Drugs ～Others～
Establishment of a new strategy for the treatment of functional restoration in skeletal
muscle injury by tissue engineering using osteopontinederived SVVYGLR peptide
Principal
Investigator

Department of Oral and Maxillofacial Surgery,
Graduate School of Dentistry, Osaka University
Professor Susumu TANAKA

Project Outline
Skeletal muscle dysfunc�on with serious damages caused by injury or surgery, and congenital diseases with deformed or
poorly developed muscular �ssue such as cle� palate, conven�onal treatments including plas�c surgery occasionally failto obtain an adequate func�onal recovery. SVVYGLR (SV), -7amino-acid sequence derived from osteopon�n (SV pep�de) has
previously demonstrated strong angiogenic ac�vity, enhancement of the synthesis of collagen type III in myocardialﬁbrosis and capability for improvement of cardiac func�on through the diﬀeren�a�on of ﬁbroblasts to myoﬁbroblasts. Th ispep�de was also revealed to be easily degraded by pep�dase and show less adverse eﬀects, indica�ng highbiocompa�bility. Like myocardium, skeletal muscle is striated, but it is voluntary, composed of mul� -nucleated muscle
ﬁbers regenerated by �ssue -speciﬁc muscle stem cells called satellite cells which proliferate and diﬀeren�ate to form
mature myoblasts.
Development roadmap

Given the potent role of SV pep�de on the repair of injured
skeletal muscles like myocardium, it might also
contribute to func�onal restora�on a�er the injury. Our
preliminary study using rat volumetric muscle loss (VML)
injury model in masseter muscles demonstrated that local
injec�on of SV pep�de immediately a�er the injury
increased EMG ac�vi�es recorded from injured muscles
and suppressed ﬁbrosis by the genera�on of scar �ssues
compared with injec�on of PBS or inac�ve form of SV. Inaddi�on, cultured human skeletal muscle precursor cells
containing SV-pep�de promoted the migra�on anddiﬀeren�a�on of myoblasts.

2023

GMP
peptidesynthesis

Nonclinical

2024

2025

2026

2027

2028

Estimation of efficacy
Safety evaluation and pharmacokinetics
Manufacturing process, quality control
Basic research (biological and physiological )Animal testing
ADME discovery screening research(pharmacodynamics, pharmacokinetics, toxicity test)
Preparation of protocol, clinical study

Phase I
Phase II
Phase IIINDAApproval

Osteopontin

VML injury model (masseter M)

H₂N－Local injectionof SV-peptide

Cleavage by thrombin

GRGDSVVYGLR－COOH

Peptide synthesis

In vivo

Satellite cell

In vitro

Myotube cell

Regenerated
muscle fiber

Ser- Val- Val- Tyr- Gly- Leu- Arg

Acceleration of skeletal muscle regenerationSV-peptide has biological effect on the capability ofcell migration and differentiation in myoblasts

SVVYGLR (SV) peptide

SVSV(-)

48 hPost ope
1W

2W

4W8W6W

SV-peptide enhanced temporal recovery of
the muscle activities after injury

SVMyogenin

0hSV(+)

PBS

DAPI

PBS

SV-peptide stimulated production ofmyotube cells in injured muscle

Myoblast

SV-peptide enhanced migration
capability of myoblasts

SV-peptide stimulated in vitro
myoblast to myotube transformations

Target diseases in this project: Skeletal muscle injuries with irreversible motor dysfunc�on in oral and maxillofacial
surgery, trauma, and congenital abnormali�es including orofacial cle�s such as cle� lip and palate. Title of theInven�on: Restora�ve materials for skeletal muscle injury, Patent No. JP 6912117, US 11,077,167 B2 2017-229688. Aimof this project is to iden�fy and develop a new novel pep�de therapeu�cs with small molecule suited for func�onal
regenera�on in skeletal muscle injuries.
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