• Dr. Katsunori Nonogaki has developed the novel ultrasound irradiation device, which can improve the autonomic nervous system activity and peripheral circulation. In addition, the ultrasoud device can improve hypertension and hyperglycemia within 20 min in subjects with drug-resistant hypertension and diabetes. Our initial device was approved in Japan (226AIBZX00028000). This device will be avaliable for the treatment of 1) muscle pain, 2) the autonomic neural dysfunction and stress-related disorders, 3) hypertention, and 4) diabetes. Moreover, the device will be usefull for your healthy life and aging care.

Our aims are to export the device internationally. We seek the investment and international business partners.

• Diabetes induces several complications, including retinopathy and nephropathy. In patients with type 1 diabetes as well as those with type 2 diabetes, pancreatic beta cells have reportedly decreased. Therefore, regeneration therapy of pancreatic beta cells may be very effective for major populations of diabetic patients. We discovered a neuronal network, from the liver, which selectively elicits pancreatic beta cell proliferation (Science 2008, Fig.). In a murine model with insulin-deficient diabetes, stimulation of this network improved diabetes. Thus, building devices which regulate the inter-organ neuronal network may lead to “regenerative therapy” for diabetes which regenerates pancreatic beta cells in the pancreas using patients’ own cells and patients’ own systems. We hope to conduct collaborative research with a willing company for a practical application of this technology.

• McH/lpr-RA1 mice are recombinant congenic mice descended from MRL/lpr and C3H/lpr mice and develop arthritis, vasculitis, and sialadenitis with high frequency and severity, with severe pannus formation similar to rheumatoid arthritis, polyarteritis nodosa, and Sjogren's syndrome. On the other hand, McH/lpr-RA1 mice do not develop systemic lymphadenopathy and severe nephritis as seen in MRL/lpr mice, so they are easy to breed and maintain and can be used for long-term drug administration experiments.

Development of diagnostic and therapeutic agents for collagen diseases. It can be applied to the elucidation of the mechanism of onset of immunological adverse events caused by immune checkpoint inhibitors and the development of drugs to prevent the onset of such events, etc. Industry-academia collaboration with pharmaceutical companies, test reagent companies, etc. is possible.

• Bone marrow stromal cells have great advantages since they are already applied to patients either by auto- or allo-transplantations, can be harvested in large numbers (10 million cells within several weeks) as adherent cells from bone marrow aspirates, and are with low risk of tumorigenesis. We have established a system to induce neural precursor cells from human bone marrow stromal cells by introducing cells with Notch intracellular domain gene plasmid followed by culturing in neurosphere method. This induction system successfully generates neural precursors which were effective for stroke (J. Neuropathol. Exp. Neurol. , 2005; J Cereb Blood Flow Metab, 2009). They could be further developed into dopamine producing neurons by treating them with cytokines including GDNF (J. Clin. Invest, 2004). The efficiency and safety of induced dopamine neurons were confirmed by rat and monkey model of Parkinson's disease. Importantly, long-term survival of auto-transplanted induced dopamine neurons were verified by 11C-CFT PET scan (J. Clin. Invest, 2013).

We hope to collaborate with companies and research groups who are willing to utilize our system.

Autism spectrum markers:
Measuring histone modifications in sperm may be able to predict the risk of neurodevelopmental disorders in the next generation.

It is known that the highest risks with regard to the development of developmental disorders in children are ageing and premature birth in both parents, and it has been repeatedly epidemiologically reported that the risk is higher in ageing fathers than in ageing mothers among the parents. Conventionally, sperm are only examined under a microscope to check sperm count, morphology and motility, but not at the molecular level. The present invention is an innovative method that focuses on epigenetic molecular markers.

• While birthrates are falling rapidly, developmental disorders are on the rise
• Focus on plastic epigenetic molecules as a successional effect of paternal ageing.
• Sperm testing can be performed non-invasively.
• Suitable as a quality check for sperm donors etc.

The combination of sperm histone modifications and relevant epigenetic factors (DNA methylation, microRNAs) in combination with the sperm panel test will enable highly accurate sperm quality testing.

Autism spectrum markers:
Measuring histone modifications in sperm may be able to predict the risk of neurodevelopmental disorders in the next generation.

It is known that the highest risks with regard to the development of developmental disorders in children are ageing and premature birth in both parents, and it has been repeatedly epidemiologically reported that the risk is higher in ageing fathers than in ageing mothers among the parents. Conventionally, sperm are only examined under a microscope to check sperm count, morphology and motility, but not at the molecular level. The present invention is an innovative method that focuses on epigenetic molecular markers.

• While birthrates are falling rapidly, developmental disorders are on the rise
• Focus on plastic epigenetic molecules as a successional effect of paternal ageing.
• Sperm testing can be performed non-invasively.
• Suitable as a quality check for sperm donors etc.

The combination of sperm histone modifications and relevant epigenetic factors (DNA methylation, microRNAs) in combination with the sperm panel test will enable highly accurate sperm quality testing.