Pharmaceutical Research

, Volume 28, Issue 11, pp 2669–2679

Novel Therapies Targeting Inner Mitochondrial Membrane—From Discovery to Clinical Development

Expert Review

DOI: 10.1007/s11095-011-0476-8

Cite this article as:
Szeto, H.H. & Schiller, P.W. Pharm Res (2011) 28: 2669. doi:10.1007/s11095-011-0476-8
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ABSTRACT

Mitochondrial oxidative stress and dysfunction have been implicated in the aging process and in numerous chronic diseases. The need for therapies that can protect and/or improve mitochondrial function is obvious. However, the development of mitoprotective drugs has been hampered by a number of challenges, and there are at present no approved therapies for mitochondrial dysfunction. This article describes the original discovery, preclinical development, and clinical development of a novel class of small peptide molecules that selectively target the inner mitochondrial membrane and protect mitochondrial function. These compounds have the potential to be a paradigm-shifting approach to the treatment of mitochondrial dysfunction, which underlies many common diseases, including cardiorenal, neurologic, and metabolic disorders.

KEY WORDS

ischemia-reperfusion injury metabolic disorders neurodegenerative diseases oxidative stress Szeto-Schiller peptides 

ABBREVIATIONS

ATP

adenosine triphosphate

BBB

blood-brain barrier

CypD

cyclophilin D

Cyt c

cytochrome c

ETC

electron transport chain

IMM

inner mitochondrial membrane

iv

intravenous

MCAT

overexpression of catalase targeted to mitochondria

MPP+

1-methyl-4-phenylpyridium

MPT

mitochondrial permeability transition

MPTP

1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine

OMM

outer mitochondrial membrane

ROS

reactive oxygen species

sc

subcutaneous

SOD

superoxide dismutase

TPP+

triphenylphosphonium ion

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Department of PharmacologyJoan and Sanford I. Weill Medical College of Cornell UniversityNew YorkUSA
  2. 2.Laboratory of Chemical Biology and Peptide ResearchClinical Research Institute of MontrealMontrealCanada

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