implanted prosthetic valve, and ultimately, its early practical application. The prosthetic valve is expected to grow (change in size) as the pediatric patient grows, providing various benefits, such as a decreased number of reoperations required during years of growth.

Eleven projects were selected to strength international cooperation and improve domestic systems and infrastructures that contribute to its promotion. In this area, a mutation signature analysis of kidney cancer samples from 11 countries in an international collaborative study revealed region-specific mutation signatures and found a mutation signature (SBS12) of unknown cause characteristic in Japanese patients (found in about 70% of Japanese patients, compared to 2% or lower in other regions including Thailand). Therefore, with the adjustment funds, a large-scale mutation signature analysis in kidney cancer patients across Japan will be conducted to identify the causes based on the regional distribution of patients with SBS12, as well as epidemiological and clinical information. This will contribute to the prevention and development of new treatment methods for kidney cancer in Japanese people and will lead to international collaborative research with neighboring East Asian countries based on the findings obtained. Another project involved developing a new method for concentrating schistosome DNA in aqueous environments within a short time without the need for an electric power source. This technique allows the collection of a large number of samples in a quick and convenient manner. The adjustment funds will allow testing of the technique in various water environments in Kenya to further demonstrate its effectiveness. This will contribute to the early commercialization and international standardization (ISO certification) of this technique as a new technology originating from Japan.

Seventy-eight projects were selected for further acceleration and enhancement of cutting-edge research and development and environmental improvement for the realization of advanced medical care. An example here is a treatment method for fetuses with fetal renal failure in which a xenogeneic fetal kidney is transplanted subcutaneously into the fetus in utero to sustain life. The method was confirmed to be effective in rats ahead of schedule, and the project is now ready to proceed with studies on large animals. Using the adjustment funds, genetically modified porcine fetal tissue in humans will be transplanted into fetal crab-eating macaques to suppress immune rejection. Advanced research using technologies to reduce risks of immune rejection and infection will be integrated to enhance research and development on fetal xenotransplantation. This will allow low-fetal-risk xenotransplantation technology originating from Japan to achieve the nonclinical PoC stage ahead of U.S. technologies, which have been ahead, and gained international superiority. Research and development is being conducted to establish safety evaluation methods and guidelines for xenotransplantation, and the adjustment funds will be used to standardize preoperative and postoperative management methods, including immunosuppressive therapy, and to conduct multilateral immune response analysis using various techniques, such as spatial gene expression analysis, in an organ transplantation model from genetically modified pigs to crab-eating macaques. Long-term safety evaluation methods will be established, and guidelines reflecting scientific evidence will be developed.