• Using the yeast transcriptional activator Gal4 system, we reconstituted the production of amyloid beta (Aβ), responsible for Alzheimer disease. Aβ production could be monitored by the positive growth in the selection media or by the reporter enzyme (β-Gal). Utilizing familial Alzheimer disease mutants, we established a system to screen for mutations and chemicals that modulate gamma secretase activity and reduce toxic Aβ42.

Our yeast system can be used to screen for chemicals, natural products, food ingredients, genes, and mutations that modulate γ-secretase activity and block Aβ42 production specifically. We hope to conduct collaboration research with a willing company for a practical application of this technology in industry.

• Using the yeast transcriptional activator Gal4 system, we reconstituted the production of amyloid beta (Aβ), responsible for Alzheimer disease. Aβ production could be monitored by the positive growth in the selection media or by the reporter enzyme (β-Gal). Utilizing familial Alzheimer disease mutants, we established a system to screen for mutations and chemicals that modulate gamma secretase activity and reduce toxic Aβ42.

Our yeast system can be used to screen for chemicals, natural products, food ingredients, genes, and mutations that modulate γ-secretase activity and block Aβ42 production specifically. We hope to conduct collaboration research with a willing company for a practical application of this technology in industry.

Amyotrophic lateral sclerosis (ALS) is a representative intractable neurodegenerative disease, and the development of effective therapies is desired. A novel phase I trial of intrathecal administration of recombinant HGF protein was conducted at Tohoku University Hospital. Based on the results, a phase II trial (investigator-initiated clinical trial) to confirm efficacy and safety for ALS was conducted and completed at the Tohoku and Osaka University Hospital from 2016 to 2022. Although there was no statistically significant difference in the primary endpoint, additional analyses are currently ongoing. Clinical development of the same formulation for acute spinal cord injury is also underway.

Simultaneous development of a novel intrathecal formulation of recombinant HGF protein, and a medical device (a subcutaneous port with an intrathecal catheter) that enable repeated intrathecal administration for efficient and selective delivery to the central nervous system.

• We developed a novel rat model of ALS model (Nagai M, et al. 2001)
• Intrathecal continuous administration of HGF protein was confirmed to have a slowing effect on progression in this model
• Phase I and II clinical trials have been completed, and the efficacy is currently being verified through additional analysis

We have been working with Kringle Pharma, Inc., Keio University (Prof. Hideyuki Okano and Prof. Masaya Nakamura), and Asahikawa Medical University (Prof. Hiroshi Funakoshi) to develop this drug. Phase I and II clinical trials for ALS have been completed. In addition, a phase III clinical trial for acute spinal cord injury is near completion. Additional collaboration with pharmaceutical companies is planned.

• 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.

• We perform in-vitro or computational researches for development of medical devices. We develop a model of artery or bone to evaluate medical devices. And we apply optimization way for development of medical devices. Our main target is, currently, stent, or catheter.

Our collaboration company can be; medical equipment, device, medical image, MEMS, standardization, medical training, or polymer.

The response rate of systemic chemotherapy for metastatic lymph nodes is low. This invention presents the optimal values for solvent properties, especially viscosity, in a method for directly administering drugs to lymph nodes (lymphatic drug delivery system). In 2024, a specified clinical study (jRCTs021230040) on lymph node metastasis was started at the Iwate Medical University Hospital Head and Neck Cancer Center.

In systemic chemotherapy for metastatic lymph nodes, the amount of drug delivered to the metastatic lymph nodes is small. This is due to the increase in internal pressure caused by tumor growth in the lymph nodes and the disappearance of microvessels caused by the formation of tumor mass. In this invention, we clarified the optimal viscosity range of the solvent for the lymphatic drug delivery system, which directly administers drugs to lymph nodes.

• The amount of anticancer drug required to treat one metastatic lymph node is 1/100 to 1/1000 of the systemic dose.
• The drug can be administered into the lymph node under ultrasound guidance.
• An international patent has been filed for the solvent of the administered drug.

1. Treatment and prophylactic therapy of affiliated lymph nodes in head and neck cancer, breast cancer, etc.
2. Pharmaceutical companies aiming to develop drugs by drug repositioning and generics
3. Medical device manufacturers aiming to develop a dosing system

• HIV infection is one of most serious concern in infectious diseases. We will perform anti-HIV assays for unmet medical needs in control of HIV infections with established novel assays. We have developed reverse transcriptase inhibitor that has novel mechanism of inhibition, translocation-inhibition (J Biol Chem, 2009). Dr Kodama participated in the primary screening and development of a new HIV integrase inhibitor, elvitegravir (J Virol 2009), and a unique reverse transcriptase inhibitor, islatravir, which phase III clinical trials by the Merck & Co., Inc. will complete, soon. We have a representative resistant HIV strain-library for anti-HIV screening and several target oriented high through-put screening systems.

We can establish high through-put screening for new targets, so please consult with us individually. We are open to joint development requiring BSL3/P3 experimental facilities and academic guidance including other microorganisms.

• Podoplanin (PDPN/Aggrus/T1α), a platelet aggregation-inducing mucin-like sialoglycoprotein, is highly expressed in many cancers and normal tissues. A neutralizing monoclonal antibody (mAb; NZ-1) can block the association between podoplanin and C-type lectin-like receptor-2 (CLEC-2) and inhibit podoplanin-induced cancer metastasis, but NZ-1 reacts with podoplanin-expressing normal cells such as lymphatic endothelial cells. Recently, we established a platform to produce cancer-specific mAbs (CasMabs). The newly established LpMab-2 mAb reacted with podoplanin-expressing cancer cells but not with normal cells, as shown by flow cytometry and immunohistochemistry; therefore, LpMab-2 is an anti-podoplanin CasMab that is expected to be useful for molecular targeting therapy against podoplanin-expressing cancers.

We can produce cancer-specific mAbs (CasMabs) against all membranous proteins. CasMabs are expected to be useful for molecular targeting therapy without side effects.

• The artificial control of gene expression by synthetic oligodeoxynucleotides (ODNs) has been the subject of considerable interest. In particular, ODNs conjugated with a cross-linking agent have been expected to enhance the inhibitory effect. Recently, microRNAs (miRNA) endogenously expressed small regulatory non-coding RNAs, are recognized as playing a critical role in regulating gene expression and the great concerns have been raised about efficient antisense oligonucleotides against miRNAs. We have already demonstrated that ODNs bearing a 2-amino-6-vinylpurine (2-AVP) derivative exhibited efficient interstrand cross-linking to cytosine selectively. The unique structural features of AVP are to possess both the hydrogen bond donor-acceptor sites as recognition sites and the vinyl group as a reactive moiety in a single molecule. Recently, we have developed of the novel cross-linking agents, which are designed based on the unique structure of AVP. These derivatives can react to thymine at the complementary site with highly selective and efficient under neutral conditions. We hope to conduct collaborative research with a willing company for a practical application of this technology in industry.

• Marfan’s syndrome (MF) is a severe, systemic disorder of connective tissue formation. A variety of MFS therapies have been developed, including surgical therapy for aortic root aneurysm and dissection (AAD) that are life-threatening, traditional medical therapies such as β-adrenergic receptor or angiotensin II receptor blockers for slow aortic growth and to decrease the risk of AAD. However these treatments did not prevent tissue destruction in the AAD of MF. To develop preventive strategy for AAD, it will be necessary to identify molecular mechanisms of microfibril formation and an appropriate fibrillin-1 microfibril associated molecule. Recently, ADAMTSL6β, which is a microfibril-associated extracellular matrix protein contributes the regeneration of microfibril by promoting fibrillin-microfibril assembly. We try to develop ADAMTSL6β as a preventive medicine for AAD of MF by regeneration of fibrillin-1 microfibril assembly.

• Obesity induced the metabolic syndrome, which causes cardiovascular diseases. Obesity has now become a major health concern not only in developed countries but developing countries. However, diet and exercise are still major therapies. We discovered endogenous systems maintaining homeostasis of energy metabolism and revealed several neuronal networks among organs to be responsible for the regulation systems.
• 1) Afferent neuronal signals from adipose tissue regulate appetite and prevent over-eating during obesity development (Cell Metab 2006)
• 2) Neuronal network from the liver enhances basal metabolic rates to prevent obesity development when energy store is increasing (Science 2006) 3) Neuronal network from the liver suppresses adaptive thermogenesis in brown adipose tissue (Cell Metab 2012).

On the basis of these original discoveries, we are aiming at developing new drugs and/or building devices which regulate the inter-organ neuronal networks and hope to conduct collaborative research with a willing company for a practical application to obesity therapy.