• 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.

• Strong points
• Anemia is a very prevalent disease. Nevertheless, an effective therapy is yet to be discovered. Erythropoietin is effective only for those with renal dysfunction. We have found that inhibition of an enzyme for epigenetic regulation results in a prominent increase of erythropoiesis, pointing to a new target for anemia therapy. We have also generated a new, cell-based assay system for the enzymatic activity and carried out small molecule screening.
• Collaboration with industry partners
• We are seeking a collaboration to accelerate the development of new anemia drugs based on these findings. Together we will advance the development of the candidate molecules currently identified as well as conduct further screening of larger chemical space for better candidates and/or for drug repositioning.

• Effective drug delivery to central nervous system is promising as a new therapeutic strategy against various central nervous system disorders. However, it represents a challenge because systemic delivery is always hindered by blood brain barrier, and local delivery cannot be effective because of the restricted distribution. Recently, local drug delivery system that can achieve robust distribution of the infusates by maintaining a pressure gradient at the tip of the infusion catheter during infusion has developed. Although this method is promising, there still exist several problems as loss of infusates by backflow through catheter tract or inconsistent distribution. We recently developed a method to deliver agents with this method under MRI guidance, and now performing clinical trial to treat recurrent gliomas.

Focal central nervous system disorders such as tumor, epilepsy, and parkinson's disease can be the target for application of this technique. Developments of the new catheters and pre-infusional similation systems are on their way. We are searching for effective collaborative research in this field.

• AIMS: This invention is to support the doctor’s prescription for diabetes and metabolic syndrome, especially in Japanese Clinic (Patent: JP 4176438).
• PROBLEM TO BE SOLVED: To perform a further efficient preparation by providing information for original medicine and generic medicine in the preparation.
• SOLUTION: The medicine price, pharmacologic effect and the like of each of original medicine and generic medicine are preliminarily recorded in a medicine database, and a generic medicine corresponding to the original medicine inputted by a doctor is automatically retrieved and displayed on a display. When the total number of the inputted medicine exceeds a number determined by insurance medical care, the generic medicine is retrieved so that the drug price of the group of the same usage is a prescribed amount or less. Welcome to your investment or co-operation.

• All the living organisms generate energy from molecular oxygen to maintain their own lives. Once the concentration of oxygen falls down, life activity gets severely hampered and it could sometimes cause death. Typical examples that are related to local hypoxia are ischemic heart disease, stroke and kidney disease.
• We focus on the function of prolyl hydroxylase (PHD) as a sensor to detect the hypoxia, and we are developing drugs to treat ischemic injury by controlling hypoxia.

Currently, we have several compounds that inhibit the PHD. We want to commercialize in conjunction with pharmaceutical companies in Japan and overseas, advancing our non-clinical studies for clinical development.

• We succeeded in generating highly developed cultured C2C12 myotubes by manipulating intracellular Ca2+ transients with electric pulse stimulation (EPS), that are endowed with similar properties to in vivo skeletal muscle in terms of (1) excitation-induced contractile activity as a result of de novo sarcomere formation, (2) higher energy expenditure (as assessed by AMPK activation), and (3) improved insulin responsiveness (as assessed by exofacial myc-GLUT4 translocation assay).

Taking advantage of our “in vitro Exercise Model", our innovation will be an excellent alternative for the animal experimentation that can be applicable for a wide array of skeletal muscle research including drug screen.

• 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.

• Complexity of the cardiac contraction sequence is still not fully understood because the dynamic mechanical excitation process, which directly correlates with contraction, cannot be accurately measured by CT, MRI, SPECT, or conventional ultrasound. By developing a noninvasive novel imaging modality with high temporal and spatial resolutions (US patent 5840028), we have detected the minute mechanical response (velocity component) to the propagation of the action potential in the human heart or to detect the propagation of the vibrations along the heart wall caused by the valve closure (Fig. 2).
• By applying the same procedure to the human arteries, the regional change in wall thickness caused during one cardiac cycle can be measured with high spatial resolution (Fig. 1). From the measurement, the regional elasticity of tissue surrounding atherosclerotic plaque can be determined. By comparing the pathological findings with the distribution of elasticity, elasticity of lipid and that of fibrous tissue were determined. Thus, each point inside the plaque is classified into lipid or fibrous tissue using transcutaneous ultrasound (Fig. 3).

This novel method offers potential as a diagnostic technique for detection of plaque vulnerability with high spatial resolution.
We are prepared to provide academic consultations to companies interested in our research.