Prevention of Chronic Heart Failure after Myocardial Infarction

Selective inhibition of Periostin variant (PN1) by monoclonal antibody

Core Benefit

Administration of PN1 Ab only in acute phase will reduce fibrosis, heart remodeling, and improve prognosis in chronic phase after 3 months.
PN1 inhibition may also improve the patients with worsening chronic heart failure.

Background and Technology

Although prevalence of cardiac intervention has improved survival rate of acute myocardial infarction (AMI), development of heart failure in chronic stage remains to be the formidable issue.

Periostin (PN), an extra cellular matrix protein has been reported to play a crucial role in the heart failure, the effect of PN has been controversial.

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). He has found that full-length PN (PN1) is the culprit of heart failure, which is upregulated at acute phase of AMI, causes fibrosis formation and damages heart performance, while PN4 is homeostatic and helps avoid cardiac rupture.

Antibodies (Abs) that target exon 17 (PN1 Abs) have proved to attenuate fibrosis formation and heart enlargement, and remain cardiac performance.

Facts and Data

4 times of weekly 0.2mg/head i.v. administration of PN1 Abs reduced infarct size and heart weight at 8 weeks after AMI on rat AMI model.
Confirmed improvement of cardiac performance indicators at 8 weeks: LVEDP, LVDd, LVDs, FS, EF, +dP/dt, -dP/dt, plasma BNP level, etc.
Humanized monoclonal anti-human PN1 Ab established; (Kd < 10*E-10).

Published in Hypertension. 2016;67:356-361
# Preparing for journal which describes details and mechanisms.

Potential indications

AMI, Severe asthma, Atopic dermatitis, Intestinal bowel diseases, diabetic retinopathy.

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.

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-00099c