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

1st Department of Oral and Maxillofacial Surgery,
Graduate School of Dentistry, Osaka University

Professor Susumu TANAKA

Project Outline
Skeletal muscle dysfunction with serious damages caused by injury or surgery, and congenital diseases with
deformed or poorly developed muscular tissue such as cleft palate, conventional treatments including plastic
surgery occasionally fail to obtain an adequate functional recovery. SVVYGLR (SV), 7-amino-acid sequence
derived from osteopontin (SV peptide) has previously demonstrated strong angiogenic activity, enhancement of thesynthesis of collagen type III in myocardial fibrosis and capability for improvement of cardiac function through thedifferentiation of fibroblasts to myofibroblasts. This peptide was also revealed to be easily degraded by peptidase
and show less adverse effects, indicating high biocompatibility. Like myocardium, skeletal muscle is striated, but it
is voluntary, composed of multi-nucleated muscle fibers regenerated by tissue-specific muscle stem cells calledsatellite cells which proliferate and differentiate to form
Development roadmap
mature myoblasts.
Given the potent role of SV peptide on the repair of2022
2023
2024
2025
2026
2027
injured skeletal muscles like myocardium, it might also
Estimation of efficacy
contribute to functional restoration after the injury. Our
GMP
Safety evaluation and pharmacokinetics
peptidepreliminary study using rat volumetric muscle loss
Manufacturing process, quality control
synthesis(VML) injury model in masseter muscles demonstratedBasic research (biological and physiological )that local injection of SV peptide immediately after theAnimal testing
NonADME discovery screening research
injury increased EMG activities recorded from injured
clinical(pharmacodynamics, pharmacokinetics, toxicity test)
muscles and suppressed fibrosis by the generation of
Preparation of protocol, clinical study
scar tissues compared with injection of PBS or inactive
Phase I
form of SV. In addition, cultured human skeletal muscle
Phase II
Phase IIIprecursor cells containing SV-peptide promoted theNDA
migration and differentiation of myoblasts.
Approval

Osteopontin

VML injury model (masseter M)

H₂N－Local injectionof SV-peptide

Cleavage by thrombin

GRGDSVVYGLR－COOH

Peptide synthesis

In vivo

Satellite cell

In vitro

Myoblast

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
PBSSVPBSSVSV(-)

48 h

Post ope
1W
SV-peptide stimulated production ofmyotube cells in injured muscleMyogenin

0hSV(+)
SV(-)

DAPI

SV(+)

2W

4W

8W

6W

SV-peptide enhanced temporal recovery ofthe muscle activities after injury

SV-peptide enhanced migration
capability of myoblasts

SV-peptide stimulated invitro myoblast to myotube
transformations

Target diseases in this project: Skeletal muscle injuries with irreversible motor dysfunction in oral andmaxillofacial surgery, trauma, and congenital abnormalities including orofacial clefts such as cleft lip andpalate. Title of the Invention: Restorative materials for skeletal muscle injury, Patent No. JP 6912117, US
11,077,167 B2 2017-229688. Aim of this project is to identify and develop a new novel peptide therapeutics
with small molecule suited for functional regeneration in skeletal muscle injuries.
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