Core Benefit
- Different mechanism from VEGF inhibitor or prevailing drugs.
- Minimize risk of side-effect by maintaining shortest-length Periostin variant
- Potentially useful for diabetic nephropathy, severe asthma, atopic dermatitis, Crohn’s disease, age-related macular degeneration, malignant tumors.
Background and Technology
Dozens of reports have suggested that Periotin (PN), an extra cellular matrix protein plays a crucial role in some diseases like cancer, angiogenesis, inflammation, atopic dermatitis and asthma. Recently, involvement of PN in proliferative diabetic retinopathy (PDR), and diabetic nephropathy (DN) have been reported from distinct groups.
Although PN has been considered as a promising therapeutic target, few inhibition effects had been reported other than knock-out animal or siRNA studies. More importantly, several researchers suggested that PN is homeostatically important and inhibition may cause side-effects.
The inventor has focused on effects of each of four PN variants; PN1 (full length), PN2 (without exon17), PN3 (without exon 21), PN4 (without exon 17, 21) and found that only PN4 is expressed in normal tissues. He has created neutralizing antibodies (Abs) that target exon 17 (PNEx17 Abs), and exon 21 (PNEx21 Abs) respectively. PNEx17 Abs have proved to attenuate fibrosis formation, while PNEx21 Ab reduced angiogenesis. Therapeutic effects have been confirmed for cancers, heart failure, and this time Abs were applied for PDR.
Facts and Data
Published in Experimental Eye Research Volume 153, December 2016, Pages 133–140
- PN Abs attenuated pathological, but not physiological angiogenesis in mice OIR (Oxygen-Induced Retinopathy) model.
- Humanized anti-human PN mAbs established; cross-reactive to mouse (Kd < 10*E-10).
- In clinical human samples, increase of VEGF did not directly correlated with PN expression.
Patent (Solely owned by Osaka University)
PCT/JP2006/326280 (JP, US, GB, FR, DE, AU, KR) All registered.
PCT/JP2008/061768 (JP, US, EP, CA, KR) JP registered.
PCT/JP2014/055861 (JP, US, EP)
Researcher
Associate prof. Yoshiaki Taniyama, Graduate School of Medicine, Osaka University, Japan
(http://www.cgt.med.osaka-u.ac.jp/cont/e_gr01_a.html)
Expectations
Start-up company Periotherapia is looking for investment partners in series C round for preparation of clinical trial, as well as co-development companies.Full experimental data and development status can be disclosed under CDA.
Project No. KJ-00099b