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Aim for clinical applications by developing innovative therapies and practicing translational research based on findings obtained from pathological studies at the molecular level

1) Molecular therapy for cardiovascular disease

We are working towards elucidating the pathology of various cardiovascular diseases at the molecular level and are developing novel molecular therapies. Osaka University has identified the long-term effectiveness of HGF (hepatocyte growth factor) gene therapy for lower limb ischemic disease in Phase I/IIa clinical trials, while Phase III trials in the United States began in 2014. In Japan, we plan to implement advanced medical treatment at seven universities, and progress has already been made at the Department of Geriatrics and Hypertension at Osaka University. Moreover, it has been reported that periostin (PN) is associated with various inflammation-related diseases including heart failure [1,2], triple-negative breast cancer cell metastasis, diabetic retinopathy, asthma, aneurysm, arteriosclerosis, cerebral infarction and osteoarthritis [3], and we are independently developing a PN-specific neutralizing antibody (patented PCT approved) and pursuing basic research for its therapeutic application. Regarding nucleic acid therapeutics, we are conducting clinical trials for arteriovenous fistula in dialysis patients using NFkB (nuclear factor kB) decoy oligonucleotides.

Figure 1

2）Establishment of new therapies and early diagnosis methods for Alzheimer’s disease

We are studying the mechanism of tau pathology in Alzheimer’s disease [4, 5] and are working towards the development of therapies. We are also beginning clinical research aiming at the development of minimally invasive diagnostics that enables ultra-early diagnosis of dementia.

3）Elucidation of the pathology of ischemic cerebral vascular injuries and development of therapeutic treatments

Research on the development of novel therapies using RANKL (a NFκB activating receptor ligand) partial peptide [7], which targets the RANKL/RANK system [6] involved in inflammation control after cerebral infarction, and anti-thrombotic vaccine for the treatment of cerebral infarction.

Figure 2

4) Vaccine therapies targeting lifestyle disease

We believe that novel antibody-induced therapeutic vaccines are an option for the treatment of lifestyle diseases and are currently working towards the development of numerous vaccines beginning with hypertension vaccines targeting angiotensin II.

5) Skin ulcer treatments based on novel antimicrobial peptides

The novel antimicrobial peptide AG30 is a peptide that consists of both antibacterial and angiogenic properties. We aim to make use these properties and develop the SF peptide (a modified version of AG30) for the treatment of skin ulcers via external application. Clinical trials (Phase I/IIa) in patients with diabetic and lower leg ulcers are ongoing and will be followed by clinical trials for skin ulcer in patients with progeria (Werner syndrome).

【Publications】

1. Taniyama et al. Hypertension 67(2):356-61, 2016.
2. Zempo et al. Hypertension 39(11):764-768, 2016.
3. Chijimatsu et al. BMC Musculoskeletal Disorders. 16: 215, 2015.
4. Takeda et al. Nature Commun. 6:8490, 2015.
5. Takeda et al. Annals of Neurology 80:355–367, 2016.
6. Shimamura et al. PNAS 111(22):8191-6, 2014.
7. Kurinami et al. Sci Rep 6:38062, 2016.